August 27, 2013

Population growth and deleterious mutations

Genetics doi: 10.1534/genetics.113.153973

Population Growth Inflates the Per-Individual Number of Deleterious Mutations and Reduces Their Mean Effect

Elodie Gazave et al.

This study addresses the question of how purifying selection operates during recent rapid population growth such as has been experienced by human populations. This is not a straightforward problem because the human population is not at equilibrium: population genetics predicts that, on the one hand, the efficacy of natural selection increases as population size increases, eliminating ever more weakly deleterious variants; on the other hand, a larger number of deleterious mutations will be introduced into the population and will be more likely to increase in their number of copies as the population grows. To understand how patterns of human genetic variation have been shaped by the interaction of natural selection and population growth, we examined the trajectories of mutations with varying selection coefficients using computer simulations. We observed that while population growth dramatically increases the number of deleterious segregating sites in the population, it only mildly increases the number carried by each individual. Our simulations also show an increased efficacy of natural selection, reflected in a higher fraction of deleterious mutations eliminated at each generation, and a more efficient elimination of the most deleterious ones. As a consequence, while each individual carries a larger number of deleterious alleles than expected in the absence of growth, the average selection coefficient of each segregating allele is less deleterious. Combined, our results suggest that the genetic risk of complex diseases might be distributed across a larger number of more weakly deleterious rare variants.

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3 comments:

Grognard said...

Pretty interesting, we don't hear enough about puridying selection

terryt said...

"while population growth dramatically increases the number of deleterious segregating sites in the population, it only mildly increases the number carried by each individual".

But isn't that simply the result of outbreeding? The greater the population the more thinly strung out any particular mutation will be.

" Our simulations also show an increased efficacy of natural selection, reflected in a higher fraction of deleterious mutations eliminated at each generation, and a more efficient elimination of the most deleterious ones".

Presumably individuals carrying the most deleterious mutations, even as a recessive, will leave fewer descendants. As a result the mutation would be less likely to survive as against less deleterious mutations. In the case of inbreeding a population would have fewer genes available to work with and so more deleterious genes may survive in such a population as recessives.

Grognard said...

Yes and no. Obviously they are talkinf about population size so yes inbreeding is part of the issue but they are really talking about "acceleration".

The idea is in small population you have much more drift, going in a sometimes very bad direction in the entire population. Which I have pointed out before as a way y-DNA and mtDNA can easily trickle out of a small population. That's what we expect to happen for introgressions into a larger group.

But for a larger population you have many more actually bad genes running around as well because you get many more mutations.

This is called acceleration. Drift is eliminated and only selection remains.

When you realize how these work then you can reject a huge number of these papers out of hand when they talk about drift as many of them are bogus.