The paper I wrote with Sergey Kryazhimskiy and John Wakeley (both at Harvard) came out this week in PLoS Genetics. In the paper we describe how genetic diversity is lost and recovered in HIV populations that evolve and become drug resistant. This was possible because of a dataset that was collected in the late 1990s. This dataset is unique because it has multiple sequences of the protease and reverse transcriptase regions at multiple time points for many patients. We found evidence for soft and hard sweeps.
Meredith Carpenter (Stanford) wrote a very nice blog post about the paper.
Download the paper with the supplementary materials here: 2014PennKryWakeleyPGeneticsWSupplMat
The Molecular Ecologist is a blog written by a group of authors and linked to the journals Molecular Ecology and Molecular Ecology Resources.
Today The Molecular Ecologist published an interview with me. I am honored to be only the fourth person featured in their “People behind the science” series, after Loren Riesenberg (editor in chief for Molecular Ecology), Ruth Shaw (editor in chief for Evolution) and Richard Lenski. The interview series is the work of John Stanton-Geddes (his website is worth a look, especially if you like open science).
Update (Dec 19th 2013): just got news that “The Microbial Population Biology Gordon Research Seminar (GRS) has been scheduled to take place July 18-19, 2015 at Proctor Academy, Andover, NH. The Microbial Population Biology GRC will take place July 19-24, 2015 at the same location.”
Many Gordon Research Conferences now start with a Gordon Research Seminar. The GRSeminar is a smaller meeting only for the graduate students and postdocs who will attend the GRConference. Last summer I went to the Microbial Population Biology GRConference and the GRSeminar that occurred before it.
I thought the GRSeminar was a really nice way to start the week, because there were fewer people and no famous professors (except two invited speakers) so the graduate students and postdocs could focus on getting to know each other. Although the GRSeminar only lasted for about 24 hours, I still think it had a very positive effect on the rest of the week.
At the end of the GRConference I was asked to be the chair of the next GRSeminar on Microbial Population Biology that will accompany the GRConference on the same topic in 2015. Three people offered to help me with organizing the next GRSeminar (Krishna Swamy, Elizabeth Jerison and Helena Mendes-Soares) so we’ll be working as a team. Michael Travisano is the chair of the 2015 GRConference. Last week we heard that the GRC organization approved our request to have another GRSeminar, so I’ll be traveling to LA in January to learn all I need to know to be a good GRSeminar chair.
An editorial I wrote with Bob Shafer and Susan Holmes (both Stanford) got published this week in Journal of Infectious Disease. See here.
The editorial is about a recent paper by Joel Wertheim and colleagues who analyze 80,000 HIV sequences to characterize the worldwide HIV epidemic.
I wrote a blog post about it here.
A short review on F1000 said: “This is an editorial commentary that provides an excellent summary of the use and limitations of HIV viral phylogenetics to understand transmission and sexual networks.”
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”.
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.
The video I wrote about earlier on this website (here) won the NESCent film festival! The NESCent film festival, which showcased the movies sent to the “third annual Evolution Video Competition” took place at the Evolution conference in Snowbird, Utah.
Thanks to my colleagues Tobias Pamminger, Susanne Foitzik and Dirk Metzler for the ongoing ant collaboration.
Together with Sarah Cobey I am hosting a NESCent working group on “Trends in the evolution of human viruses.” See NESCent website.
Abstract: Many of the most exciting concepts in biology, including selection and neutrality, asexual and sexual reproduction, stochastic and deterministic dynamics, and the interplay of ecology and evolution can be studied through the lens of host-pathogen interactions. Some of the best studied pathogens are viruses that infect humans, although research has focused disproportionately on a few viruses that constitute only a small fraction of the infectious disease burden on humans. The aim of this working group is to broaden our perspective on host-pathogen interactions by synthesizing observations of the evolution of the most prevalent human viruses and asking whether commonalities and differences between evolutionary patterns can be readily explained by current theory. In particular, we will seek to augment the traditional emphasis on genotype and sequence-level analysis with information on viral phenotypes. We will also investigate whether the phylodynamic framework, which proposes that viral phylogenies are chiefly shaped by immune pressure and epidemic dynamics, provides a good approximation of the dominant evolutionary modes of less well studied viruses. Our findings will help identify gaps in the study of viral evolution and aggregate observations for the development and testing of theory.
Sarah Cobey is an assistant professor at the University of Chicago. Before that she was a post doc at the Harvard School of Public Health. I met Sarah in 2005 when we were both part of the Young Scientists Summer Program of IIASA in Vienna. Her website is here.