Epistasis Analysis Goes Genome-Wide

Zhang, Jianzhi

doi:10.1371/journal.pgen.1006558

Cited by 8 publications

(6 citation statements)

References 14 publications

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“…A number of evolutionary theories such as the mutational deterministic hypothesis of the evolution of sexual reproduction 2 and the hypothesis of reduction in mutational load by truncation selection against deleterious mutations depend on assumptions of general trends of epistasis 3 . Universal patterns involving epistasis are emerging from decades of intense investigations 4 , 5 . For instance, many experimental evolution studies have shown that fitness increase slows during the organismal adaptation to a constant environment 6 .…”

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Idiosyncratic epistasis creates universals in mutational effects and evolutionary trajectories

Lyons

Zou

et al. 2020

Nat Ecol Evol

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Patterns of epistasis and shapes of fitness landscapes are of wide interest because of their bearings on a number of evolutionary theories. The common phenomena of slowing fitness increases during adaptations and diminishing returns from beneficial mutations are believed to reflect a concave fitness landscape and a preponderance of negative epistasis. Paradoxically, fitness drops tend to decelerate and harm from deleterious mutations shrinks during accumulation of random mutations, patterns thought to indicate a convex fitness landscape and a predominance of positive epistasis. Current theories cannot resolve this apparent contradiction. Here we show that the phenotypic effect of a mutation varies substantially depending on the specific genetic background and that this idiosyncrasy in epistasis creates all of the above trends without requiring a biased distribution of epistasis. The idiosyncratic epistasis theory explains the universalities in mutational effects and evolutionary trajectories as emerging from randomness due to biological complexity.

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Idiosyncratic epistasis creates universals in mutational effects and evolutionary trajectories

Lyons

Zou

et al. 2020

Nat Ecol Evol

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“…The fraction of DNA sequence evolution that is adaptive equals the proportion of all substitutions that are beneficial (AF G , where AF stands for adaptive fraction and the subscript G stands for genotype). Due to prevalent epistasis (Zhang 2017) and genotype-by-environment interactions (Wei and Zhang 2017), the fitness effect of a substitution depends on both the genetic background and environment. Hence, any fitness effect discussed here refers to that in the genetic background and environment when the substitution takes place.…”

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Neutral Theory and Phenotypic Evolution

Zhang

2018

Molecular Biology and Evolution

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Although the neutral theory of molecular evolution was proposed to explain DNA and protein sequence evolution, in principle it could also explain phenotypic evolution. Nevertheless, overall, phenotypes should be less likely than genotypes to evolve neutrally. I propose that, when phenotypic traits are stratified according to a hierarchy of biological organization, the fraction of evolutionary changes in phenotype that are adaptive rises with the phenotypic level considered. Consistently, molecular traits are frequently found to evolve neutrally whereas a large, random set of organismal traits were recently reported to vary largely adaptively. Many more studies of unbiased samples of phenotypic traits are needed to test the general validity of this hypothesis.

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“…Epistasis -defined as gene-gene interaction -has been found to play an important role in the etiology of complex diseases [1][2][3]. Epistasis is an important factor in shaping genetic variance within and between populations, and consequently phenotypic variation [1,[4][5][6]; epistasits is further considered to be one potential explanations of missing heritability in genome-wide association studies (GWAS) [7,8].…”

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Detecting fitness epistasis in recently admixed populations with genome-wide data

Zhou

Wang

et al. 2020

BMC Genomics

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Background: Fitness epistasis, the interaction effect of genes at different loci on fitness, makes an important contribution to adaptive evolution. Although fitness interaction evidence has been observed in model organisms, it is more difficult to detect and remains poorly understood in human populations as a result of limited statistical power and experimental constraints. Fitness epistasis is inferred from non-independence between unlinked loci. We previously observed ancestral block correlation between chromosomes 4 and 6 in African Americans. The same approach fails when examining ancestral blocks on the same chromosome due to the strong confounding effect observed in a recently admixed population. Results: We developed a novel approach to eliminate the bias caused by admixture linkage disequilibrium when searching for fitness epistasis on the same chromosome. We applied this approach in 16,252 unrelated African Americans and identified significant ancestral correlations in two pairs of genomic regions (P-value< 8.11 × 10 − 7) on chromosomes 1 and 10. The ancestral correlations were not explained by population admixture. Historical African-European crossover events are reduced between pairs of epistatic regions. We observed multiple pairs of coexpressed genes shared by the two regions on each chromosome, including ADAR being co-expressed with IFI44 in almost all tissues and DARC being co-expressed with VCAM1, S1PR1 and ELTD1 in multiple tissues in the Genotype-Tissue Expression (GTEx) data. Moreover, the co-expressed gene pairs are associated with the same diseases/traits in the GWAS Catalog, such as white blood cell count, blood pressure, lung function, inflammatory bowel disease and educational attainment. Conclusions: Our analyses revealed two instances of fitness epistasis on chromosomes 1 and 10, and the findings suggest a potential approach to improving our understanding of adaptive evolution.

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Epistasis Analysis Goes Genome-Wide

Cited by 8 publications

References 14 publications

Idiosyncratic epistasis creates universals in mutational effects and evolutionary trajectories

Idiosyncratic epistasis creates universals in mutational effects and evolutionary trajectories

Neutral Theory and Phenotypic Evolution

Detecting fitness epistasis in recently admixed populations with genome-wide data

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