The clarifying role of time series data in the population genetics of HIV
Fig 1
Cartoon of explanations for post-sweep diversity loss patterns observed in Feder et al. [11].
We seek to explain why more diversity is retained following the fixation of drug resistance to early, ineffective therapies than modern, effective ones. The soft sweeps of recurrent mutations hypothesis [11] suggest that the primary difference is that θ is high for ineffective drugs, leading to short waiting times between resistance mutations and subsequent soft sweeps (top left), whereas θ is lower for effective drugs, leading to long waiting times between resistance mutations subsequent and hard sweeps (bottom left). The recombination-rescued diversity hypothesis [12] suggests that the primary difference is the opportunity for recombination to rescue diversity following a beneficial mutation: Sweeps in response to ineffective drugs are slow and occur after wider population bottlenecks, which gives recombination time to rescue diversity (top right). Sweeps in response to effective drugs are fast and occur after narrow population bottlenecks, so recombination has less opportunity to rescue genetic diversity (bottom right). Stars represent drug resistance mutations entering the population de novo and drug pressure starts at the x-intercept.