Loss and Recovery of Genetic Diversity in Adapting Populations of HIV
Pleuni Pennings, Sergey Kryazhimskiy, John Wakeley
(Submitted on 15 Mar 2013)
A population’s adaptive potential is the likelihood that it will adapt in response to an environmental challenge, e.g., develop resistance in response to drug treatment. The effective population size inferred from genetic diversity at neutral sites has been traditionally taken as a major predictor of adaptive potential. However recent studies demonstrate that such effective population size vastly underestimates the population’s adaptive potential (Karasov 2010).
Here we use data from treated HIV-infected patients (Bacheler2000) to estimate the effective size of HIV populations relevant for adaptation. Our estimate is based on the frequencies of soft and hard selective sweeps of a known resistance mutation K103N. We observe that 41% of HIV populations in this study acquire resistance via at least two functionally equivalent but distinct mutations which sweep to fixation without significantly reducing genetic diversity at neighboring sites (soft selective sweeps). We further estimate that 20% of populations acquire a resistant allele via a single mutation that sweeps to fixation and drastically reduces genetic diversity (hard selective sweeps). We infer that the effective population size that determines the adaptive potential of within-patient HIV populations is approximately 150,000. Our estimate is two orders of magniture higher than a classical estimate based on diversity at synonymous sites.
Three not mutually exclusive reasons can explain this discrepancy:
(1) some synonymous mutations may be under selection;
(2) highly beneficial mutations may be less affected by ongoing linked selection than synonymous mutations; and
(3) synonymous diversity may not be at its expected equilibrium because it recovers slowly from sweeps and bottlenecks.