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Abiogenesis, DNA, RNA, and Protein Interaction


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#31 Cyto

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Posted 24 October 2003 - 07:36 PM

Posted ImageNOAA:: Chemical Oceanography:: Hydrothermal Vent Geochemistry::Posted Image

Hydrothermal circulation occurs when seawater penetrates into the ocean crust, becomes heated, reacts with the crustal rock, and rises to the seafloor. Seafloor hydrothermal systems have a major local impact on the chemistry of the ocean that can be measured in hydrothermal plumes. Some hydrothermal tracers (especially helium) can be mapped thousands of kilometers from their hydrothermal sources, and can be used to understand deep ocean circulation. Because hydrothermal circulaton removes some compounds from seawater (e.g. Mg, SO4) and adds many others (He, Mn, Fe, H2, CO2), it is an important process in governing the composition of seawater.


And there are clays at the ocean floor.

GEOL 206.3 Marine Sediments — A summary

#32 Cyto

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Posted 05 November 2003 - 09:57 PM

From sciencenews.org, some articles that should be out already.
Week of Nov. 1, 2003; Vol. 164, No. 18

Ancient atmosphere was productive
New laboratory experiments suggest that extra carbon dioxide in the atmosphere in the era just before the dinosaurs went extinct may have boosted plant productivity to at least three times that found in today’s ecosystems.
Source Page (active)

Clays catalyze life?
Clay minerals at the bottom of the ocean may have played a crucial role in assembling the very first cells on Earth billions of years ago.
Sources (active)

Click HERE to rent this GENETICS advertising spot to support LongeCity (this will replace the google ad above).

#33 Cyto

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Posted 28 November 2003 - 06:26 AM

A New Hypothesis On The Origin Of 'Junk' DNA

T he hypothesis explains a mysterious genetic difference between bacteria and eukaryotes, a giant group of organisms that includes animals, plants, fungi, algae and other protists. Bacteria tend to have extremely lean genomes; their genes barely fit into them, without much genetic material left over. Eukaryotic genomes are a complex mixture of useful genes and useless ("junk") DNA jammed haphazardly between genes and even within them.

"The evolution of genomic complexity is inevitable," said IUB biologist Michael Lynch, who led the study. "It's just that in bacteria, there is a pressure against it -- natural selection -- which works more efficiently when population sizes are big. Eukaryotes have much smaller population sizes compared to bacteria, and we believe this is the main reason junk DNA sequences are still with us."

Junk DNA dominates eukaryotic chromosomes. The chromosomal space taken up by just 30 human genes and the DNA within and between those genes could easily accommodate whole bacterial genomes containing 3,000 or 4,000 genes, Lynch said. While some of what geneticists have called junk DNA is turning out to be not so junky after all, Lynch said a substantial fraction of such genetic material probably deserves the name.

Genetic mutations occur in all organisms. But since large-scale mutations -- such as the random insertion of large DNA sequences within or between genes -- are almost always bad for an organism, Lynch and University of Oregon computer scientist John Conery suggest the only way junk DNA can survive the streamlining force of natural selection is if natural selection's potency is weakened.

When populations get small, Lynch explained, natural selection becomes less efficient, which makes it possible for extraneous genetic sequences to creep into populations by mutation and stay there. In larger populations, disadvantageous mutations vanish quickly.

Most experts believe that the first eukaryotes, which were probably single-celled, appeared on Earth about 2.5 billion years ago. Multicellular eukaryotes are generally believed to have evolved about 700 million years ago. If Lynch's and Conery's explanation of why bacterial and eukaryotic genomes are so different is true, it provides new insights into the genomic characteristics of Earth's first single-celled and multicellular eukaryotes.

A general rule in nature is that the bigger the species, the less populous it is. With a few exceptions, eukaryotic cells are so big that they make most bacteria look like barnacles on the side of a dinghy. If the first eukaryotes were larger than their bacterial ancestors, as Lynch believes, then their population sizes probably went down. This decrease in eukaryote population sizes is why a burgeoning of large-scale mutations survived natural selection in the first single-celled and multicellular eukaryotes, according to Lynch and Conery.

To estimate long-term population sizes of 50 or so species for which extensive genomic data was available, Lynch and Conery examined "silent-site" mutations. Silent-site mutations are single nucleotide changes within genes that don't affect the gene product, which is a protein. Because of their unique characteristics, silent-site mutations can't be significantly influenced by natural selection. The researchers were able to calculate rough estimates of the species' long-term population sizes by assessing variation in the species' silent-site nucleotides.

Of the original group of sampled organisms, Lynch and Conery selected a subset of about 30 and calculated, for each organism, the number of genes per total genome size as well as the longevity of gene duplications per total genome size. They also calculated the approximate amount of each organism's genome taken up by DNA sequences that do not contain genes.

The researchers found that a consistent pattern emerged when genomic characteristics of bacteria and various eukaryotes were plotted against the species' total genome sizes. Bigger species, such as salmon, humans and mice, tended to have small, long-term population sizes, more genes, more junk DNA and longer-lived gene duplications. Almost without exception, the species found to have large, long-term population sizes, fewer genes, less junk DNA and shorter-lived gene duplications were bacteria.

The data suggest it is genetic drift (an evolutionary force whose main component is randomness), not natural selection, that preserves junk DNA and other extraneous genetic sequences in organisms. When population sizes are large, drift is usually overpowered by natural selection, but when population sizes are small, drift may actually supersede natural selection as the dominant evolutionary force, making it possible for weakly disadvantageous DNA sequences to accumulate.

"As more organisms' genomes are sequenced, we will continue to look at whether our model is upheld," Lynch said.


Source: Indiana University

#34 kevin

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Posted 18 March 2004 - 08:32 PM

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Link:
http://www.biomedcen...ews/20040318/01
Date: 03-18-04
Author: Cathy Holding
Source: http://www.biomedcentral.com
Title: Riboswitch ribozyme - Gene expression controlled directly by metabolites binding to RNA
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Riboswitch ribozyme - Gene expression controlled directly by metabolites binding to RNA

So far, all repressor molecules that have been characterized are proteins. But a new study in the March 18 Nature describes a novel catalytic RNA that controls its own gene expression. These findings, say the study's authors, point to the gene control mechanisms employed by primitive organisms and suggest that modern cells retain some of these systems.

All metabolite-binding riboswitches so far discovered induce a structural change in the messenger RNA that controls gene expression by straightforward mechanisms, said Ron Breaker, associate professor in the Department of Molecular, Cellular, and Developmental Biology at Yale and senior author on the study. “The glmS ribozyme is the first riboswitch to be found that works by cutting the messenger RNA,” Breaker said in an E-mail to The Scientist.

“A ribozyme in the RNA actually carries out the chemical cleavage of that RNA and thereby makes it useless,” said David M.J. Lilley, director of Cancer Research UK's Nucleic Acid Structure Research Group at the University of Dundee. “So, one huge difference is it only becomes activated [to cut itself] by the binding of a small molecule—in other words, this glucosamine 6 phosphate,” said Lilley, who was not involved in the study.

“If it's the first member of a very large family of riboswitch ribozymes, then that shows that ribozymes are participating in genetic control as opposed to gene expression,” said Scott K. Silverman from the Department of Chemistry, University of Illinois at Urbana-Champaign. A riboswitch that is a ribozyme offers one mechanism by which encoded information, in the form of genes, could be regulated by RNA—one of the basic underlying requirements for an RNA world.

“The newly discovered molecular switch [the riboswitch] involves an RNA molecule with enzymatic activity [the ribozyme],” explained Thomas R. Cech, from the Howard Hughes Medical Institute in an accompanying News and Views article. The ribozyme is upstream of the glmS mRNA, which generates the small sugar glucosamine-6-phosphate, involved in cell wall biosynthesis.

In the postulated “RNA world” of 3.6 billion years ago, RNA was able to both store information and carry out chemical reactions, and life forms would not have used DNA or proteins, said Lilley. “You can get a very simple but crude genetic system that can evolve, and so you can build more complexity,” he said.

It was possible to imagine that these RNAs started recruiting extra molecules, rather as enzymes use cofactors in the modern world, he added. “The advantages of amino acids were such that they kind of took over, and probably the finest creation of this RNA world was, in fact, proteins.” Once there, it was possible very rapidly to get up to a modern, protein-based world, said Lilley.

Eukaryotic gene control systems typically are far more complex than metabolite-triggered self-destruction of mRNAs, said Breaker, but this self-cutting ribozyme may persist today because the ribozyme is simply very good at what it does: it recognizes its target metabolite with great precision.

“The RNA fragment produced when the ribozyme cleaves is also highly conserved,” he said, suggesting that the ribozyme is needed to release this small RNA as well as shut down expression of the glmS mRNA.

“Perhaps the complexity that protein factors offer is the key to building complex multicellular organisms, and this might be one of the reasons why organisms of the RNA world were driven to extinction,“ Breaker said.

Links for this article
W. Winkler et al., “Control of gene expression by a natural metabolite-responsive ribozyme,” Nature, 428:281-286, March 18, 2004.
http://www.nature.com/

Ronald Breaker
http://www.yale.edu/...ker/breaker.htm

David M.J. Lilley
http://www.dundee.ac...LSBDIV1dmjl.htm

Scott K. Silverman
http://www.life.uiuc..._silverman.html

Thomas R. Cech
http://www.hhmi.org/...ators/cech.html

T.R. Cech, “RNA finds a simpler way,” Nature, 428:263-264, March 18, 2004.
http://www.nature.com/

#35 Cyto

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Posted 31 March 2004 - 10:25 PM

Molecular midwives hold clues to the origin of life :)

Adding a small molecule, dubbed a "molecular midwife," researchers increased the rate of DNA formation in a chemical reaction 1,000 fold over a similar reaction lacking a midwife. The discovery is an important step in the effort to trace the evolution of life back to the earliest self-replicating molecules. The results are reported in the April 2 edition of the German chemistry journal Angewandte Chemie.

