Paper on sweeps in HIV accepted by PLoS Genetics

29 Oct

Last week, we got news that our paper on “Loss and recovery of genetic variation in adapting HIV populations” is accepted for publication in PLoS Genetics! My coauthors on this paper are Sergey Kryazhimskiy and John Wakeley. You can find an earlier version of the paper on the arXiv, and a related blog post on Haldane’s Sieve.

In a nutshell, this is what the paper is about: we analyze longitudinal data on 30 patients in which the virus evolves to become drug resistant. We see that

1. known resistance mutations mostly fix one at a time,

2. these fixations are associated with a reduction in genetic diversity due to hitchhiking,

3. the fixations involve both soft and hard sweeps (see pictures), and

4. recovery of genetic diversity is slow for synonymous sites and faster for non-synonymous sites.

Soft selective sweep in HIV. The K103N substitution is caused by an A to T or A to C mutation. In this patient both alleles are present. A clear example of a "multiple-origin soft sweep".

Soft selective sweep in HIV. The K103N substitution is caused by an A to T or A to C mutation. In this patient both alleles are present. A clear example of a “multiple-origin soft sweep”.

Selective sweep in HIV. An NNRTI drug resistance mutation (K103N) goes to fixation in patient virus. The mutation (A to T) apparently occurred on one haplotype (genetic background) and as it went to fixation, genetic variation on was lost. Not all sweeps in HIV are hard sweeps, see next figure.

Selective sweep in HIV. An NNRTI drug resistance mutation (K103N) goes to fixation in patient virus. The mutation (A to T) apparently occurred on one haplotype (genetic background) and as it went to fixation, genetic variation on was lost.

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