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Study Suggests Genome Instability Hotspots
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."
"...evolved to the point where they work well with evolution"
ya think?
If you can read this, I forgot to post anonymously.
I guess Cold Spring Harbor (authors) weren't able to withstand James Watson's instability. They couldn't tolerate most of his comments.
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.
It's been known for quite a while that certain sections of the genome mutate faster than others. Areas where the genes are less likely to mutate are typically referred to as 'conserved' regions, and most genome browsers will even indicate which regions they are. The UCSC genome browser is great for checking things like this (http://genome.ucsc.edu/). With that browser, you can look up genes and compare them to the coding sequences in other animals.
For very highly conserved genes such as the homeobox sequences, the degree of conservation is enormous. Nearly everything has the homeobox -or 'hox' sequence, and the sequence itself hasn't changed significantly (in comparison to most other genes). tRNA sequences as well don't change significantly; neither do ribosomal genes. Some stuff you simply can't change without experiencing lethal (or at least highly detrimental) results.
Other regions such as non-coding regions, and introns to a lesser extent, can be mutated significantly without any change to the phenotype of the organism. In fact, this is what a lot of DNA fingerprinting is based on - big variations in sequence lengths and other polymorphisms between individuals. These variations don't occur frequently enough within coding sequences to be of any use in identification. Rather, they check the non-coding areas and other mutational hotspots for differences. Conversely, changes in the protein-coding regions can be used to determine the relatedness between species (say, human and chimp differences, or rat and mouse) on a much longer scale.
Now, having said that, there are always exceptions. Some organisms have entirely novel mutation patterns. The influenza virus (admittedly, not an organism in the traditional sense) mutates almost exclusively in the coding areas of its envelope proteins. Even stranger, only 1 strain of the virus seems to survive every year to propagate the next. (See the 2001 article by Bull and Wichman entitled "Applied Evolution" in the journal 'Annual Review of Ecological Systems".)
Basically, what I'm saying is that the fact that some parts of the genome mutate faster than others is something we already know. This isn't necessarily news. The only way I can think that this would be significant is that lab mice are generally thought to be basically genetically identical. They're normally inbred for about 20 generations (most don't survive past 7) to ensure the homozygosity of the mice. Inbred mice like this are valuable because the way they react is consistent and reproducible (traits that are mainstays of science). If they're mutating faster than we expected, it may have an affect on the reliability of the studies done with these mice.
"Operating systems suck: you're better off using only the BIOS" --trainsaw.com
you must be the one that keeps posting those fisting stories....
no.
That kinda study would be nice, though.
Perhaps because it's 1AM? Check back in the morning.
Maybe the religious types have earlier bedtimes?
{sarcasm}
Oh! Maybe they blame the scientists for screwing up the mice for that many generations (too many weird chemicals in the lab). After all, scientists aren't examining nature (in which animals don't evolve) in this study. They're examining mice that they trained to evolve! Scientists are making up the so-called evidence right? Yeah, they make freaky mice in a laboratory, but that doesn't mean that everything else evolves does it?
{/sarcasm}
"Operating systems suck: you're better off using only the BIOS" --trainsaw.com
It's 3pm in the afternoon where I am Taipei, but there's probably almost 0 creationists around here. I guess creationists all live on the other side of the flat earth.
Australian running a company that does C# / C++ / Java / SQL / Python / Mathematica
"Ars Technica goes on to recount suggestions that genomes evolved to the point where they work well with evolution."
I wouldn't put it past those Godless bohemian radicals to deny Devine Intervention in the creation of species.
Pish and Tush, I say. Pish and Tush.
There is a reason religion is expected to mix badly with science here on slashdot. Namely because one requires evidence without faith and the other requires faith without evidence. Religious fundamentalism requires that a person believe unquestionably in a text. Some people take it way too far as to attack anything that opposes their religious views although this is generally a minority view. I will say this though, anyone who blindly opposes scientific principles in favor of their pre-conceived beliefs on the world has my complete contempt.
Sigs are too short to say anything truly profound so read the above post instead.
The irony is that while there is no pro-religion flamebait, you still had your anti-religion flamebait ready to go. Maybe we shouldn't drag religion needlessly into discussions?
"16MB (fuck off, MiB fascists)" - The Mighty Buzzard
Perhaps the discussion is on a level higher than it sounds, but isn't this obvious? It's no mystery that replacing your eyeballs with extra anuses is going to have a much bigger impact on your survivability than, say, having green skin. Natural selection follows suit, and certain parts of the genome should simply not be fucked with.
Did anyone read that as "Study Suggests Gnome Instability Hotspots"? LOL. Must be the coffee at 2AM, and the endless lines of code I'm staring at.
So... ...viable organisms tend to have variations in bits of their genome that don't determine whether they'll be viable or not... ...obvious as it sounds.
OK, forgive me if I'm missing something & this isn't as...
Maybe the organisms with changes in parts of their genome that are not tollerant to change are DEAD....
I would be more surprised if a similar study of stillborn and aborted rats found the same tendency.
thx e
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.
A polar bear is a cartesian bear after a coordinate transform.
What you call faith, I call superstition. I see faith as something a little more defensible and and overlapping with "trust". Rules of evidence come into play, but there is still a bit of a leap involved. Human relationships present us with analogies for a relationship with the divine. On that note, I'll end my comment, because going further would be off-topic.
Yes, it seems fairly obvious that a creature might have adapted its evolutionary mutations to mutate things aren't quite proven yet, and to not mess with things that are "backbones" (literally or figuratively) of the design.
The question for me is... WHERE is that information stored? In another part of the DNA? If so, it becomes metaprogramming. Somewhere else? If so, there's a new type of DNA (unless RNA etc. qualify as that; I'm no geneticist, admittedly).
Thank you for that post. Too many discussions about interesting topics are destroyed because we get people in here trying to preempt a discussion that probably wouldn't occur.
Out of modpoints but really liked a post? 1BDkF6TtmmeZ3yqXbz9yhdYVqRYnwFoXDj
Everyone knows Tinker Town is the #1 gnome hotspot!
Our intelligent designer has never created an animal that we couldn't improve by strapping a bomb to it.
perhaps they should try KeDE?
I'll game: "God does not play dice with genes, only with your money."
Table-ized A.I.
The claims seem rather circular under the light of evolution. Some places tolerate more mutations and they change more. Well duh, that's evolution for you. If it had an intolerable mutation it would die off so the majority of mutations are going to happen in the most tolerated places like junk DNA and the ultra-conserved sections should be exceedingly intolerable for mutations (although a study a couple months had an odd problem with that).
This is about as amazing as getting a group of people who roll dice for a while and nobody rolls two 1s in a row when you shoot anybody who rolls one 1.
It is no longer uncommon to be uncommon.
And here I was... thinking this story would mark locations on a world map deemed "genome instable hotspots", such as the immediate area around Tchernobyl and the state of Texas.
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.
Essentia non sunt multiplicanda praeter necessitatem.
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
Essentia non sunt multiplicanda praeter necessitatem.