Should evolutionary geneticists worry about higher-order epistasis?

Weinreich, Daniel; Lan, Yinghong; Wylie, C. Scott; Heckendorn, Robert B.

doi:10.1016/j.gde.2013.10.007

Cited by 280 publications

(439 citation statements)

References 54 publications

(61 reference statements)

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“…The partial incompatibility due to each gene is itself attributable to epistatic interactions among sites in or near the gene, as expected of ongoing evolution through slightly deleterious mutations compensated by other mutations elsewhere in the gene (39). The number of interacting sites could be as few as two, but experimental evidence implies that higher-order interactions are more likely (40,41). Considering the within-gene interactions and the effects of environment and genetic background (30), hybrid male sterility in this case behaves like a classical quantitative trait affected by multiple genes with relatively small effects (42) as well as environmental factors.…”

Section: Discussionmentioning

confidence: 99%

Neighboring genes for DNA-binding proteins rescue male sterility in Drosophila hybrids

Liénard

Araripe

Hartl

2016

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

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Crosses between closely related animal species often result in male hybrids that are sterile, and the molecular and functional basis of genetic factors for hybrid male sterility is of great interest. Here, we report a molecular and functional analysis of HMS1, a region of 9.2 kb in chromosome 3 of Drosophila mauritiana, which results in virtually complete hybrid male sterility when homozygous in the genetic background of sibling species Drosophila simulans. The HMS1 region contains two strong candidate genes for the genetic incompatibility, agt and Taf1. Both encode unrelated DNA-binding proteins, agt for an alkyl-cysteine-S-alkyltransferase and Taf1 for a subunit of transcription factor TFIID that serves as a multifunctional transcriptional regulator. The contribution of each gene to hybrid male sterility was assessed by means of germ-line transformation, with constructs containing complete agt and Taf1 genomic sequences as well as various chimeric constructs. Both agt and Taf1 contribute about equally to HMS1 hybrid male sterility. Transgenes containing either locus rescue sterility in about one-half of the males, and among fertile males the number of offspring is in the normal range. This finding suggests compensatory proliferation of the rescued, nondysfunctional germ cells. Results with chimeric transgenes imply that the hybrid incompatibilities result from interactions among nucleotide differences residing along both agt and Taf1. Our results challenge a number of preliminary generalizations about the molecular and functional basis of hybrid male sterility, and strongly reinforce the role of DNA-binding proteins as a class of genes contributing to the maintenance of postzygotic reproductive isolation.postzygotic reproductive isolation | hybrid male sterility | gene conflict | transcription factor

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Section: Discussionmentioning

confidence: 99%

Neighboring genes for DNA-binding proteins rescue male sterility in Drosophila hybrids

Liénard

Araripe

Hartl

2016

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

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“…To confirm the presence of higher-order epistasis, we decomposed the fitness landscape by Fourier analysis (see Materials and methods, Figure 3-figure supplement 1) Weinreich et al, 2013;Neidhart et al, 2013). The Fourier coefficients can be interpreted as epistatic interactions of different orders (Weinreich et al, 2013;de Visser and Krug, 2014), including the main effects of single mutations (the first order), pairwise epistasis (the second order), and higher-order epistasis (the third and the fourth order).…”

Section: Evidence and Impacts Of Higher-order Epistasismentioning

confidence: 99%

“…The Fourier coefficients can be interpreted as epistatic interactions of different orders (Weinreich et al, 2013;de Visser and Krug, 2014), including the main effects of single mutations (the first order), pairwise epistasis (the second order), and higher-order epistasis (the third and the fourth order). The fitness of variants can be reconstructed by expansion of Fourier coefficients up to a certain order (Figure 3-figure supplement 2).…”

Section: Evidence and Impacts Of Higher-order Epistasismentioning

confidence: 99%

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Adaptation in protein fitness landscapes is facilitated by indirect paths

Dai

Olson

et al. 2016

Preprint

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The structure of fitness landscapes is critical for understanding adaptive protein evolution. Previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph involving only two amino acids at each site. In reality, the dimensionality of protein sequence space is higher (20 L ) and there may be higher-order interactions among more than two sites. Here we experimentally characterized the fitness landscape of four sites in protein GB1, containing 20 4 = 160,000 variants. We found that while reciprocal sign epistasis blocked many direct paths of adaptation, such evolutionary traps could be circumvented by indirect paths through genotype space involving gain and subsequent loss of mutations. These indirect paths alleviate the constraint on adaptive protein evolution, suggesting that the heretofore neglected dimensions of sequence space may change our views on how proteins evolve.

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“…Indeed, the number of peaks in a landscape ultimately depends on whether mutations interact multiplicatively or epistatically in determining fitness [3]. Especially, if epistasis takes the form of sign [6] or reciprocal sign [7], landscapes are highly rugged and the number of accessible pathways will be limited [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Efficient escape from local optima in a highly rugged fitness landscape by evolving RNA virus populations

2016

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Predicting viral evolution has proven to be a particularly difficult task, mainly owing to our incomplete knowledge of some of the fundamental principles that drive it. Recently, valuable information has been provided about mutation and recombination rates, the role of genetic drift and the distribution of mutational, epistatic and pleiotropic fitness effects. However, information about the topography of virus' adaptive landscapes is still scarce, and to our knowledge no data has been reported so far on how its ruggedness may condition virus' evolvability. Here, we show that populations of an RNA virus move efficiently on a rugged landscape and scape from the basin of attraction of a local optimum. We have evolved a set of Tobacco etch virus genotypes located at increasing distances from a local adaptive optimum in a highly rugged fitness landscape, and we observed that few evolved lineages remained trapped in the local optimum, while many others explored distant regions of the landscape. Most of the diversification in fitness among the evolved lineages was explained by adaptation, while historical contingency and chance events contribution was less important. Our results demonstrate that the ruggedness of adaptive landscapes is not an impediment for RNA viruses to efficiently explore remote parts of it.

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Should evolutionary geneticists worry about higher-order epistasis?

Cited by 280 publications

References 54 publications

Neighboring genes for DNA-binding proteins rescue male sterility in Drosophila hybrids

Neighboring genes for DNA-binding proteins rescue male sterility in Drosophila hybrids

Adaptation in protein fitness landscapes is facilitated by indirect paths

Efficient escape from local optima in a highly rugged fitness landscape by evolving RNA virus populations

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