Hud first proposed the idea of a molecular midwife in a paper published in the Journal of Theoretical Biology in 2000, along with co-author Frank Anet, professor emeritus at UCLA. The problem they said was this. When you throw all the components needed to make RNA into a soup, the individual components do not spontaneously form RNA. But there may have been other molecules present at the dawn of life that would have increased the chances RNA would form. If this were true, then it would provide a missing link in the evolution of life's earliest molecules.

Hud and Anet, along with Georgia Tech students Swapan Jain and Christopher Stahle, tested this idea by using the molecule proflavin to aid the chemical synthesis of DNA (DNA is chemically very similar to RNA and its synthetic reagents were more readily adapted for their test reaction). They found that proflavin accelerates by 1,000 times the rate at which two short DNA molecules become connected into a larger DNA molecule.

So if RNA came first, how did it get here? Hud's theory is this. Much like a ladder with one side lopped off, RNA is made up of a long chain of sugars and phosphate groups - known as a polymer backbone - forming one side of the ladder and with four different types of molecules - known as bases - forming the rungs. In the beginning, individual bases may have been connected to sugars and phosphate groups to form molecules called nucleotides. It's well known that left to their own devices, the bases of nucleotides won't bond with each other with any great frequency, as they do in the well-known double helix of DNA. But if, Hud and company propose, a molecular midwife such as proflavin were present, it would create a platform on which two bases could stack and pair with each other. As pairs of nucleotide bases stack with interspersed midwives, in a Dagwood-style sandwich, the nucleotides can stitch together to form molecules such as RNA or DNA. Once these molecules are long enough, the midwives can float away and the bases would remain paired in a double helix, or separate to promote the formation of more RNA molecules, depending upon solution conditions.

"Most recently we have demonstrated in our laboratory that proflavin can also work as a molecular midwife for RNA formation, as well as DNA," said Hud. "We are very excited about these results. However, our ultimate goal is to achieve a self-replicating molecular system that is capable of evolving." That development, he added, is still several years away.



#36 Cyto

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Posted 23 April 2004 - 03:30 AM

Discovery offers clues to origin of life

A new discovery of microbial activity in 3.5 billion-year-old volcanic rock and one of earth's earliest signs of geological existence sheds new light on the antiquity of life, says University of Alberta researchers who are part of a team that made the groundbreaking finding.
"People have been looking for signs of early bacteria for the last 50 years," said Dr. Karlis Muehlenbachs, from the U of A's Faculty of Science and an author on the paper just published in the journal Science. "A variety have claimed they've seen it and subsequently been challenged as being flawed. We are suggesting that we have clear evidence of life prospering in an environment where no one else has bothered to look."

The research team, also made up of Drs. Harald Furnes from the University of Bergen in Norway, Neil Banerjee from the U of A, Hubert Staudigel from the University of California and Maarten de Wit from the University of Cape Town, studied samples of pillow lava taken from the Mesoarchean Barberton Greenstone Belt in South Africa. They found mineralized tubes that were formed in the pillow lava, suggesting microbes colonized basaltic glass of the early oceanic crust, much in the same way as they do modern volcanic glass.

This evidence of life in the basaltic glass on the seafloor comes in the form of textures produced by microbes as they dissolve the glass, said Banerjee. "These textures include channels or tubes produced by the microbe as it tunnels through the glass, possibly using the glass as a source of nutrients," he said. "We have also found traces of carbon, nitrogen, phosphorous and potassium-all essential to life-as well as DNA associated with the microbial alternation textures in the recent basaltic glass samples."

The team then compared its $3.5 billion-year-old samples to the modern pillow lava on the seafloor using several sophisticated tests and was able to find much evidence of life. To date the microbial activity, the team compared the relationship between the tubular structures and the metamorphic mineral growth.

"On the microscopic level, we see that during metamorphism, the new minerals cross cut the preserved biological features," said Muehlenbachs. "This means that the biological features pre date the metamorphism, leading to the conclusion that the microbes were attacking the glass 3.48 billion years ago-very soon after the glass chilled and lasting a few million years, perhaps until the usual geological processes buried and cooked them."

Despite challenges to previous research claiming evidence of life activity, this research team is certain its evidence is solid. "In other discoveries, there has been much discussion and argument about the rock type and where it came from," said Muehlenbachs. "Everyone agrees our rock is from the sea floor-that's a sure thing. Ultimately that leads to the question of where did life start and where did it originate. And we could argue fairly effectively that maybe there is a link with the origin of life in our work."

Another interesting aspect to the research, said Muehlenbachs, is that the rock type they studied is the same as on the surface of Mars. "Martian rocks would also have glass that would retain a record of life activity-we could learn a lot from them as well."



#37 Lazarus Long

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Posted 29 April 2004 - 03:21 PM

And for those that say it will never be done, here we are a major step closer to making life in a test tube.

http://www.nature.co...6/040426-5.html
Posted Image
Mineral brew grows 'cells'
A mixture of simple chemicals produces fungus-like structure.
28 April 2004
PHILIP BALL
© Maselko / Strizhak / ACS
Posted Image
How to make a ‘mineral fungus'

It is an experiment you could do in a school chemistry lab. But it produces weird growths that, although made purely from inorganic materials, share some of the characteristics of living organisms.

Most chemical mixtures quickly settle into an unchanging state. So the fact that dynamic cell-like structures can arise spontaneously from a simple mixture is a surprise, says Jerzy Maselko of the University of Alaska in Anchorage and Peter Strizhak of the Institute of Physical Chemistry in Kiev, Ukraine, who made the discovery1.

Understanding how this happens could give us clues about how life may have arisen on Earth, or even other planets, where the blends of chemicals present might be quite different from that of the early Earth.


Full flow

Maselko and Strizhak mixed calcium chloride, sodium carbonate, copper chloride, sodium iodide, hydrogen peroxide and starch (see box). They found a fungus-like, soft membrane grows out of the mixture, enclosing a hollow cavity up to 1 cm across. Chemicals diffuse through this membrane, react inside the cavity, and then diffuse out, creating swirling clouds of violet liquid in the green base solution.

Rather than reaching equilibrium, this process persists. The reactions, say the researchers, are reminiscent of the way living cells sustain themselves, driven from equilibrium by the flow of chemicals and energy across their membranes.

Maselko and Strizhak even saw a kind of replication in their chemical brew. Sometimes the cell structures grew into forms with several lobes, or sprouted buds that split off from the parent membrane.

But although they look impressive, can these structures tell us anything about the origin of true life-forms? It seems the answer might be yes, because the differences between the two processes are not as fundamental as one might assume.

Graham Cairns-Smith, a chemist at the University of Glasgow in Scotland, has speculated for many years that life on our planet may not have started with organic (carbon-based) molecules. He suggests life may have begun with inorganic ingredients, such as clay minerals that can carry heritable information in the stacking sequence of their sheets of atoms. Such 'clay organisms' might be able to replicate, Cairns-Smith argues.

Maselko is keen to follow up his discovery to see just how far the parallels with life run. "This is only the beginning," he says. "We will see many other systems like this. The next step will be to get these systems to evolve."


References
Maselko, J. & Strizhak, P. Journal of Physical Chemistry B, 108, 4937 - 4939, doi:10.1021/jp036417j (2004). |Article|

© Nature News Service / Macmillan Magazines Ltd 2004

#38 Cyto

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Posted 07 May 2004 - 03:07 AM

Analysis Uncovers Critical Stretches of Human Genome

Hundreds of stretches of DNA may be so critical to life's machinery that they have been “ultra-conserved” throughout hundreds of millions of years of evolution. Researchers have found precisely the same sequences in the genomes of humans, rats, and mice; sequences that are 95 to 99 percent identical to these can be found in the chicken and dog genomes, as well.

Most of these ultra-conserved regions do not appear to code for proteins, but may instead play a regulatory role. Evolutionary theory suggests these sequences may be so central to mammalian biology that even small changes in them would compromise the animal's fitness.

“It's extraordinarily exciting to think that there are these ultra-conserved elements, so many of which are near well-studied genes, that weren't noticed by the scientific community before because we didn't have the comparative data that highlighted these regions,” said Haussler. “The real credit goes to the prodigious efforts in sequencing these multiple genomes, which have given us this tremendous opportunity, opening our eyes to these very unusual genomic elements,” he said.

According to Haussler, the researchers were launched on their analysis when initial studies hinted at major regions of conserved DNA sequences. “When we had compared the human and mouse genomes, we found that about five percent of each of these showed some kind of evolutionary selection that partially preserved the sequence,” he said. “We got excited about this because only about 1.5 percent of the human genome codes for protein. So five percent was about three times as much as one might expect from the standard model of the genome, in which it basically codes for proteins, with a little bit of regulatory information on the side, and the rest is nonfunctional or “junk” DNA.

“These initial findings suggested that quite a lot of the genome was performing some kind of regulatory or structural role - doing something important other than coding for proteins,” said Haussler.

When the rat genome sequence became available, the researchers decided to search for the most extreme cases of conservation among the three mammalian species. They looked for long stretches of DNA, at least 200 base-pairs in a row, that were identical among humans, rats and mice. Statistically, the likelihood that a sequence of this length would appear unchanged among all three genomes by chance was infinitesimally small.

The results, said Haussler, were startling. The comparison of the three genomes revealed 481 such elements that they called “ultra-conserved.” “What really surprised us was that the regions of conservation stretched over so many bases. We found regions of up to nearly 800 bases where there were absolutely no changes among human, mouse and rat.”

Although 111 of these ultra-conserved elements overlapped with genes known to code for proteins, 256 showed no evidence that they overlap genes, and another 114 appeared inconclusively related to genes. In the 111 that overlapped genes, relatively small portions were actually in coding regions. Many were either in untranslated regions of the gene's messenger RNA transcript or in regions that are spliced out before the message is translated into protein.

