Long-term experimental evolution of HIV-1 reveals effects of environment and mutational history

PLoS Biol. 2020 Dec 28;18(12):e3001010. doi: 10.1371/journal.pbio.3001010. eCollection 2020 Dec.

Abstract

An often-returning question for not only HIV-1, but also other organisms, is how predictable evolutionary paths are. The environment, mutational history, and random processes can all impact the exact evolutionary paths, but to which extent these factors contribute to the evolutionary dynamics of a particular system is an open question. Especially in a virus like HIV-1, with a large mutation rate and large population sizes, evolution is expected to be highly predictable if the impact of environment and history is low, and evolution is not neutral. We investigated the effect of environment and mutational history by analyzing sequences from a long-term evolution experiment, in which HIV-1 was passaged on 2 different cell types in 8 independent evolutionary lines and 8 derived lines, 4 of which involved a switch of the environment. The experiments lasted for 240-300 passages, corresponding to approximately 400-600 generations or almost 3 years. The sequences show signs of extensive parallel evolution-the majority of mutations that are shared between independent lines appear in both cell types, but we also find that both environment and mutational history significantly impact the evolutionary paths. We conclude that HIV-1 evolution is robust to small changes in the environment, similar to a transmission event in the absence of an immune response or drug pressure. We also find that the fitness landscape of HIV-1 is largely smooth, although we find some evidence for both positive and negative epistatic interactions between mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Directed Molecular Evolution / methods
  • Evolution, Molecular*
  • Genetic Fitness / genetics
  • HIV Infections / virology
  • HIV Seropositivity
  • HIV-1 / genetics*
  • HIV-1 / metabolism*
  • Humans
  • Models, Genetic
  • Mutation / genetics
  • Mutation Rate

Grants and funding

RRR gratefully acknowledges the financial support of the Swiss National Science Foundation (www.snf.ch, grant numbers 31003A_149769 and 31003A_179170). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.