by Veronique Greenwood
from QuantaMagazine Website
they noticed that although everyone had mutations,
surprisingly few people had the large numbers of mutations
that statistics would predict.
The absence of those hypothetical individuals
supports a theory about the interactions of
mutations and the evolutionary value of sex.
Sex might help natural selection
purge excessive mistakes from our
Each of us is born with about 70 new genetic errors that our parents did not have. That's much more than a slime mold, say, or a bacterium. Mutations are likely to decrease an organism's fitness, and an avalanche like this every generation could be deadly to our species.
The fact that we haven't
gone extinct suggests that over the long term, we have some way of
taking out our genetic garbage.
And a new paper (Negative Selection in Humans and Fruit Flies involves Synergistic Epistasis), recently published in Science, provides evidence that the answer may be linked to another fascinating procedure: sex.
For about three decades, one of the senior authors of that paper, Alexey Kondrashov, a biologist at University of Michigan, has explored how populations might shed such mutations.
The question poses more of a conundrum than you might think. One model of natural selection is that it acts on mutations one by one: letting this one stay, forcing that one out.
Another, though, is that the fates of mutations can be linked - an effect that population geneticists call synergistic - or narrowing - epistasis.
This might happen if having one mutation can compound the effects of another:
To Kondrashov and others, that prediction suggests an escape route from the trap of rapidly accumulating mistakes, both for humans and other multicellular organisms prone to mutations:
And in sexual organisms, because of the ways that mutations from each parent can recombine randomly onto the same chromosomes, the synergistic elimination of bad mutations can happen even faster.
professor of ecology and evolutionary biology
at the University of Michigan.
Kondrashov has investigated the implications of synergistic epistasis with theoretical studies.
Other researchers have taken the experimental route, trying to detect whether, in real life, mutations can interact with each other this way. Those tests yielded mixed results, though, perhaps because the effect would not have to be very large to keep a population from succumbing.
Now, however, Kondrashov and his co-authors have put together a statistical case, pulled from the genomes of about 2,000 people and about 300 wild fruit flies, that the effect has been quietly acting on us and other organisms all along.
Drawing on knowledge of the species' mutation rates and other factors, Mashaal Sohail, a doctoral candidate in systems biology at Harvard Medical School, and the rest of the team began by calculating what the distribution of mutations in populations of humans and flies ought to be in the absence of this purging effect.
Certain numbers of individuals in the group, for example, ought to show 100, 50 or 30 mutations. Then the scientists turned to the genomic data, looking for the distribution of mutations in real-world populations.
What they found was that significantly fewer individuals than expected had large numbers of dangerous mutations.
They are missing from the population,
This observation fits well with what should happen if mutations are not acting independently.
Shamil R. Sunyaev,
professor of biomedical informatics at Harvard Medical School
and distinguished chair in computational genomics
at Brigham and
That finding comes with some caveats.
There does not seem to be any shrinkage in the number of individuals with less-than-devastating mutations, cautioned both Kondrashov and Shamil Sunyaev, a computational geneticist at Harvard Medical School and another senior author of the paper.
The team would also like to get better data on the consequences of mutations in parts of the genome that don't make proteins.
That would let them run their statistical tests again with more confidence that the interactions are occurring more broadly.
Still, the evidence is provocative, and the idea elegant.
Of the new work, he said,
Perhaps the most interesting corollary of this finding, however, is that it might help explain the persistence of sex.
Among population geneticists, sexual reproduction is notoriously difficult to justify as an evolutionary strategy. As a sexual organism, even if everything goes well - if you manage to find a mate who accepts you, if you manage to conceive - you will still be passing on only half of your genes.
An asexually reproducing organism, having daughters by making perfect copies of itself, gets double the benefit, none of the hassle.
Yet clearly, sex continues.
The redeeming feature of sex, when it comes to evolution, seems to be that it shuffles the parents' genes together in endlessly new combinations.
Unless you have an identical twin, none of your siblings are just like you. And each of your sperm or egg cells carries a mish-mash of your own genes, so none of your children will get the same thing.
Sex leads to greater variety for natural selection to work with, a wider palate of quirks, abilities, shapes and sizes that might be fitted to the situation at hand.
The benefits of this arrangement may exceed the costs, though, when there is some efficient way to get rid of the real genetic disasters. And that's where this new work comes in.
Dangerous mutations can be wiped out from the population en masse only if they happen to get shuffled together, thanks to sex, into the same individual.
That unlucky "individual" loaded with bad mutations could be a sperm cell that's not fit enough to ever reach an egg, or an organism that is not healthy enough to ever reproduce.
Either way, that combination of mutations would drop out of the population, never to be passed on.
At one stroke, then, a large mass of worrisome problems - brought together by sex, then doomed by their associations with one another - would be culled from the gene pool.
Nearly 30 years ago, Kondrashov, then a scientist in the Soviet Union, wrote a paper for Nature (Deleterious Mutations and the Evolution of Sexual Reproduction) that pointed out this process, now called the deterministic mutation hypothesis, could help to justify sex.
In an asexual population, because the members are genetically identical, natural selection can't purge bad mutations rapidly without killing everyone.
Speaking from his summer research base near Moscow, Kondrashov said he hopes to see more experimental verification of the interactions between mutations.
Next he plans to raise a carefully controlled population of fruit flies in which the genetic variation among individuals is known from the beginning, and then to run selection experiments to see in more precise detail exactly how it changes over time.
Furthermore, the statistical test the group uses should be applicable to any population where researchers have some basic information to plug in, Arjan de Visser noted.
It would be relatively straightforward for other scientists to apply it and see if they can uncover similar interactions in other human or animal populations.
It is easy to assume that, in an era with modern medicine and agriculture, we humans have somehow escaped the grasp of natural selection.
But this glimpse into the mutational landscape of the human genome shows selection may still be acting on us without our noticing it, even as our numbers boom.
These absences in the population, these empty places at the high end of the mutational distribution - these may be selection's fingerprints on our DNA...