Ultra-conserved regions were often found overlapping genes that specified proteins involved in binding RNA and regulating its splicing. “One of these genes is known to regulate its own splicing so as to either include or not include an ultra-conserved section, depending on conditions. There is also evidence for regulatory `crosstalk' with another member of the same gene family at this point. We may want to investigate further to see if these ultra-conserved elements that overlap RNA-processing genes are part self-regulating networks of RNA-processing activity,” said Haussler.

As to the function of the conserved regions that don't overlap genes, Haussler said, “there are hints that they may be involved in regulating transcription, but if so, it's a complete mystery how they work. What people find most interesting and exciting about these results is that they raise more questions than they answer.”

For example, said Haussler, the many conserved elements that are not in genes still tend to cluster in groups at certain places on the chromosomes. These clusters are often next to or surrounding genes that are known to play a role in regulating the activity of other genes in embryonic development. The conserved elements in the cluster can be up to a million bases away from the gene, however. “The fact that conserved elements are hanging around the most important development genes suggests that they have some role in regulating the process of development and differentiation,” said Haussler, “even though they are often far away from the gene itself.”

“What really surprised us was that when we included the chicken genome in this comparison, we found that nearly all these regions still showed amazingly high levels of conservation,” he said. “In 29 cases it was 100%. This, despite the fact that the common ancestor of chickens, rodents, and humans is thought to have lived about 300 million years ago,” he said.

However, the researchers found these regions to be significantly less conserved in the genome of the fish called fugu. And when they extended their comparisons to the even more ancient genomes of the sea squirt, fruit fly and roundworm, they found very little evidence of these conserved elements. The sea squirt exhibits a simple spinal cord early in its life cycle, and so it is more closely related to vertebrates than are flies or worms.

“The most exciting thing for me is that the ultra-conserved regions we have identified do represent evolutionary innovations that must have happened sometime during vertebrate development, because we see such large pieces that no longer match in fish, and almost nothing in sea squirt. They must have evolved rather rapidly while our ancestors were still in the ocean, with some further evolution when animals first started to colonize land; after that they must have essentially frozen evolutionarily.

“This suggests that these were foundational innovations that were very important to the species, and since the conserved elements are different from one another, that each one was important in some particular way. It is possible that further innovations in other interacting elements created so many dependencies that these foundational elements couldn't be mutated any more without disrupting something vital,” said Haussler.

Besides the fact that the purpose of the non-coding ultra-conserved elements remains unknown, said Haussler, the researchers also do not understand the molecular mechanism of their action that requires them to be so faithfully preserved. “A major question is what molecular mechanism would demand such a relentless conservation over hundreds of bases,” he said. “There is still the possibility that these regions are not so vital to the function of the organism, but in fact change very slowly for some other reason, such as lack of susceptibility to mutation, or “hyper-repair.” But it is even harder to imagine a mechanism for that.”



#39 Cyto

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Posted 12 May 2004 - 04:16 AM

22-amino acid bacterium created by Scripps scientists

A team of investigators at The Scripps Research Institute and its Skaggs Institute for Chemical Biology in La Jolla, California has modified a form of the bacterium Escherichia coli to use a 22-amino acid genetic code.
"We have demonstrated the simultaneous incorporation of two unnatural amino acids into the same polypeptide," says Professor Peter G. Schultz, Ph.D., who holds the Scripps Family Chair in Chemistry at Scripps Research. "Now that we know the genetic code is amenable to expansion to 22 amino acids, the next question is, how far can we take it?"

In an upcoming issue of the journal Proceedings of the National Academy of Sciences, the team describes how they engineered this modified form of E. coli to make myoglobin proteins with 22 amino acids -- incorporating the unnatural amino acids O-methyl-L-tyrosine and L-homoglutamine in addition to the naturally occurring 20.

Scientists have for years created proteins with such unnatural amino acids in the laboratory, but until Schultz and his colleagues began their work in this field several years ago, nobody had ever found a way to get organisms to add unnatural amino acids into their genetic code. Earlier studies by Schultz's group described the incorporation of a number of single unnatural amino acids with a variety of uses in chemistry and biology into E. coli and into the yeast Saccharomyces cerevisiae.

This latest result is a boon because it demonstrates that multiple unnatural amino acids can be added to the genetic code of a single modified organism. This proof-of-principle opens the door for making proteins within the context of living cells with three, four, or more additional amino acids at once.

The article, "A twenty-two amino acid bacterium with a functional quadruplet codon" is authored by J. Christopher Anderson, Ning Wu, Stephen W. Santoro, Vishva Lakshman, David S. King, and Peter G. Schultz and will be posted online during the week of May 10-16, 2004 by the journal Proceedings of the National Academy of Sciences. See: http://www.pnas.org/...ct/0401517101v1. The article will appear in print later this year.

This work was supported by the Department of Energy and the Skaggs Institute for Research. Individual scientists involved in this study were sponsored through a National Science Foundation Predoctoral Fellowship, a Canadian Institutes of Health Research fellowship, and a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund.

Why Expand the Genetic Code?

Life as we know it is composed, at the molecular level, of the same basic building blocks. For instance, all life forms on earth use the same four nucleotides to make DNA. And with few exceptions, all known forms of life use the same common 20 amino acids -- and only those 20 -- to make proteins.

The question is why did life stop with 20 and why these particular 20?

While the answer to that question may be elusive, the 20-amino acid barrier is far from absolute. In some rare instances, in fact, certain organisms have evolved the ability to use the unusual amino acids selenocysteine and pyrrolysine -- slightly modified versions of the amino acids cysteine and lysine.

These rare exceptions aside, scientists have often looked for ways to incorporate unnatural amino acids into proteins in the test tube and in the context of living cells because such novel proteins are of great utility for basic biomedical research. They provide a powerful tool for studying and controlling the biological processes that form the basis for some of the most intriguing problems in modern biophysics and cell biology, like signal transduction, protein trafficking in the cell, protein folding, and protein–protein interactions.

For example, there are novel amino acids that contain fluorescent groups that can be used to site-specifically label proteins with small fluorescent tags and observe them in vivo. This is particularly useful now that the human genome has been solved and scientists are now turning their attention to what these genes are doing inside cells.

Other unnatural amino acids contain photoaffinity labels and other "crosslinkers" that could be used for trapping protein–protein interactions by forcing interacting proteins to be covalently attached to one another. Purifying these linked proteins would allow scientists to see what proteins interact with in living cells -- even those with weak interactions that are difficult to detect by current methods.

Unnatural amino acids are also important in medicine, and many proteins used therapeutically need to be modified with chemical groups such as polymers, crosslinking agents, and cytotoxic molecules. Last year, Schultz and his Scripps Research colleagues also showed that glycosylated amino acids could be incorporated site-specifically to make glycosylated proteins -- an important step in the preparation of some medicines.

Novel hydrophobic amino acids, heavy metal-binding amino acids, and amino acids that contain spin labels could be useful for probing the structures of proteins into which they are inserted. And unusual amino acids that contain chemical moieties like "keto" groups, which are like LEGO blocks, could be used to attach other chemicals such as sugar molecules, which would be relevant to the production of therapeutic proteins.

Combining Amber Suppression with Frame Shift Suppression

Schultz and his colleagues succeeded in making the 22-amino acid E. coli by exploiting the redundancy of the genetic code. When a protein is expressed, an enzyme reads the DNA bases of a gene (A, G, C, and T), and transcribes them into RNA (A, G, C, and U). This so-called "messenger RNA" is then translated by another protein-RNA complex, called the ribosome, into a protein. The ribosome requires the help of transfer RNA molecules (tRNA) that have been "loaded" with an amino acid, and that requires the help of a "loading" enzyme.

Each tRNA recognizes one specific three-base combination, or "codon," on the mRNA and gets loaded with only the one amino acid that is specific for that codon.

During protein synthesis, the tRNA specific for the next codon on the mRNA comes in loaded with the right amino acid, and the ribosome grabs the amino acid and attaches it to the growing protein chain.

The redundancy of the genetic code comes from the fact that there are more codons than there are amino acids used. In fact, there are 4x4x4 = 64 different possible ways to make a codon -- or any three-digit combination of four letters in the mRNA (UAG, ACG, UCC, etc.). With only 20 amino acids used by the organisms, not all of the codons are theoretically necessary.

But nature uses them anyway. Several of the 64 codons are redundant, coding for the same amino acid, and three of them are nonsense codons -- they don't code for any amino acid at all.

These nonsense codons are useful because normally when a ribosome that is synthesizing a protein reaches a nonsense codon, the ribosome dissociates from the mRNA and synthesis stops. Hence, nonsense codons are also referred to as "stop" codons. One of these, the amber stop codon UAG, played an important role in Schultz's research.

Schultz and his colleagues knew that if they could provide their cells with a tRNA molecule that recognizes UAG and also provide them with a synthetase "loading" enzyme that loaded the tRNA with an unnatural amino acid, the scientists would have a way to site-specifically insert the unusual amino acid into any protein they wanted.

They needed to find a functionally "orthogonal" pair­a tRNA/synthetase pair that react with each other but not with endogenous E. coli pairs. So they devised a methodology to evolve the specificity of the orthogonal synthetase to selectively accept unnatural amino acids.

Starting with a tRNA/synthetase pair from the organism Methanococcus jannaschii, they created a library of E.coli cells, each encoding a mutant M. jannaschi synthetase, and they changed its specificity so that it could be use to recognize the unnatural amino acid O-methyl-L-tyrosine.

To do this, they devised a positive selection whereby only the cells that load the orthogonal tRNA with any amino acid would survive. Then they designed a negative selection whereby any cell that recognizes UAG using a tRNA loaded with anything other than O-methyl-L-tyrosine dies.

In so doing, they found their orthogonal synthetase mutants that load the orthogonal tRNA with only the desired unnatural amino acid. When a ribosome reading an mRNA within the E. coli cells encounters UAG, it inserts the unnatural amino acid O-methyl-L-tyrosine.

