Exploring the Effect of Sex on Empirical Fitness Landscapes

Visser, Jaap; Park, Su‐Chan; Krug, Joachim

doi:10.1086/599081

Cited by 141 publications

(202 citation statements)

References 51 publications

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“…Although the withinpatient census population size of HIV-1 is large, on the order of 10 7 infected cells (Chun et al 1997), estimates of the effective population size range from 10 2 to 10 5 (e.g., Leigh Brown 1997; Rouzine and Coffin 1999;Seo et al 2002;Achaz et al 2004;Shriner et al 2004;Kouyos et al 2006). A high rate of recombination, as observed for HIV-1 (Jung et al 2002;Levy et al 2004), is also unlikely to help because high recombination is expected to reduce the rate of adaptation on rugged fitness landscapes de Visser et al 2009). However, because V3 is the primary target of neutralizing antibodies (Zolla-Pazner 2004), fluctuating selection by antibodies (Richman et al 2003;Wei et al 2003) could change the fitness landscape so that some trajectories become selectively accessible.…”

Section: Discussionmentioning

confidence: 99%

Fitness Epistasis and Constraints on Adaptation in a Human Immunodeficiency Virus Type 1 Protein Region

et al. 2010

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Fitness epistasis, the interaction among alleles at different loci in their effects on fitness, has potentially important consequences for adaptive evolution. We investigated fitness epistasis among amino acids of a functionally important region of the human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein (gp120). Seven mutations putatively involved in the adaptation of the second conserved to third variable protein region (C2-V3) to the use of an alternative host-cell chemokine coreceptor (CXCR4) for cell entry were engineered singly and in combinations on the wild-type genetic background and their effects on viral infectivity were measured. Epistasis was found to be common and complex, involving not only pairwise interactions, but also higher-order interactions. Interactions could also be surprisingly strong, changing fitness by more than 9 orders of magnitude, which is explained by some single mutations being practically lethal. A consequence of the observed epistasis is that many of the minimum-length mutational trajectories between the wild type and the mutant with highest fitness on cells expressing the alternative coreceptor are selectively inaccessible. These results may help explain the difficulty of evolving viruses that use the alternative coreceptor in culture and the delayed evolution of this phenotype in natural infection. Knowledge of common, complex, and strong fitness interactions among amino acids is necessary for a full understanding of protein evolution.

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Section: Discussionmentioning

confidence: 99%

Fitness Epistasis and Constraints on Adaptation in a Human Immunodeficiency Virus Type 1 Protein Region

et al. 2010

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“…Similarly, recombination may or may not provide an advantage under directional selection. Various work in population genetic theory and experimental observations demonstrate such an advantage (Fisher 1930;Muller 1932;Felsenstein 1974;de Visser et al 1999;Wilke 2004;Keightley and Otto 2006;Cooper 2007), although this advantage may not be universal (de Visser et al 2008). In a model of gene regulatory circuits closely related to the one considered here, recombination modifiers that increase the recombination rate do not readily become established in populations (MacCarthy and Bergman 2007).…”

Section: Discussionmentioning

confidence: 99%

Effects of Recombination on Complex Regulatory Circuits

Martin

Wagner

2009

Genetics

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Mutation and recombination are the two main forces generating genetic variation. Most of this variation may be deleterious. Because recombination can reorganize entire genes and genetic circuits, it may have much greater consequences than point mutations. We here explore the effects of recombination on models of transcriptional regulation circuits that play important roles in embryonic development. We show that recombination has weaker deleterious effects on the expression phenotypes of these circuits than mutations. In addition, if a population of such circuits evolves under the influence of mutation and recombination, we find that three key properties emerge: (1) deleterious effects of mutations are reduced dramatically; (2) the diversity of genotypes in the population is greatly increased, a feature that may be important for phenotypic innovation; and (3) cis-regulatory complexes appear. These are combinations of regulatory interactions that influence the expression of one gene and that mitigate deleterious recombination effects.

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“…This result led the authors to conclude that the adaptive landscape was smooth. Additional studies using different approaches (e.g., tracking diversity across replicates, engineering a small sliver of the landscape) have found support for both rugged (24)(25)(26)(27) and smooth (4,(26)(27)(28)(29)(30) topographies.…”

Section: Significancementioning

confidence: 99%

A tortoise–hare pattern seen in adapting structured and unstructured populations suggests a rugged fitness landscape in bacteria

Nahum

Godfrey‐Smith

Harding

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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In the context of Wright's adaptive landscape, genetic epistasis can yield a multipeaked or "rugged" topography. In an unstructured population, a lineage with selective access to multiple peaks is expected to fix rapidly on one, which may not be the highest peak. In a spatially structured population, on the other hand, beneficial mutations take longer to spread. This slowdown allows distant parts of the population to explore the landscape semiindependently. Such a population can simultaneously discover multiple peaks, and the genotype at the highest discovered peak is expected to dominate eventually. Thus, structured populations sacrifice initial speed of adaptation for breadth of search. As in the fable of the tortoise and the hare, the structured population (tortoise) starts relatively slow but eventually surpasses the unstructured population (hare) in average fitness. In contrast, on singlepeak landscapes that lack epistasis, all uphill paths converge. Given such "smooth" topography, breadth of search is devalued and a structured population only lags behind an unstructured population in average fitness (ultimately converging). Thus, the tortoise-hare pattern is an indicator of ruggedness. After verifying these predictions in simulated populations where ruggedness is manipulable, we explore average fitness in metapopulations of Escherichia coli. Consistent with a rugged landscape topography, we find a tortoise-hare pattern. Further, we find that structured populations accumulate more mutations, suggesting that distant peaks are higher. This approach can be used to unveil landscape topography in other systems, and we discuss its application for antibiotic resistance, engineering problems, and elements of Wright's shifting balance process.adaptive landscape | experimental evolution | NK model | landscape topography | spatial structure

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Exploring the Effect of Sex on Empirical Fitness Landscapes

Cited by 141 publications

References 51 publications

Fitness Epistasis and Constraints on Adaptation in a Human Immunodeficiency Virus Type 1 Protein Region

Fitness Epistasis and Constraints on Adaptation in a Human Immunodeficiency Virus Type 1 Protein Region

Effects of Recombination on Complex Regulatory Circuits

A tortoise–hare pattern seen in adapting structured and unstructured populations suggests a rugged fitness landscape in bacteria

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