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Biotech Science

Study Suggests Genome Instability Hotspots 72

Posted by Zonk
from the perfect-place-to-splice dept.
Dr. Eggman writes "Ars Technica reports on a new study that suggests not only that certain areas of the mouse genome undergo more changes, but that changes to those areas are more tolerable by the organism than changes in other areas. Recently published in Nature Genetics, the study examined the certain copy number variations of the C57Bl/6 strain in mice that have been diverging for less than 1,000 generations. The results were a surprising number of variations. While the study does not address it, Ars Technica goes on to recount suggestions that genomes evolved to the point where they work well with evolution."
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Study Suggests Genome Instability Hotspots

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  • The Next Step (Score:5, Interesting)

    by Raindance (680694) * <johnsonmx.gmail@com> on Monday November 05, 2007 @01:43AM (#21238305) Homepage Journal
    not only that certain areas of the mouse genome undergo more changes, but that changes to those areas are more tolerable by the organism than changes in other areas.

    I think a fascinating next step would be to see if, statistically speaking, viruses and transposons were channeled into jumping into these "safer to change" hotspots rather than other, more fragile areas of the genome.

    It would seem to make some sense, given all the potential for genomic havok inherent in viruses and transposons' tendency toward hopping into the middle of genes.
  • by Moraelin (679338) on Monday November 05, 2007 @06:55AM (#21239467) Journal
    That's a bit putting the carriage before the horse, IMHO.

    What this really says is that the genome became, more or less, fault-tolerant. The ability to evolve really came out of that.

    For starters, there is no part of the genome or ribosomes or whatever that actually produces mutations. On the contrary, most of the complexity in your cells is to prevent mutations, to the best of possibilities. It's the only way to have a coherent organism made of gazillions of cells. You don't want a cell in your palm to think it's supposed to grow into a nose, for example. And you really don't want cells to just start divided uncontrolled.

    And you or the mouse have layers upon layers of defenses against that. The very reason why we're DNA based instead of RNA is to allow repairing single-strand mutations. But it goes on from there.

    The very fact that you age is, pretty much, a defense against cancer: cells have a maximum division number counter, based on what tumor size still likely wouldn't kill you. (Hence also why larger species tend to live longer: they get a bigger limit there.) When more and more cells have reached that limit, then more and more damage can't be repaired, and you discover the fun of old age. And then you die.

    Etc.

    At any rate, the major thing is: there is no part in the genome that says you should evolve. Read: mutate. It actually tries to prevent mutations, hence evolution.

    But mutations happen anyway, and some will happen in the sperm or eggs, or the first stages of embryo formation. You can't 100% prevent those. They _will_ happen. And the choices from there are basically two: either the result can still live with that mutation, or it dies.

    Hence what they discovered here: natural selection favours the kind of genome that can tolerate mutations when they happen anyway. A species where the slightest change results in death will be at a disadvantage, compared to a species where more individuals survive even with mutations.

    Sure, in the long term that also means being to evolve and cope with environment changes. No doubt. But I think there's a far stronger short-term pressure to achieve the same result. And most likely that's really what we're seeing there.
  • by Lurker2288 (995635) on Monday November 05, 2007 @09:57AM (#21240575)
    "Hence what they discovered here: natural selection favours the kind of genome that can tolerate mutations when they happen anyway."

    That's true more or less by definition, but I think you're overlooking something simple. A more complex organism has more opportunities for nonfatal mutations. That is, Mycoplasm genitalium, probably the simplest known bacterium, is extremely vulnerable to deleterious mutations. If it loses a gene that codes for a vital self-component, odds are it hasn't got a backup process for that component--it's dead. Whereas a more metabolically complex bacterium may have multiple pathways that produce necessary components. So it's not surprising that when we look at complex genomes, we see the capability to withstand mutation.