Furthermore, any codon in an mRNA that is switched to UAG will encode for the new amino acid in that place, giving Schultz and his colleagues a way to site-specifically incorporate novel amino acids into proteins expressed by the E. coli.

Similarly, Schultz and his colleagues made an engineered tRNA/synthetase orthogonal pair from the polar archean organism Pyrococcus horikoshii that recognizes the four-base codon AGGA.

The tRNA has a four-base anticodon loop, and when a ribosome reading an mRNA within the E. coli cells encounter AGGA, it inserts the unnatural amino acid L-homoglutamine at that site.

By placing both of these systems within the same E. coli cell, Schultz and his colleagues have demonstrated, as a proof of principle, that it is technically possible to have mutually orthogonal systems operating at once in the same cell. This opens up the possibility of doing multiple site substitution with additional unnatural amino acids in the future.



#40 kevin

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Posted 12 May 2004 - 04:39 AM

Link: http://www.eurekaler...rbs-1904101.php

Here's a similar 'novel amino acid' article from a few years back...




Public release date: 19-Apr-2001

Contact: Robin B. Goldsmith
rgoldsmi@scripps.edu
858-784-8134
Scripps Research Institute

Simultaneous reports by scientists at the Scripps Research Institute show how they made bacteria do what nature doesn't
La Jolla, CA, April 20, 2001 – Scientists at The Skaggs Institute for Chemical Biology at The Scripps Research Institute (TSRI), have published two separate papers in the current issue of the journal Science in which they describe two different ways of engineering bacterial cells to encode "unnatural" proteins.

These proteins differ from those produced by other living organisms because they incorporate novel amino acids, the subunit molecules of which proteins are composed.

Both of these methods could provide powerful new mechanisms for studying protein and cellular functions, because they are proof-of-principal that bacterial strains can be made to incorporate novel amino acids into proteins. In addition, they could enable scientists to envision the possibility of engineering completely new proteins.

According to TSRI President Richard A. Lerner, M.D., "One of the holy grails of modern genetics is the extension of the genetic code to increase the ability of proteins to perform new chemical tasks. We at The Skaggs Institute of TSRI are extremely proud to have accomplished this by two separate routes."

Principal Investigators Peter Schultz, Ph.D., Scripps Family Chair, The Skaggs Institute and Department of Chemistry; and Paul Schimmel, Ph.D., Ernest and Jean Hahn Professor and Chair, The Skaggs Institute, and Departments of Molecular Biology and Chemistry, led the two separate efforts.

The research article, "Enlarging the Amino Acid Set of Escherichia coli by Infiltrating the Valine Coding Pathway," is authored by Volker Döring, Henning D. Mootz, Leslie A. Nangle, Tamara L. Hendrickson, Valérie de Crécy-Lagard, Paul Schimmel, and Philippe Marlière.

The research article, "Expanding the Genetic Code of Escherichia coli," is authored by Lei Wang, Ansgar Brock, Brad Herberich, and Peter G. Schultz.

Encoding proteins from DNA is one of the most fundamental requirements for life, since proteins do much of the microscopic work of the cell and make up a large part of the physical structure of cells and tissue.

When a protein is expressed, an enzyme reads the DNA bases of a gene (A,G,C, and T), and transcribes them into RNA (A, G, C, and U). This so-called "message RNA" is translated by another enzyme, called the ribosome, into a protein, which is a chain of amino acids. For every codon on the mRNA—every three bases—the ribosome attaches another amino acid to the chain.

But even though there are 4x4x4 = 64 different codons (UAG, ACG, UTC, etc.) there are only 20 amino acids that all organisms use to produce proteins. One of the great unanswered questions of evolutionary biology is why there are only 20.

Some of the 64 codons are redundant, with several coding for the same amino acid, and a few of them are nonsense codons—they don't code for anything at all.

Schultz and his colleagues have developed a general method to make the bacterium Escherichia coli incorporate novel amino acids site-specifically.

Their approach starts with generating an orthogonal transfer RNA/synthetase pair, which does not interact with other pairs existing in E. coli.

Then the orthogonal synthetase was engineered so that it charges the orthogonal tRNA with an unnatural amino acid but not any natural amino acids.

The orthogonal tRNA delivers the attached novel amino acid into proteins in response to a UAG codon inserted at any position of interest.

Using this method, they have incorporated O-methyl-L-tyrosine into proteins with purity higher than 99 percent, which is close to the translation fidelity of natural amino acids.

Schimmel and his colleagues used a more general approach, which broadly incorporates the novel amino acid aminobutyrate into proteins where the amino acid valine should go. To do this, they modified the valine tRNA synthetase enzyme.

Using mutagenesis and screening, they were able to find a valine tRNA synthetase with no proofreading mechanism. In this mechanism, another part of the enzyme checks to see if it accidentally attached an aminobutyrate to a tRNA where it should have attached a valine.

Though aminobutyrate and valine are almost identical, the proofreading mechanism is highly specific, allowing fewer that one mistake in 100,000 tries.

But the proofreading mutants are so good at making mistakes that in their paper, Schimmel and his colleagues report that 24 percent of all the valines are randomly replaced with aminobutyrates.

These strange new proteins can then be purified and studied in isolation, or left in vivo and used as a probe to study cellular functions.

Furthermore, proteins with novel amino acids may prove to have enhanced or emergent properties. Having a bacterial expression system will make them trivial to produce on a massive scale.


###
The research was funded by The Skaggs Institute for Research, National Institutes of Health, National Foundation for Cancer Research, and the Office of Navy Research.

(A "Perspectives" piece on this work will be published in Science magazine and is available by contacting Ginger Pinholster, AAAS, 202-326-6440.)

#41 kevin

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Posted 13 May 2004 - 06:58 PM

Link: http://story.news.ya...virus_discovery



Scientists: Virus May Give Link to Life
Wed May 12, 2:44 PM ET
BILLINGS, Mont. - Scientists at Montana State University in Bozeman say they have discovered a heat-loving, acid-dwelling virus that could help provide a link to ancient life on Earth.

The virus found in Yellowstone National Park could help to understand a common ancestor that scientists believe was present before life split into forms such as bacteria, heat-loving organisms and the building blocks that led to plants and animals, researchers said.

"It's a clue that helps you say, `Yeah, there probably was a common ancestor at some point or sets of ancestors,'" said George Rice, one of the MSU scientists who participated in the study. "It's food for thought."

The scientists' discovery was published in the May 3 issue of the Proceedings of the National Academy of Sciences (news - web sites).

Rice began hunting for heat-loving "thermophilic" viruses in Yellowstone five years ago. In 2001, he and others found several apparently unique viruses associated with an organism living near Midway Geyser Basin where temperatures ranged from 158 to 197 degrees Fahrenheit.

"It was basically something living in boiling acid," Rice said.

Although several new viruses were discovered, one in particular caught their eye.

After characterizing the structure and genome of the virus, they found that its protein shell was similar to a bacterial virus and an animal virus. The similarity suggests to the scientists that the three viruses may share a common ancestor that predates the branching off of life forms more than 3 billion years ago.

"This is something that was predicted but hadn't been shown before," Rice said.

For a long time, scientists classified all life forms as plant or animal. That classification system expanded as more life forms were discovered. Eventually, biologists divided life into five kingdoms — plants, animals, bacteria, fungi and protists.

A more recent approach divides life into three domains: bacteria, eukarya — which includes plants, fungi, animals and others — and archaea, which means ancient.

Archaea, similar to bacteria, is likely the least understood of the domains, according to the paper's authors. Archaea may have been among the first forms of life on Earth. Able to thrive in the hot, gaseous and volcanic terrain of early Earth, they could also survive in the very inhospitable geothermal features of the Yellowstone of today.

Now that scientists know the Yellowstone virus's ancient structure seems to span all three domains of life, scientists plan additional studies on its genes to figure out what they tell the virus to do.

"Anywhere there's life, we expect viruses," Young said. "They are the major source of biological material on this planet."

Researchers said the virus and others found at Yellowstone will give researchers a hand in the search for life on other planets, including Mars.

"These bugs are living and doing business in a harsh environment," Rice said. "This may be clues about what to look for."

#42 kevin

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Posted 20 May 2004 - 05:02 AM

Link: http://www.eurekaler...s-ana051904.php

A new form of life? COOL! By all indications in the article, it may just be the link between crystal growth and the RNA world that might explain many missing pieces of the genesis of life itself.



Public release date: 19-May-2004

Contact: Claire Bowles
claire.bowles@rbi.co.uk
44-207-331-2751
New Scientist


Are nanobacteria alive?
A team of doctors has provided the best evidence yet for the existence of a new form of life.
SOME claim they are a new life form responsible for a wide range of diseases, including the calcification of the arteries that afflicts us all as we age. Others say they are simply too small to be living creatures. Now a team of doctors has entered the fray surrounding the existence or otherwise of nanobacteria. After four years' work, the team, based at the Mayo Clinic in Rochester, Minnesota, has come up with some of the best evidence yet that they do exist. Cautiously titled "Evidence of nanobacterial-like structures in human calcified arteries and cardiac valves", the paper by John Lieske and his team describes how they isolated minuscule cell-like structures from diseased human arteries. These particles self-replicated in culture, and could be identified with an antibody and a DNA stain. "The evidence is suggestive," is all Lieske claims. Critics are not convinced. "I just don't think this is real," says Jack Maniloff of the University of Rochester in New York. "It is the cold fusion of microbiology." John Cisar of the National Institutes of Health is equally sceptical. "There are always people who are trying to keep this alive. It's like it is on life-support." The first claims about nanobacteria came from geologists studying tiny cell-like structures in rock slices. But in 1998 the debate took a different twist when Olavi Kajander and Neva Ciftcioglu of the University of Kuopio in Finland claimed to have found nanobacteria, surrounded by a calcium-rich mineral called apatite, in human kidney stones.

