different mutation rates in different human populations

well this seems important! via race/history/evolution notes, an abstract from the society for molecular biology and evolution 2014 conference (in puerto rico! – teh scientists are always good to themselves whenever they can be (~_^) ):

Evidence for different mutation rates across human populations
Ron Do, David Reich
Department of Genetics, Harvard Medical School, Boston, USA

Although mutation rates (per base pair) have clearly changed across primate evolution, many analyses continue to assume that all present-day human populations have the same mutation rates. Recently, William Amos analyzed 1000 Genomes Project and Complete Genomics sequences and found evidence of significantly higher divergence rates on African than on non-African lineages since separation (W. Amos, PLoS One 4, e63048). The detected pattern was strongest in genomic regions of high polymorphism rate, a pattern that the author hypothesized was due to ‘heterozygote instability’, whereby gene conversion events surrounding heterozygous sites increase the mutation rate. To further test this observation, we measured the relative accumulation of mutations in lineages drawn from two different populations, using 25 deep genome sequences generated according to the same experimental protocol using the Illumina technology. We carried out pairwise comparisons of five sub-Saharan African (Dinka, Mandenka, Mbuti, San, Yoruba) and eight Non-African populations (Australian, Dai, French, Han, Karitiana, Mixe, Papuan, Sardinian) on all divergent sites. We observed statistically significant differences in the relative accumulation of mutations for many pairs of African and Non-African populations. Among the strongest differences is significantly more lineage-specific mutations in Mbuti than in Han Chinese (R=1.044, standard error (SE) =0.0015). On average, we observed about 1% more mutations on African lineages compared to Non-African lineages. We also observed some significant differences across non-African populations, with the Han Chinese who have experienced extreme expansions in population size associated with agriculture having more mutations than the Karitiana, a hunter-gatherer population from Amazonia who did not experience such expansions (R=1.015, SE=0.0014). The results are consistent across both European and African segments of the human reference sequence, so are not an artifact of reference sequence bias. Taken together, these results support the view that per-base pair mutation rates may be dynamically and substantially changing across humans.

cool!

wrt to greater number of mutations in african lineages: polygamy (and, therefore, older fathers)? life in the tropics?

(note: comments do not require an email. old san juan. (^_^) )

11 Comments

  1. wrt to greater number of mutations in african lineages: polygamy (and, therefore, older fathers)? life in the tropics?

    Oceanian and Antipodean hunter gatherers and horticulturalists, like the Papuans and Negritos, who have subsistence and thereby similar polygamy patterns with radically different overall genetic diversity and structure would be an interesting check on this idea.

    Africans have a high genetic diversity, so I would wonder whether high buildup of mutations might be a matter of affordance, affording to take more mutational load. So in theory, in Africans, a locus can take a deleterious variant, because an adaptive variant at another locus that isn’t yet swept to fixation will increase in frequency to take up the slack. In the Papuans, all the “good stuff” by contrast would basically tend more to already be at fixture. I’m far from being a geneticist who understands whether that’s plausible at all.

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  2. From a Greg Cochran West Hunter post of Aug. 24. 2012 http://westhunt.wordpress.com/2012/08/24/men-and-macaques/

    “So, assuming that African populations have more neutral variation than non-African populations (which is well-established), what do we expect to see when we compare the levels of probably-damaging mutations in those two populations? If the Africans and non-Africans had experienced essentially similar mutation rates and selective pressures over the past few thousand years, we would expect to see the same levels of probably-damaging mutations. Bottlenecks that happened at the last glacial maximum or in the expansion out of Africa are irrelevant – too long ago to matter.

    “But we don’t. The amount of rare synonymous stuff is about 22% higher in Africans. The amount of rare nonsynonymous stuff (usually at least slightly deleterious) is 20.6% higher. The number of rare variants predicted to be more deleterious is ~21.6% higher. The amount of stuff predicted to be even more deleterious is ~27% higher. The number of harmful looking loss-of-function mutations (yet more deleterious) is 25% higher.

    “It looks as if the excess grows as the severity of the mutations increases. There is a scenario in which this is possible: the mutation rate in Africa has increased recently. Not yesterday, but, say, over the past few thousand years.”

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  3. “Africans have a high genetic diversity”: I understand that that excess genetic diversity is almost all attributable to the bushmen/hottentots.

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  4. A friend of mine once said that sub-Saharan Africans simply have not made selections. This would explain the excess of genetic diversity and probably excessive deleterious mutations. Selections clean these types of mutations.
    It also seems that most of the mutations within the sub-Saharan Africans are by natural selection. This would explain the disproportionate amount of sprinters Olympic champions, between them and especially among certain ethnic groups.
    The timing of a selection for specific traits in many parts of Africa, is the same duration of a democracy on the continent. Unstable societies can produce constant changes in demographic planning long-term and this includes model selection.

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  5. @matt – “So in theory, in Africans, a locus can take a deleterious variant, because an adaptive variant at another locus that isn’t yet swept to fixation will increase in frequency to take up the slack.”

    that’s an interesting idea.

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  6. @dearieme – “I understand that that excess genetic diversity is almost all attributable to the bushmen/hottentots.”

    hmmmm. the strongest divergence these researchers found in terms of mutations was between the mbuti (pygmies) and the han chinese. maybe pygmies also have a lot of genetic diversity?

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  7. @erica – “There is a scenario in which this is possible: the mutation rate in Africa has increased recently. Not yesterday, but, say, over the past few thousand years.

    somebody should get cochran a t-shirt that says: “i told ya so!” (~_^)

    thanks!

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  8. “somebody should get cochran a t-shirt that says:’i told ya so!’ ” (~_^)

    Not a bad idea; I’m sure he’d love it! :)

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  9. I’m not convinced: the possible effect I was discussing, an increased mutation rate stemming from older fathers, applies to polygamous farmers, not Pygmies. But since the highest rate is seen in Pygmies, probably I was wrong.

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  10. Sub-saharan Africans have reduced hot-spot utilization for recombination due to differences in the PRDM9 gene. Why is it not equally plausible that there are differences in de-novo mutation rates due to genetic diversity on a gene responsible for replication fidelity. This seems to be a more likely explanation than trying to explain the differences using culture or weather.

    Reply

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