The survival of the human species in the face of a high number of incoming genetic mutations has remained an important problem in evolutionary biology. A newborn human is estimated to receive about 70 new mutations that the parents did not have. While these provide a source of novelty for the species, a large fraction of them can also be damaging, or likely to interfere with the biological function that a gene has for the organism. So how do we not mutate into oblivion?

A study published today in Science by Shamil Sunyaev and colleagues reports that as a species, humans get around this mutation problem thanks to certain interdependencies within the genome. Basically, if a new mutation occurs in a genome that already contains many damaging mutations, it has a stronger effect than if it occurred in a genome with just a few other damaging mutations. Thus, when a genome carries beyond a certain number of damaging mutations, it is significantly less likely to contribute progeny to the next generation.

Researchers including lead author Mashaal Sohail, PhD candidate in Systems Biology at HMS, studied population samples from Europe, Asia and Africa and found a significant depletion of individuals carrying a large number of highly damaging mutations overall. Their results suggests that natural selection against highly damaging genetic mutations is ongoing in humans, and that it is aided by synergistic interactions between different parts of the human genome, a form of epistasis. As selection due to pre-reproductive mortality is deeply relaxed in industrialized humans, it is likely that the observed signal comes from selection due to differential fertility, or pre-natal selection (only ~30% of human conceptions result in live births). This observation is general and is not limited to our own species. The same effect was independently observed in fruit flies.

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