Objections were raised immediately. Many of the supposed nanobacteria were less than 100 nanometres across, smaller than many viruses, which cannot replicate independently. Maniloff's work suggests that to contain the DNA and proteins needed to function, a cell must be at least 140 nanometres across. Kajander and Ciftcioglu, however, insisted that they had observed the nanoparticles self-replicating in a culture medium and claimed to have identified a unique DNA sequence. How could this be explained if the cells were not alive, they asked. Cisar has an answer to this. After studying nanoparticles found in saliva, his team published a paper in 2000 claiming that the DNA detected by the Finnish team was a contaminant from a normal bacterium. "It wasn't until we couldn't get any unique nucleic acids that we suddenly realised we were being tricked," he says. The paper also said that what looked liked self-replication was just an unusual process of crystal growth. "This just stopped everything in its tracks," says Virginia Miller, a member of Lieske's team. "It is cited as the gospel to why all the papers by Kajander are rubbish... The debate is very polarised and that has shocked me a bit." Some say the claims of Cisar's team are also fantastic. "They talk about 'self-propagating apatite'," says Jorgen Christoffersen, who studies biomineralisation at the University of Copenhagen in Denmark. "This is scientific nonsense." But scepticism about the claims by the Finnish researchers is heightened by the fact that they have financial interests. The group has set up a company called Nanobac Life Sciences in Tampa, Florida, which sells diagnostic kits for spotting nanobacteria. It is even developing treatments for conditions supposedly caused by them, despite the lack of evidence. None of the Mayo researchers, by contrast, holds any patents related to nanobacteria, Lieske says, nor do they have any financial stake in Nanobac. "We are an independent laboratory and we have provided new evidence," Miller says.

The paper went through seven cycles of revision before it was accepted by the American Journal of Physiology: Heart and Circulatory Physiology last week. "The review process, as painful as it was, forced us to look at the counter-arguments inside out, upside down and back to front, then repeat our experiments," Miller says. So what do they have to show for this effort? The researchers collected samples of calcified aneurysms (bulging blood vessels), arterial plaques and heart valves. They pulped the tissue, then filtered it to remove anything bigger than 200 nanometres and added the filtrate to a sterile medium. After a few weeks, the optical density of the liquid doubled, suggesting particles were self-replicating. Samples from aneurysms caused by a genetic disorder did not do this, nor did the density of the medium change if no filtrate was added. Some of the particles were removed, cleaned of their mineral coating, and then imaged with an electron microscope. This revealed small cell-like structures. This much is just repeating the work of Kajander and Ciftcioglu that has been so widely criticised. But the Mayo team has also come up with further results that are much harder to explain away. When the particles were "grown" in a flask, they absorbed uridine, one of the building blocks of RNA.

This suggests that RNA is being produced in the particles, the team says. However, even apatite crystals alone seemed to absorb some uridine, though not as much as the self-replicating particles. And when the Mayo team doused their tissue samples with an antibody that Nanobac claims binds to a protein unique to nanobacteria, they found it bound to diseased tissue, even when the calcium was washed away, but not to healthy tissue. On one sample of the self-replicating particles, they also compared the sites where the antibody bound with those where a DNA stain bound. "The nanobacteria antibody is binding to the same features that stain for DNA," says Miller. This is not enough for the critics. "What you have is umpteen weak arguments at best," Maniloff says. "This is not proof." One crucial piece of evidence would be finding DNA unique to these particles. "Just because other groups have not been able to identify a unique DNA sequence does not mean it does not exist," Miller says. "It just means the tools weren't right at the time." She says that the Mayo team has managed to isolate RNA and DNA, but she is not yet ready to talk about the results. "We are a conservative group, and that has stood us in good stead." Other scientists are also going after the DNA. Yossef Av-Gay, a microbiologist at the University of British Columbia in Vancouver, Canada, has been asked by Nanobac to work out what makes nanobacteria tick. "These particles are self-replicating, that is without doubt," Av-Gay says. But finding out what is inside them is complicated because they are so small and because the apatite shells absorb contaminants. "The problem is to distinguish between material absorbed from the environment and unique sequences from these organisms." Av-Gay too will say nothing about what his studies have revealed. "The story seems to be gearing towards the idea that these are not bacteria, but maybe a new living form. It is a very interesting story, but you won't get the answer now."


###
Written by Jenny Hogan, Boston

New Scientist issue: 22 May 2004

#43 kevin

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Posted 03 June 2004 - 06:38 AM

Link: http://news.national...cter3.html#main

Growing at ABOVE the boiling point of water must be a difficult trick to pull off.. or is it?



Heat-Loving Microbes Offer Clues to Life's Origins
John Roach
for National Geographic News


Over the past 20 years scientists have warmed up to the idea that the majority of life on our planet lives not on Earth's surface but beneath its crust. The theory has spurred new ideas about life's origins on Earth and where to look for life on other planets.

Earth's crust gets warmer the closer it is to the molten iron-nickel believed to be at our planet's core. One question that scientists who study life beneath Earth's crust face is, at what temperature is it too hot for life to survive?

Since scientists believe Earth at one point was mostly molten, the answer to the question may shed light on how early life could have first evolved on our planet.

"If Earth had to cool to a certain temperature at which life was possible, maybe the high-temperature life could have existed that much sooner," said Derek Lovley, a microbiologist at the University of Massachusetts, Amherst.

Much of this life beneath the crust, which scientists refer to as biomass, are microbes that use hydrogen and minerals like iron to get energy from food sources in the same way that humans use oxygen to obtain energy from our food.

Lovley is at the forefront of research into such microbes. He has discovered dozens of different species, including Strain 121, a microbe that grows at 121° Celsius (250° Fahrenheit)—the highest temperature currently known for life.

The ability to grow at 121° Celsius is significant because for over a century it has been the temperature used to sterilize medical equipment. Scientists thought that such temperatures would kill all life-forms.

"It's kind of a benchmark," Lovley said. "This is like breaking the four-minute mile."

Strain 121, which goes dormant at temperatures below 80° Celsius (176° Fahrenheit), lives in environments known as hydrothermal vents on the ocean floor. The vents spew hydrogen- and mineral-rich hot water from deep in the Earth's crust to the surface.

For several years scientists have known that other microbes survive in and around hydrothermal vents at temperatures above 100° Celsius (212° Fahrenheit). Strain 121 just "opens that window where life can exist a little bit wider," Lovley said.

Jack Farmer, an astrobiologist at Arizona State University in Tempe, said that opening this window for life on Earth expands the potential for life to develop and persist elsewhere in the solar system and beyond.

"As the upper temperature limit for life has increased, new opportunities for habitable environments have opened up, and subsurface hydrothermal environments are among the most important," Farmer said.

"Poor Man's Drill"

John Delaney, a marine geologist at the University of Washington in Seattle, led the expedition that brought to the surface the chunk of hydrothermal vent from which Strain 121 was isolated.

Delaney said that examining such environments gives researchers a snapshot of what life is like deeper in the Earth's crust, where temperatures are higher. "Our way of doing it was a 'poor man's drilling program,'" he said.

The expedition team used a remotely operated submarine to cut out and bring to the surface a chunk of hydrothermal vent from the Juan de Fuca Ridge, which lies about 200 miles (322 kilometers) offshore from Washington's Puget Sound and nearly 1.5 miles (2.4 kilometers) deep in the Pacific Ocean.

The seafloor at the Juan de Fuca Ridge is cold, about 2° Celsius (36° Fahrenheit). But down beneath the seafloor the temperature warms gradually until, eventually, it is scalding hot.

"If you telescope those conditions by having hot water coming out along a fissure it will build a sulfide chimney," Delaney said. "And this sulfide chimney is very cold on the outside—two or three degrees—but on the inside it might be as much as 300° centigrade."

A chunk of one of these chimneys, or hydrothermal vents, is what Delaney and his team brought to the surface.

"We figured we would see different kinds of microbes in the wall as it got to hotter and hotter temperatures, and [that] pretty soon microbes wouldn't be there … [which would] indicate a limit to life under those conditions," he said.

Limits and Origins

Microbes like Strain 121 that live in environments lacking organic carbon are known as archaea, which literally means "ancient." Archaea are genetically different from seemingly similar bacteria, which need organic matter and photosynthesis to survive.

The discovery of Strain 121 bolsters the theory held by some scientists that Earth's first life-forms were archaea that could thrive at high temperature via chemical reactions with hydrogen and iron.

"They appear to be the branches closest to what is the last common ancestor of existing life," Lovley said. "All are hyperthermophiles that live at high temperatures."

Early in Earth's history, according to Delaney, volcanic eruptions occurred on the ocean floor as the planet's core separated from its crust. These eruptions could have allowed the mixing of hydrogen and minerals like iron and sulfur, upon which microbes could thrive.

"That may be one of the paths the origins of life takes," Delaney said. If that's the case, he added, then studying hydrothermal vents is a step in the process of understanding how the dynamics of such a system might work.

And understanding how such a system works on Earth may help in the search for life on other planets.


Farmer, the Arizona State University astrobiologist, said, "At the bottom line, hydrothermal systems were widespread in the early solar system and are thought to still be present in the subsurface of many other solar system objects, like Mars, Europa, and even the interiors of large asteroids."

So perhaps the question for scientists isn't is there life on other planets, but is there life inside them.

#44 Lazarus Long

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Posted 04 June 2004 - 05:37 PM

Here is another tantalizing piece of a puzzle. This find if confirmed helps close the gap on Eukaryotic evolution and the Cambrian explosion. It also suggest an additional reason the two may have been separated by the temporal gap we observe in the fossil record.

