Evidence for positive epistasis in HIV-1.
Reproductive strategies such as sexual reproduction and recombination that involve the shuffling of parental genomes for the production of offspring are ubiquitous in nature. However, their evolutionary benefit remains unclear. Many theories have identified potential benefits, but progress is hampered by the scarcity of relevant data. One class of theories is based on the assumption that mutations affecting fitness exhibit negative epistasis. Retroviruses recombine frequently and thus provide a unique opportunity to test these theories. Using amino acid sequence data and fitness values from 9466 human immunodeficiency virus 1 (HIV-1) isolates, we find in contrast to these theories strong statistical evidence for a predominance of positive epistasis in HIV-1.
Bonhoeffer
Sebastian
S
Ecology and Evolution, ETH Zurich, ETH Zentrum NW, CH-8092 Zurich, Switzerland. seb@env.ethz.ch
Chappey
Colombe
C
Parkin
Neil T
NT
Whitcomb
Jeanette M
JM
Petropoulos
Christos J
CJ
D000595:Amino Acid Sequence; D000596:Amino Acids; D019380:Anti-HIV Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral; D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D016333:HIV Protease / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006801:Humans; D009154:Mutation; D011995:Recombination, Genetic; D012984:Software; D014779:Virus Replication
D000596:Amino Acids; D019380:Anti-HIV Agents; D054303:HIV Reverse Transcriptase; D016333:HIV Protease