deCODE Mutations Rates and Gorilla Paternity Test

Some important work in genomics just published.

Drawing on sequence data from more than 155,000 Icelanders, the deCODE researchers examined the location, rate and connection between the two key drivers of human evolution. “What we show in this paper is how tightly linked recombinations and new mutations are,” Kari Stefansson, CEO of deCODE and the senior author of the study published in Science, told FierceBiotechResearch.

Well known already:

The most important finding of the study, Stefansson said, is that mutations don’t appear to happen randomly, as scientists have long assumed. “In about a thousand bases flanking the sides of recombinations, a mutation rate is increased almost 50-fold,” Stefansson said. This suggests that crossovers do have a role in the formation of new mutations.

“The classic premise of evolution is that it is powered first by random genetic change. But we see here in great detail how this process is in fact systematically regulated—by the genome itself and by the fact that recombination and de novo mutation are linked,” Stefansson said in a statement.

Notice that these are still random mutations, because they are not entirely predetermined. They have patterns. Phenomenally important work, with implications for both medical research and population demographics.

This paper also just came out:

It’s not every day that scientists accidentally uncover a gorilla paternity scandal. But when a team of researchers led by Søren Besenbacher in Denmark went looking for genetic data on great ape families, one of their gorilla fathers “turned out to be only half as related to the child as expected,” the researchers write.

More importantly, they studied mutation rate in Gorillas, showing that it was higher rate than humans. Once again, this important implications for our understanding.

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And another very interesting paper I just discovered from 2015 on puberty and mutation rates, using this to better estimate the diivergence between humans and chimpanzees.

What does this mean? Are we talking about the mutation rate in the first cell division after meiosis? Some effect lasting for many rounds of mitosis? What is the cause, and what sort of mutations are we talking about? (I realize that these quotes aren’t yours; that’s just how it comes out.)

What evidence is there that this is any sort of regulation? And if so, regulation with what function?

Correlated with generation time, perhaps?

This is well known already by several other studies. Recombination causes mutations. Any breakage of DNA strands causes point mutations in the surrounding area, and biochemical mechanisms are well elucidated in many cases.

“Regulation” does not seem like an appropriate word.

Gorillas have a generation time that is nearly as high as ours.

Yes, and they would appear to have, on average, fewer cell divisions per generation in the male germ line. Puzzling.

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When they say “50-fold”, do they refer to a fifty-fold increase in the number of mutations seen from parent to child? I had thought that most mutations happen in gametogenesis, during genome replication. How do they even know, within a few bases, where the recombination happened?

They mean 50-fold increase near recombination break points relative to far away from recombination break points. With the mothers and fathers genomes, you can look at the child and know down to about 1000 bp where the recombination break point is.

As I’ve said, this is a well known effect of recombination. Any break in DNA (including recombination) is mutagenic.

Yes, but it’s mutagenic once, right? And right at the site of the break. If, as generally supposed, most mutations happen during genome replication during gametogenesis (specifically spermatogenesis), how could that one recombination event increase the per-generation mutation rate significantly?

I’m not sure that this is what increases the per generation rate. That is a different issue.

So what does “50-fold” mean? What background mutation rate is it referring to? The mutation rate elsewhere in the genome during/just preceding meiosis? This is highly unclear.

You can read the original paper here. That should make it more clear.

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That’s just the abstract. But it seems to refer to the per-generation mutation rate, that is, comparison between parent and child. It seems to me that this has very little effect on the overall mutation rate calculation, given the small amount of the genome this accelerated mutation rate covers. True?