TY - JOUR T1 - Exploring the Complexity of the HIV-1 Fitness Landscape A1 - Kouyos, Roger D. A1 - Leventhal, Gabriel E. A1 - Hinkley, Trevor A1 - Haddad, Mojgan A1 - Whitcomb, Jeannette M. A1 - Petropoulos, Christos J. A1 - Bonhoeffer, Sebastian Y1 - 2012/03/08 N2 - Author Summary Evolutionary adaptation can be understood as populations moving uphill on landscapes, in which height corresponds to evolutionary fitness. Although such fitness landscapes are central to evolutionary theory, there is currently a lack of biologically realistic examples. Here we analyze large-scale fitness landscapes derived from in vitro fitness measurements of HIV-1. We find that these landscapes are very rugged and that, accordingly, adaptive processes on these landscapes depend sensitively on the initial conditions. Moreover, the landscapes contain large networks along which fitness changes only minimally. While the relative extent to which mutations affect fitness on their own or in combination with other mutations is a strong determinant of these properties, the fitness landscape of HIV-1 is considerably less rugged than expected from the individual and pair-wise effects of mutations. Overall this study confirms theoretical conjectures about the complexity of biological fitness landscapes and the importance of the high dimensionality of the genetic space in which adaptation takes place. JF - PLOS Genetics JA - PLOS Genetics VL - 8 IS - 3 UR - https://doi.org/10.1371/journal.pgen.1002551 SP - e1002551 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pgen.1002551 ER -