Hi apoptosos, you are right to prompt me again. I'm trying to find the answers I don't have them!
I've been doing a little googling trying to find a link between sloppy "dna repair" and "gene creation". Of course this is all well over my head here but I'm not letting that stop me
http://www.nature.co...EB0B0F1249DFBC1"Human subtelomeres are polymorphic patchworks of interchromosomal segmental duplications at the ends of chromosomes. Here we provide evidence that these patchworks arose recently through repeated translocations between chromosome ends. We assess the relative contribution of the principal mechanisms of ectopic DNA repair to the formation of subtelomeric duplications and find that
non-homologous end-joining predominates. Once subtelomeric duplications arise, they are prone to homology-based sequence transfers as shown by the incongruent phylogenetic relationships of neighbouring sections.
Interchromosomal recombination of subtelomeres is a potent force for recent change. Cytogenetic and sequence analyses reveal that pieces of the
subtelomeric patchwork have changed location and copy number with unprecedented frequency during primate evolution. Half of the known subtelomeric sequence has formed recently, through human-specific sequence transfers and duplications. Subtelomeric dynamics result in a gene duplication rate significantly higher than the genome average and could have
both advantageous and pathological consequences in human biology. More generally, our analyses suggest an evolutionary cycle between segmental polymorphisms and genome rearrangements."
Now lets have a look at wikipedia for NHEJ:
http://en.wikipedia....ous_end_joining"Nevertheless, NHEJ is often somewhat misleadingly referred to as an "error-prone" repair mechanism. This is likely because NHEJ can lead to translocations when organisms are subjected to large doses of radiation that cause many breaks per cell. Additionally, the NHEJ pathway is responsible for fusing the ends of chromosomes that have undergone telomere failure.[5] These translocations may result in incorrect gene regulation, and (ultimately) cancer"
That doesn't seem to provide any evidence for my hypothesis (if I manage to cleanly state one) at all.
Lets keep reading:
"Unlike typical cellular NHEJ, in which accurate repair is the most favorable outcome, error-prone repair in V(D)J recombination is beneficial in that it maximizes diversity in the coding sequence of these genes. This role of NHEJ has also contributed to its reputation as an error-prone DNA repair pathway. Patients with mutations in RAG-1, RAG-2, and Artemis are unable to produce functional B cells and T cells and suffer from severe combined immunodeficiency (SCID)."
So what is this V(D)J recombination?
http://en.wikipedia....J_recombinationNow i'm doing a little googling for "error prone" "dna repair"
http://www.ncbi.nlm....t_uids=16678112"p53 and p21 regulate error-prone DNA repair to yield a lower mutation load.
Avkin S, Sevilya Z, Toube L, Geacintov N, Chaney SG, Oren M, Livneh Z.
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Regulation of mutation rates is critical for maintaining genome stability and controlling cancer risk. A special challenge to this regulation is the presence of multiple mutagenic DNA polymerases in mammals. These polymerases function in translesion DNA synthesis (TLS), an error-prone DNA repair process that involves DNA synthesis across DNA lesions. We found that in mammalian cells TLS is controlled by the tumor suppressor p53, and by the cell cycle inhibitor p21 via its PCNA-interacting domain, to maintain a low mutagenic load at the price of reduced repair efficiency. This regulation may be mediated by binding of p21 to PCNA and via DNA damage-induced ubiquitination of PCNA, which is stimulated by p53 and p21. Loss of this regulation by inactivation of p53 or p21 causes an out of control lesion-bypass activity, which increases the mutational load and might therefore play a role in pathogenic processes caused by genetic instability."
Lets look for a few more articles on TLS:
http://www.genesdev....full/16/15/1872"Cellular DNA is continually damaged by a plethora of extrinsic and intrinsic sources, including UV light from the sun and reactive oxygen species resulting from aerobic respiration. Although cells possess a variety of repair processes to remove DNA lesions, lesions that escape repair can block the replicational machinery, and there has been little understanding of the mechanisms by which eukaryotic cells overcome such blocks and promote the continuity of the newly replicated DNA strand. The past three years, however, have witnessed phenomenal progress in this area of research, and here we highlight the important findings and major conclusions that have emerged regarding translesion DNA synthesis (TLS) in eukaryotes."
This is an interesting one on DNA damage bypass
http://asajj.roswell...air/bypass.html"There are two reasons why it is important for the cell to be able to move replication forks past unrepaired damage. First, long-term blockage of replication forks leads to cell death. Second, replication of damaged DNA provides a sister chromatid that can be used as template for subsequent repair by homologous recombination."
Hey does anyone know anything more about the "inducible sos hypothesis"?
http://cat.inist.fr/...cpsidt=16815158"Evelyn Witkin hypothesized in 1967 that bacterial cell division is controlled by a repressor which, like the lambda repressor, is inactivated by a complex process that starts with the presence of replication-blocking lesions in the DNA. She further suggested that this might not be the only cellular function to show induction by DNA damage. Three years later, Miroslav Radman, in a privately circulated note, proposed that one such function might be an inaccurate (mutation-prone) DNA polymerase under the control of the recA and lexA genes. Thus was born the SOS hypothesis"
Also:
Research Article
DNA lesions, inducible DNA repair, and cell division: three key factors in mutagenesis and carcinogenesis.
http://www.pubmedcen...i?artid=1519422I think the jury is still out on this and I need to do a lot more reading.
I also confess ideological bias against your hypothesis. It's bad enough that death of individuals is commonly excused as a necessity for natural evolution, as if blind evolution for evolution's sake was some kind of higher cause than individual lives. It would be another talking point for excuse makers if the mechanism of natural evolution itself, mutation, was a major contributor to the aging and death of individuals. I do not believe it is.
Good point but since when is evolution a higher cause? Maybe the whole point of evolution is that it eventually results in an individual that becomes conscious of itself and says "damn this thing is killing me lets turn it off now"
Edited by caston, 16 July 2007 - 05:39 AM.
