Modern humans dispersed out of Africa and expanded onto multiple continents around 50,000 years ago. Researchers studying the genetic impact of our species’ expansion reveal that the distance from sub-Saharan Africa can help predict the number of deleterious mutations in a genome. The findings are published in Proceedings of the National Academy of Sciences this week.
Each human genome contains hundreds of potentially harmful mutations, and many of these would be pathogenic if expressed in a homozygous state – that is, if we had two copies of that gene variant (called an allele), one from mom and another from dad. However, it remains unclear if the number of deleterious mutations varies significantly among populations. Based on population genetics theory, groups undergoing a series of founder effects (rather than a single bottleneck) during range expansions likely show an increase in what’s called mutational load – the genetic burden of deleterious mutations.
To test this, Stony Brook’s Brenna Henn and colleagues analyzed whole-genome sequence data of more than 50 people from seven geographically divergent groups: Namibian San, Mbuti Pygmy (from the Democratic Republic of Congo), Algerian Mozabite, Pakistani Pathan, Cambodian, Siberian Yakut, and Mexican Mayan populations.
"There is a lot variation among individuals within a population, but there is a general trend when you look at the population averages," Henn explains to IFLScience. "The effect is modest because there is really only a difference of a couple hundred deleterious mutations carried between different individuals at different ends of the spectrum." And that’s a small number given the total number of mutations.
The trend across the seven populations, on the other hand, is significant and correlates with increasing distance from sub-Saharan Africa. At the population level, deleterious mutations were more common in non-African populations than in African populations. This becomes especially clear with recessive genes, and many disease-causing mutations are thought to be recessive. "Populations who left Africa 50,000 years ago have higher homozygosity," Henn adds, "so if they carry a deleterious recessive mutation, it is more likely to be penetrant."
Selection against strongly deleterious mutations was greater in African populations, and during our early expansion, many (moderately) deleterious mutations evolved as if they were neutral. Some turned out to be beneficial in new environments.
1