It appears the Cambrian explosion begins after the Snowball Event in which the Earth was engulfed in a Super Glacial Epoch that extended the Ice Caps nearly to the equator. The Ice Age may have also inhibited the full break out of multicellular life even though Eukaryotes appear to begin just prior to the Glacial Event.

http://news.bbc.co.u...ure/3776853.stm
Posted Image

Posted Image
The findings are reported by a US-Chinese team in Science magazine.
Fossils hint at early complexity
Science, Friday, 4 June, 2004, 13:18 GMT 14:18 UK
The animals may even have possessed sensory organs
Blob-like fossils dating back about 600 million years may indicate that complex life evolved much earlier on our planet than had been thought, scientists say. The animals are less than a fifth of a millimetre long and have a two-sided body plan previously thought to have existed much later in Earth's history.

These "bilaterians" have what look like mouths and guts, as well as internal and external layers of body tissue.

****

The animals - their scientific name is given as Vernanimalcula guizhouena - even have what look like pits in their outer surface that might have contained sensory organs.

They were discovered in rocks from the Doushantuo Formation, dated to a time researchers now refer to as the Ediacaran Period.

This was a period when scientists think our planet was emerging from a super-glacial event - the so-called "Snowball Earth" which saw giant ice caps stretch almost to the equator.

And it is at least 50 million years before the Cambrian Period, when the fossil record shows there was an explosion of life - a multiplicity of different shapes and sizes.

But the age of V. guizhouena suggests the roots of this complexity are much older than had been thought and the Cambrian explosion may not have been quite the sudden burst scientists had believed.


(excerpts)


Super Glacier Event
http://news.bbc.co.u...tech/159988.stm

http://www.sciencene..._29_98/bob1.htm



Anti-Snowball arguments

http://www.spacedail...iceage-01f.html

http://news.bbc.co.u...and/1857545.stm

#45 chubtoad

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Posted 05 August 2004 - 04:14 AM

http://www.nature.co.../040802-12.html

Decoders target 18 new genomes

Diverse sequences will illuminate human evolution and the tree of life.
What secrets lurk in the African elephant's DNA?
What do the elephant, the armadillo and the slime mould have in common? They are all about to have their genomes sequenced by researchers at the US National Human Genome Research Institute, according to plans unveiled on 4 August. In total, 18 species have been selected; they form an eclectic mix designed to shed light on both the human genome and the evolution of the entire tree of life.

It is the first time that species have been selected for genome sequencing in such numbers. Previous projects, most famously the decoding of the human genome, homed in on a single target organism. The roll-call runs from the gigantic to the microscopic: among the organisms selected are the African savannah elephant, the domestic cat, the nine-banded armadillo and a cadre of moulds, snails and worms.

The new strategy will allow scientists to fill gaps in our knowledge about how genomes evolve and which parts of the human sequence are most crucial, says Mark Guyer, a research director at the institute. "With each new genome that we sequence, we move closer to the goal of finding all the crucial elements of the human genome involved in development, health and disease," he says.



#46 Lazarus Long

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Posted 05 August 2004 - 03:42 PM

In an important announcement purported to be made later today, researchers of the genetics of C Elegans have claimed that the mutation rate required for evolution to occur is happening at well over ten times the rate (possibly over twenty) previously thought to be the standard. This is a highly controversial discovery and demands independent testing but the scientists making the claim are confident their observations will stand up and this will alter our current understanding of selection mechanics drastically.

Here is some of the related research I have found so far.

Genomic mutation rates for lifetime reproductive output and lifespan in Caenorhabditis elegans

Researchers Will Try To Identify Gene Involved In Processing Environmental Cues

Abundance, distribution, and mutation rates of homopolymeric nucleotide runs in the genome of Caenorhabditis elegans

http://homepages.ed....searchpage.html

http://genetics.fase...3abs/f1149C.htm

http://genetics.fase...2003abs/f86.htm

Estimation of spontaneous genome-wide mutation rate

The significance of this finding is that the elements of the genome being studied in C Elegans are pretty much shared by all more complex species including us. If this pans out then Environmental Selection is far more powerful than previous understood and *Intentional Genetic Adaptation* much more possible.

#47 Lazarus Long

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Posted 06 August 2004 - 07:47 PM

Here is more follow up on the issue I raised above. It is an audio clip from NPR's "All Things Considered". Any of you that are currently in the study of biology and/or genetics I would love to see the actual reprints on this if you may share them please.

*************

Evolution, Mutation May Occur Faster than Thought

All Things Considered audio (You need to go to the page to hear the audio as I can't insert JAVA links here)

Aug. 4, 2004

Cancer and evolution both occur when genetic material changes randomly in ways that may be good or bad. A study in Nature magazine this week shows that these changes build up at a much quicker rate than anyone thought. The observation was made in tiny worms, but could revolutionize thinking about all living organisms. NPR's Joe Palca reports.

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Posted 06 August 2004 - 11:26 PM

Hi Lazarus,

The key results of the study* had to do with using a different technique to measure the number of mutations between generations and therefore the rate of mutation, which in the worm is at least is 10 times greater then in previous estimates. It implies that our understanding of mutation rates across all species could be similarly underestimated.

Note the suggestion in the article of how a "stressed" organism may increase its rate of mutation or "evolvability" by modulating mismatch polymerase function and introducing additional errors into the genome. This is my view, is a profound insight as it postulates the existence of variable "evolvability" and links it to the mechanism of DNA repair. Thus inferring the existence of a cellular mechanism of altering DNA repair rate which in turn regulates the level of adaptation based on environmental cues.

When considered in the context of why we seem to have a DNA repair system that allows the accumulation of mutations that ultimately result cell senescence, apoptosis or tumorigenesis, this striking suggestion could become the cornerstone for a unified theory of biology that links the mechanism of evolution to the inevitability of aging and disease.



* High mutation rate and predominance of insertions in the Caenorhabditis elegans nuclear genome
DEE R. DENVER, KRYSTALYNNE MORRIS, MICHAEL LYNCH & W. KELLEY THOMAS
Nature 430, 679–682 (2004); doi:10.1038/nature02697

Edited by Bates, 23 July 2005 - 06:29 PM.


#49 kevin

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Posted 11 October 2004 - 07:39 PM

Link: http://www.biomedcen...ews/20041011/01
Posted Image

This is HUGE IMO.

And here we arrive at a time when heretofore acknowledged 'junk DNA' begins to reveal that it is anything but junk, controlling via the use of 'jumping genes' or transposable elements the earliest stages of development of mice embryos. With the emerging awareness of the importance of gene regulation via RNA and transposable elements we see being revealed increasing dynamic layers of complexity and control of the ectopic process of ESC differentiation. Understanding in these areas is likely to lead to better methods of inducing stem cells to become the tissues we need them to be to regenerate and may provide the clues necessary to discover if humans can be induced to perform as admirably as the 'newt' on the regenerative stage.

I found this article from Scientific American on "The Hidden Genetic Program of Complex Organisms" from this months issue quite interesting. It discusses how increasing complexity in information regulation in DNA rather than in the content of the DNA itself explains for the vast differences between simple organisms and the more complex organisms. This fits in nicely with the general idea the that the exchange of information between entities is likely more important than the structural/physical container of the information itself.



Junk DNA controls embryos
Very early embryonic development may be controlled by random movements of repetitive elements
| By Cathy Holding

Transposable elements (TEs) appear to govern the transition from oocyte to embryo in mice, according to a study in Developmental Cell this week. The paper questions the idea that some of the numerous repetitive TEs present in the genome are just "junk."

Barbara B. Knowles, from the Jackson Laboratory at Bar Harbor, Maine, and her group showed that the maternal transcriptome in mouse eggs and very early cleavage embryos contains an unusually high level of TEs that act as promoters and first exons for numerous RNA molecules, revealing a role as stage-specific alternative promoters for a number of host genes.

"We realized that in one of the two forms [of a gene under study], there was a retrotransposon at this unique time [the egg/embryo transition] integrated in front of it," Knowles told The Scientist. The researchers found that the first 20 amino acids of the gene consisted of not only the controlling element of the retrotransposon but also part of the retrotransposon that was a part of this gene, at its 5' end, which suggested that the TE could change the function of the gene.

To determine the overall pattern of TE expression in full-grown oocytes and preimplantation embryos, the team analyzed the number of repetitive element–expressed sequence tags in cDNA libraries from oocytes and 2–cell stage embryos and blastocysts. "We found that the retrotransposons actually do… regulate the expression of a number of different kinds of genes in the genome," Knowles said.

Normal repressive chromatin structure for these loci is established sequentially during the oocyte-to-embryo transition and preimplantation stages, according to the authors.

Linheng Li, at the Stowers Institute for Medical Research in Kansas, said that the findings may be interesting in relation to chromatin opening and the reprogramming occurring then. During nuclear reprogramming after fertilization, the chromosome is wide open because all previous imprints are wiped out.

"In this case, it seems like a lot of genes are just randomly expressed," Li told The Scientist. "My point is, either TE expression is involved in reprogramming or it is a reflection of the reprogramming that is going on." Li was not involved in the study.

"It's an intriguing mechanism; the question is what does it mean?" said Janet Rossant, a professor at the University of Toronto not involved in the study. "Why does the embryo do that? What's the significance to the embryo? I don't think any of those questions are really answered at this point."

Knowles said she thinks the TEs regulate the expression of genes purely as a byproduct of where they are integrated: "I think that they can randomly integrate at a particular time, and then if they're detrimental, then that's the end of the egg, or the embryo. And if they're beneficial, or neutral, it's possible that they may just stay there forever." Those that the team looked at must have been evolutionarily conserved because some of them can be found in the rat genome, said Knowles.

"I think a lot of 'junk DNA' has a function, and in a weird way it's controlling gene expression," Knowles said.

Links for this article
A. Peaston et al., "Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos", Dev Cell, 7:597-606, October 11, 2004.
http://www.developmentalcell.com/

Barbara B. Knowles
http://www.jax.org/s...ra_knowles.html

Linheng Li
http://www.stowers-i.../labs/lilab.asp

Janet Rossant
http://www.mshri.on....sant/index.html

#50 Lazarus Long

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Posted 12 December 2004 - 07:15 PM

In a separate post under Mitochondrial Aging I have been using a model of Selection that treats sexual reproduction as a modified form of mutagenesis.