    So greater complexity (more genome) means more opportunity for mutation, but also more redundacy and failure tolerance. So it's no surprise that
  • by protobion (870000) on Monday November 05, 2007 @12:03PM (#21241883) Homepage
    Unfortunately, ars technica and by consequence Slashdot, have completely mis-interpreted the original paper, at least regarding the headline used. As many people have stated, there is no wonder in finding that there are genome instability hot-spots. This has been known for years. What was not obvious , is the existence of hot-spots leading to a specific kind of mutation - i.e , copy number variation (CNV). Even though CNVs are mutations in the classical sense, modern molecular biology reserves the term 'mutation' for single nucleotide or codon changes. Drastic changes at the genomic, chromosomal or transcript level are generally called by their specific names such as deletion, truncation, transposition, duplication etc. What this study seems to suggest is that certain regions of the genome (irrespective, it seems, if these regions are genes or have a known biological function) seem to have a fluctuating copy number in the genome, with the rate of fluctuation much higher than expected in a random process - suggesting the existence of a mechanism that allows for this fluctuation to occur. It implies, that evolution has caused these particular regions to become uncoupled from potential lethality or drastic abnormality that arises in organisms , when similar variations occur on other regions (for example: variation in X-chromosome number leads to Turner or Klinefelter's syndrome). The interesting question that I see, is if there is a mechanism that allows this "tolerance" to exist to variations in these particular regions, and if there is such a mechanism, can it be tailored to allow changes in other regions...leading to the possibility of creating strains of organisms specially suited for particular scientific experiments-with multiple copies of a gene etc. - animals that currently are simply impossible to create because these changes are lethal. A far shot would be therapeutics. There are certain diseases that arise simply because of a cells inability to tolerate certain changes in the genome, irrespective of whether those changes are the cause of the lethality. In other words, the cells defense system itself is the cause of the disease rather than the genetic change. This might be the case in several autoimmune diseases or developmental diseases where upon sensing a genetic change, cells undergo apoptosis - irrespective of whether the genetic change is detrimental during the natural life of the cell. So, if one reads the Nature article, there is really some news there.
  • by wizardforce (1005805) on Monday November 05, 2007 @12:29PM (#21242269) Journal

    For starters, there is no part of the genome or ribosomes or whatever that actually produces mutations. On the contrary, most of the complexity in your cells is to prevent mutations, to the best of possibilities.
    I used to think the same way about it but the more I looked into it the more I realized that there is a way for species to regulate their evolution in a way. Genetic repair mechanisms to be exact. They have evolved to have some level of accuracy; this is different depending on what species you are talking about. Over time, species would evolve genetic repair mechanisms that best suited their survival. A perfect repair mechanism isn't necessarily in a species' best interest. If your genetic code doesn't mutate, your species isn't going anywhere evolutionarily because it can not change- it can't adapt as well as a species whose genetic code could mutate more frequently. Too many mutations kill organisms so over time you would expect there to be an equilibrium between a very efficient genetic repair mechanism and one that allowed for genetic change. That's including a genome where you can fiddle with what is there and be ok- there's nothing preventing that either.

    The very fact that you age is, pretty much, a defense against cancer: cells have a maximum division number counter, based on what tumor size still likely wouldn't kill you. (Hence also why larger species tend to live longer: they get a bigger limit there.) When more and more cells have reached that limit, then more and more damage can't be repaired, and you discover the fun of old age. And then you die
    The shortening of telemeres with age does indeed protect against cancer although the link between the length of a telemere is a dubious test of longevity. some small rodents for example, lengthen their telemeres because the gene that produces telemerase doesn't switch off in early development like a lot of other species. They don't live that long, not because of the length of their telemeres, but because of other factors. Consider this: suppose there were a vastly more efficient genetic repair enzyme that caused bacteria to be far less likely to mutate. Would this enzyme give an overall advantage [preventing deleterious mutations] over the current genetic repair enzymes [good but not perfect] in the case of antibiotics? In that case, a lack of genetic change is a disadvantage.

Premature optimization is the root of all evil. -- D.E. Knuth

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