Human Mutation Rates Steady Across GroupsExcept in the Amish – The Scientist

The rate of new mutations in the human genome appear to be consistent across diverse populations, except onethe Old Order Amish of Lancaster, Pennsylvania. This group has a lower rate of developing new mutations, according to a study published January 21 in PNAS.The lower mutation rate does not appear to have a genetic component, pointing to a possible role for environmental factors in modifying how fast human genomes accrue new mutations.

It really looks like environmental differences might actually [have] the most significant effect on the number of mutations that you pass on to your offspring, rather than . . . there being some sort of gene causing mutations, says Aylwyn Scally, a geneticist at the University of Cambridge who was not involved in the work. In a larger study than this one, researchers might be better able to detect a genetic contribution if there is one, he says. But still its surprising that it hasnt jumped out, and instead theres this curious effect thats bolstered by their finding about the Amish. Maybe different environments are actually the biggest factor.

Mutation rates are a source of genetic variation within populations. Knowing more about these rates in humans can help researchers better understand disease and evolution. Before this study, mutation rates had really only been looked at in Europeans, and so we wanted to be able to look in a much broader, diverse population, evolutionary geneticist Timothy OConnor of the University of Maryland, a coauthor on the new paper, tells The Scientist.

To this end, he and his colleagues leveraged a dataset of whole genomes from more than 1,400 parent-child trios from the National Heart, Lung, and Blood Institutes TOPMed (Trans-Omics for Precision Medicine) program. The team found that the rate of de novo mutations was similar across populations of African, Latino, and European ancestry. That finding was intriguing because previous work had suggested that populations with high levels of genetic diversity, such as those of African descent, would have higher mutation rates.

Even more unexpected was the mutation rate detected in the 59 Amish families in the cohort. These Amish families are of European descent but have been genetically isolated from other populations since the 1700s and all descended from about 700 individual founders. They had a seven-percent-lower mutation rate compared with the other populations.

We were pretty surprised, says OConnor. Initially the team thought the lower mutation rate had to be an artifact of the sequencing or analysis. We did basically everything we could to try and figure out what kind of artifact would be causing it, and we couldnt find one.

The research team next tried to pinpoint what caused the Amish to have a lower incidence of new mutations. OConnor and his colleagues determined that the lower mutation rates were not heritable, which led the team to speculate that environmental factorssuch as the typical Amish diet and limits on technologymay contribute.

The findings are novel in that the reduced mutation rate hasnt been previously shown with so much sequencing data, says Heather Wheeler, a geneticist at Loyola University Chicago who was not involved in the study. The caveat is that it was still just in one group, and there were only 59 families in the Amish population, she notes. If this is a real effectthe clean-living hypothesis they proposewe definitely want to see it validated in other populations that have similar environments to the Amish.

M.D. Kessler et al., De novo mutations across 1,465 diverse genomes reveal mutational insights and reductions in the Amish founder population,PNAS,doi:10.1073/pnas.1902766117, 2020.

Abby Olena is a freelance journalist based in Alabama. Find her on Twitter@abbyolena.

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Human Mutation Rates Steady Across GroupsExcept in the Amish - The Scientist