One that applies sexual selection to the process of determining the fitness of individual mutation. I think this model is one that is not generally appreciated and should be further developed.

To use a rhetorical and metaphoric device we now have one more example of a *Species as a Race*.

The aspect of *Competition* is shared by all sexually reproducing species even at the level of male gametic production. There are numerous deviations around the norm for adaptation. But most share a long term (female) procreative genetic quality control strategy combined with short term male environmental fitness for survival and quantity of production that I go further than most to suggest is actually representative of a form of mutagenic adaptation through selection that is the bulwark of Group Selection by procreative strategy that applies Individual Fitness Selection so as to incorporate successful mutations into the genome resulting in Convergent Evolution made possible by Individual Divergence reflective of survival fitness for mature mutation.

Sexual reproduction can be seen as making possible Speciation over many generations and is exemplary of a Group Selection model that both preserves the germline while incrementally introducing best case mutation through Individual Selection based on perceived environmental pressure. So again it should be emphasized that:

Individuals Diverge through mutation whose fitness is individually selected for by survival success but Species Converge through long term Group Selection based procreative models with respect to environmental pressure and genomic optimization as the prime determiner of *fitness.*

These are two subtly different measures of fitness as individual fitness due to mortality and a lack of longevity does not necessarily reflect more than one environmental paradigm but the mutagenic process determining long term first divergent and subsequent convergence on new environmental niches must reflect a kind of Group Selection pressure that is at work over may generations and not reflected in the paradigm of individual fitness for any specific environmental niche.

This discussion overlaps the hypothesis I propose here in Mitochondria Aging:
http://www.imminst.o...187

And also needs to be understood with respect to the distinctions between Selection models that are defined as:

Ecological Selection
Directional Selection
Stabilizing Selection
Disruptive Selection

and perhaps can be better understood if you follow through the thought process found and developed in this thread on Evolution:
http://www.imminst.o...628

While for practical reasons I am reluctant to merge these two topics I think a parallel review of the thread titled Evolution Q&A's under the philosophy forum is important a general reference.
http://www.imminst.o...t=0

#51 Lazarus Long

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Posted 19 December 2004 - 12:38 AM

In one of the new PanSpermia theories I found some support for possible sexual mutation and selection for bacterial genetics. I am not posting this because I agree with or favor one theory over another but because this article nicely sums up the prevailing Earth/Mars genesis theories with respect to the possible origins of life on either or both planets.

http://story.news.ya...forearthandmars
Life-Swapping Scenarios for Earth and Mars

Mon Dec 13, 2:34 PM ET  Science - Space.com
Leonard David Senior Space Writer
SPACE.com

Evidence is mounting that the time-weathered red planet was once a warm and water-rich world. And a Mars awash with water gives rise to that globe possibly being fit for habitation in its past - and perhaps a distant dwelling for life today.

As sensor-laden orbiters circle the planet, NASA (news - web sites)'s twin Mars rovers -- Spirit and Opportunity -- have been tooling about and carrying out exhaustive ground studies for nearly a year.

The Opportunity robot at Meridiani Planum, for instance, has found telltale signs that water came and went repeatedly within that stretch of Martian real estate. While that intermittent water at Meridiani Planum is thought to be highly acidic and salty, its ability to sustain life for some period of time cannot be ruled out.

What scientists now see is a Mars different in its first billion years of geologic history than once thought - and conceivably an extraterrestrial address for home-grown life.

Rainfall: From years to decades

Mars is one complex and perplexing world.

That was strikingly evident at the Second Conference on Early Mars: Geologic, Hydrologic, and Climate Evolution and the Implications for Life, held Oct. 11-15 in Jackson Hole, Wyoming. Nearly 140 terrestrial and planetary scientists took part in that seminal meeting hosted by the Lunar and Planetary Institute (LPI), NASA, and NASA's Mars Program Office.

"One of the most significant new findings reported at the meeting was that it appears Mars underwent many of its most important changes much earlier in its history than previously thought," said Steve Clifford, an LPI planetary scientist. That includes core formation, the development of the crustal dichotomy, a rapid decline in geothermal heat flow, and the loss of a planetary magnetic field.

"Surprisingly, all of these events appear to have occurred within the planet's first 50 million to 100 million years of existence," Clifford explained. A related discovery is the potential role played by large impacts during this same period, he said, a topographic record of which is preserved in the ancient cratered highlands and has now also been detected beneath the planet's northern plains.

Clifford said simulations indicate that the very largest of these impacts may have blown away a significant fraction of the early Martian atmosphere. Impacts that produced craters greater than some 60 miles (100 kilometers) in diameter might have affected the climate on a regional and global scale, creating transient environmental conditions capable of sustaining continuous rainfall lasting from years to decades, he said.


Water-rich world

"There now appears to be overwhelming evidence that early Mars was water-rich - and may have possessed standing bodies of water and ice that ranged from large seas to a primordial ocean, perhaps covering a third of the planet," Clifford said.

Supporting evidence ranges from orbital observations of extensive layered terrains within, and possible paleoshorelines surrounding, the northern plains to on-the-spot investigations of the mineralogy and sedimentary record recently discovered by the Opportunity rover in Meridiani Planum.

"The implications of these findings are just beginning to be absorbed by the Mars community, yet they have already substantially revised our understanding of the planet's early evolution. They are sure to be a continued focus of attention as the intensity and scope of Mars exploration increases over the next decade," Clifford observed.

Now mix in recent findings about the origin and range of life here on our own planet.

"Life is incredible and the envelope for what we know about where life can live -- data from planet Earth -- is ever expanding and is far beyond what we might have hypothesized," suggested Lynn Rothschild, a scientist in the Ecosystem Science and Technology Branch of NASA's Ames Research Center, Moffett Field, California.

"There is a difference in perspective between planetary folks and biologists regarding where life might thrive. Organisms don't look for a global average. As a microbe, just give me 100 microliters of liquid water and I am happy. In any case, I certainly don't need an ocean! So think microenvironment," Rothschild advised.


Water and energy for microorganisms

Given the wealth of Mars Exploration Rover (MER) data, the likelihood that life could have existed on Mars -- or still does -- is viewed as more probable according to Carrine Blank, Assistant Professor of Molecular Geobiology in the Department of Earth & Planetary Sciences at Washington University, St. Louis, Missouri.

The MER results indicate that there were both large bodies of liquid water on Mars and there were fluids carrying redox (oxidizing and reducing) gradients through the near surface which resulted in precipitation of the blueberries, Blank told SPACE.com. "Life not only requires liquid water, but it also needs a source of metabolic energy," she added, "and redox gradients are great sources of energy for microorganisms.

Blank said in her mind the really big question is just how long was this liquid water and energy present on the surface of Mars. Be it brief or extended, so goes drawing the life line in the sands of Mars.

"If it was for just a brief time in the geologic history of Mars, then perhaps the potential for life is low," Blank said. "If, on the other hand, it was for an extended period of time, then the potential for life at the surface becomes much higher."

What is needed now, Blank noted, is more information about how widespread sedimentary deposits are on Mars, and then identify age constraints on the presence of liquid water at the surface.


Planet swapping microbes

The idea that the seeds of life hobnob between far-flung celestial localities is known as panspermia.

Could Mars be a domain for both microbes flung off Earth due to asteroid and comet impacts, as well as a planet where a "second genesis" might have also occurred? Furthermore, if this was the case, could external life and made-on-Mars biology co-exist?

"Absolutely," advised Blank, adding yet another scenario: That life originated on Mars and was transferred to the Earth, and then went extinct on Mars.

"At present, there is no geologic evidence that the origin of life occurred on the Earth. So one hypothesis is that the origin could have occurred elsewhere, like Mars, and then transferred to the Earth," Blank suggested. Alternatively, life could have originated on the Earth -- but left no evidence since we don't have any rocks for the first billion years of Earth history -- and then transferred to Mars, she said.

"If life was transferred between the planets, then Martian life, past and present, should have similar characteristics to early Earth life," Blank said. "On the other hand, if there was a second genesis, then life on Mars should be very different than life on Earth, and may in fact be quite difficult to detect or even recognize as lifeparticularly if it has gone extinct!" 


Deepest branches on the tree of life

Meanwhile back on Earth, Blank said that more research is needed to understand whether interplanetary transfer of life could have been possible. In particular, additional work on hyperthermophiles -- microbes that live at very high temperatures and that form the deepest branches on the tree of life -- is required, as they were the early inhabitants of the Earth and therefore were the ones most likely to have been transferred around the solar system by impacts, she said.

"We know very little about the origin of life on the Earthhow it happened, what kind of environment it might have happened in, and how long it look to go from the origin to the last common ancestor of life as we know it - a very complex organism very much like modern life," Blank said. 

Casting her eye back on Mars, Blank also said an unknown is whether conditions on early Mars were similar to what they were like on the early Earth when the origin of life likely happened. 

"If they were similar, then perhaps a 'second genesis' could have been possible on Mars.  Even if conditions were different on Mars, there could still have been a second genesis only with a very different result than what happened on the Earth," Blank stated. "If these different life forms were spread throughout the solar system, then they might have co-existed if they could learn to depend upon each other. If, on the other hand, they were in direct competition for resources, then you might expect that one would 'win' and survive, and the other go extinct," she advised.


War of the worlds?

Jack Farmer, an astrobiologist at Arizona State University in Tempe, also contends that the chance for life having existed on Mars is definitely in the cards. He is a Mars Exploration Rover science team member.

"We now have what I consider to be definitive evidence for standing bodies of water on Mars and this has opened up a serious and focused discussion of habitable environments on Mars early in the planet's history. This discovery marks a first step in implementing a strategy for Mars exopaleontology," Farmer told SPACE.com.

Farmer said the idea that Mars could have played host to Earth-launched microbes, as well as being a planet where a second genesis might have also taken place "are both contenders for an origin of Martian life and deserve serious consideration."

"I also think the idea of a 'War of the Worlds' on Mars between life forms that originated there and those that arrived from Earth is a serious possibility," Farmer said. And that prospect, he continued, raises some key questions: Who would win? Is there the possibility for a competitive co-existence between life forms that originated on a different basis?

"The good news is [that] these alternative hypotheses appear to be testable in the context of future missions. But this discussion also points, again, to the importance of planetary protection and the potential for back-contamination arising from a Martian sample return," Farmer concluded.

This article is part of SPACE.com's weekly Mystery Monday series.



#52 kevin

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Posted 03 February 2005 - 02:35 PM

Link: Link

It seems self-organizing principles may be all that is required for life after all..



Double, Double, Life’s Little Bubbles
By Sarah Webb
February 02, 2005 | Biology & Medicine


Posted Image
Courtesy of Irene Chen and Jack Szostak
In this computer model, cells with self-replicating nucleic acids (red and blue) also take in more water. They compensate for increased pressure by capturing fatty acids from the membranes of their non-replicating neighbors (white).
Jack Szostak and his colleagues at Harvard Medical School are seeking to understand the origin of life through a series of audacious experiments intended to build a basic living cell from scratch (see “What Came Before DNA?” Discover, June 2004). Using a simple experiment, they now demonstrate that one of the key steps—creating a simple growing cell by tucking self-reproducing molecules into a membrane—may be startlingly simple.

The new research rebuts the widespread belief that cells have to evolve elaborate molecular machinery to enable them to grow, one of the basic characteristics of living things. Szostak and his colleagues started with chemicals thought to have been common on early Earth: nucleic acids (the building blocks of DNA) and fatty acids. One interesting property of fatty acids is that they spontaneously form bubbles, or vesicles, that allow water molecules to pass back and forth but trap larger molecules. In the Harvard experiment, vesicles that contained relatively high concentrations of nucleic acids expanded like balloons, while nucleic acid-poor vesicles shrank. The growing vesicles cannibalized fatty acids from the shrinking ones, so they were able to keep growing without popping.

Previously, researchers have shown that some simple RNAs, the smallest about twice as long as those of the Szostak group’s simple cells, can replicate without help from other molecules. The group’s new observation is that packing a membrane with more nucleic acids makes it expand; this mechanism could provide the cells with a simple method for evolutionary competition. If some of these model cells contained nucleic acids that could replicate themselves, even inefficiently, they would have grown at the expense of competitor cells. The more effectively the nucleic-acid molecules can replicate, the more rapidly their surrounding membranes will grow. “What we showed was that you can get a Darwinian competition to emerge just from the basic physical properties of the system,” says Irene Chen, a graduate student in Szostak’s lab. “It doesn’t require biological machinery.”

#53 Mind

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Posted 06 February 2005 - 12:53 PM

Cells use a morse code-like signal to switch genes on and off, researchers have found.

The researchers, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and working at the Universities of Liverpool and Manchester and the Royal Liverpool Children’s Hospital, in collaboration with scientists at AstraZeneca and Pfizer, have studied transcription factors, the signalling molecules inside cells that activate or deactivate genes. They found that the strength of the signal is less important than the dynamic frequency pattern that is used.

Professor Michael White of the Centre for Cell Imaging at Liverpool and leader of the research group said, “The timing of the repeating signal is essential for its interpretation. It seems that cells may read the oscillations in level of transcription factors in a similar way to Morse code.”

The researchers focused on the response of a transcription factor involved in controlling the crucial processes of cell division and cell death. They found that the dynamics of the signalling molecule resemble the changes in calcium levels that encode other messages in cells. The results suggest how common signalling molecules could convey different messages through different frequencies.

Professor Douglas Kell, who sits on BBSRC Council and is a member of the research team, said, “This raises new challenges for drug designers. It appears that simply aiming to knock down signalling molecules with drugs, as many people are trying to do, may have weak or even undesirable effects as a range of signals could be cancelled out. It is going to be important in the future to decode the Morse-like messages from the molecules to make sure that only the desired effects are blocked.”


Contacts

Matt Goode , BBSRC Media Office

Tel: 01793 413299, E-mail: matt.goode@bbsrc.ac.uk

Professor Michael White, University of Liverpool

E-mail: m.white@liv.ac.uk

Professor Douglas Kell, University of Manchester

E-mail: dbk@man.ac.uk

#54 Mind

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Posted 06 February 2005 - 01:04 PM

Study finds nearly one-third of human genome regulated by RNA

Written by David Cameron.

To receive a copy of this paper, please contact newsroom@wi.mit.edu.

Full citation
Cell, Vol. 120, 15-20, January 14, 2005
"Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets"
Authors: Benjamin P. Lewis (1,2), Christopher B. Burge (1), and David P. Bartel (1,2)

(1) Department of Biology, Massachusetts Institute of Technology, Cambridge, MA
(2) Whitehead Institute for Biomedical Research, Cambridge, MA

CAMBRIDGE, Mass. (Jan. 14, 2005) — For many years, DNA and proteins have been viewed as the real movers and shakers in genomic studies, with RNA seen as little more than a messenger that shuttles information between the two. But researchers from Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology have discovered that small RNA molecules called microRNAs regulate thousands of human genes—more than one third of the genome’s protein-coding regions. In other words, a class of molecule once relegated to the sidelines may be one of the principal players in regulating cellular mechanisms.

“It’s exciting to see how many genes are regulated by microRNAs. We now know that this type of gene control is much more widespread than previously appreciated,” says Whitehead Member and MIT professor of biology David Bartel.

MicroRNAs interrupt a gene’s ability to make protein. These tiny, single-stranded pieces of RNA are newcomers to biological research. It wasn’t until 2000 that researchers even knew that microRNAs existed in humans. Now, in the January 14 edition of the journal Cell, Benjamin Lewis, a graduate student working jointly with Whitehead’s Bartel and MIT associate professor of biology Christopher Burge, provides the first evidence that microRNAs influence a large percentage of life’s functions.



#55 kevin

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Posted 28 February 2005 - 02:28 PM

Link: http://www.the-scien.../2005/2/28/32/1



THE CASE FOR RNA
A large proportion of the human genome (and those of most animals and plants) is transcribed, yet around 98% of all transcribed sequences are nonprotein-coding.4 Therefore either cells in humans and other complex organisms are replete with meaningless transcription, or these vast numbers of noncoding RNAs are also sending genetic signals into the system, presumably largely in a sequence-specific (i.e., digital) fashion.

Evidence favoring the latter case is mounting rapidly.3-6 Thousands of noncoding RNAs have been detected by cDNA cloning and by chromosome- or genome-wide transcriptome analysis using tiled microarrays, both in mammals and insects,7,8 many have been cataloged online in RNAdb [http://research.imb.uq.edu.au/rnadb]. All well-studied gene loci, including beta-globin in mammals and bithorax-abdominalA/B in Drosophila, as well as imprinted loci, produce many noncoding transcripts.6 At least some long-distance "enhancers," thought to control gene expression in cis, are transcribed in a developmentally regulated manner.9

Most of the complex genetic phenomena in higher organisms, including gene silencing, imprinting, and methylation, are connected to RNA signaling.5,6 The human genome encodes large numbers of RNA-binding proteins, and at least some "transcription factors" are known to have high affinity for nucleic acid structures involving RNA.5,6 It is likely that many of the large families of proteins and protein domains that appear to be nucleic acid- or chromatin-binding proteins, but whose actual specificity is unknown, are in fact recognizing structures containing RNA.

The recent discovery of microRNAs (miRNAs) and small interfering RNAs (siRNAs) is beginning to provide insight into this regulatory network. Derived from the introns of protein-coding transcripts and the exons and introns of some noncoding transcripts, most miRNAs are differentially expressed in different tissues and developmental stages. They act by sequence-specific recognition of other RNA targets for translational inhibition or destruction, and have been shown to control developmental events ranging from embryogenic patterning to adipocyte formation, and also to be perturbed in a range of cancers.10



Click HERE to rent this GENETICS advertising spot to support LongeCity (this will replace the google ad above).

#56 Lazarus Long

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Posted 11 June 2008 - 09:38 PM

It looks like another of our predictions is coming to pass. We might be assembling cells from scratch within the next 5 years and more probably ten, but the trend is solidly toward that result.


June 10, 2008
Scientists Close to Reconstructing First Living Cell
Researchers get genetic material to copy itself in a recreation of a simple protocell that could have existed eons ago

By Nikhil Swaminathan

******

Harvard Medical School researchers report in Nature that they have built a model of what they believe the very first living cell may have looked like, which contains a strip of genetic material surrounded by a fatty membrane. The membranes of modern cells consist of a double layer of fatty acids known as phospholipids. But in designing a membrane for their cell, scientists worked with much simpler fatty acids that they believe existed on a primeval Earth, when the first cell likely formed. The key, says study co-author Jack Szostak, a Harvard geneticist, was to develop one porous enough to let in needed nutrients (such as nucleotides, the units that make up genetic material, or DNA) but strong enough to protect the genetic material inside and keep it from slipping out after replicating.

In an attempt to duplicate an early cell, scientists put fatty acids (that were likely membrane candidates) and a strip of DNA into a test tube of water. While in there, the fatty acids formed into a ring, or membrane, around the genetic segment. The researchers then added nucleotides—units of genetic material—to the test tube to determine whether they would penetrate the membrane and copy the DNA inside it. Their findings: the nucleotides did enter the cell, latch onto and replicate the DNA over 24 hours.

What scientists now must figure out, Szostak says, is how the original and copycat DNA strands separated and this early cell divided or reproduced.

"We're trying to solve a whole series of problems, step by step," he says, "and build up to replicating an evolving system."

*****

(excerpt)

http://www.sciam.com...t...econ&sc=rss




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