Epistasis Blog

From the Artificial Intelligence Innovation Lab at Cedars-Sinai Medical Center (www.epistasis.org)

Monday, August 22, 2016

Nuclear-mitochondrial epistasis

So much potential here for human genetics!

Wade MJ, Drown DM. Nuclear-mitochondrial epistasis: a gene's eye view of genomic conflict. Ecol Evol. 2016 Aug 18;6(18):6460-6472. [PubMed]


We use population genetic models to investigate the cooperative and conflicting synergistic fitness effects between genes from the nucleus and the mitochondrion. By varying fitness parameters, we examine the scope for conflict relative to cooperation among genomes and the utility of the "gene's eye view" analytical approach, which is based on the marginal average fitness of specific alleles. Because sexual conflict can maintain polymorphism of mitochondrial haplotypes, we can explore two types of evolutionary conflict (genomic and sexual) with one epistatic model. We find that the nuclear genetic architecture (autosomal, X-linked, or Z-linked) and the mating system change the regions of parameter space corresponding to the evolution by sexual and genomic conflict. For all models, regardless of conflict or cooperation, we find that population mean fitness increases monotonically as evolution proceeds. Moreover, we find that the process of gene frequency change with positive, synergistic fitnesses is self-accelerating, as the success of an allele in one genome or in one sex increases the frequency of the interacting allele upon which its success depends. This results in runaway evolutionary dynamics caused by the positive intergenomic associations generated by selection. An inbreeding mating system tends to further accelerate these runaway dynamics because it maintains favorable host-symbiont or male-female gene combinations. In contrast, where conflict predominates, the success of an allele in one genome or in one sex diminishes the frequency of the corresponding allele in the other, resulting in considerably slower evolutionary dynamics. The rate of change of mean fitness is also much faster with positive, synergistic fitnesses and much slower where conflict is predominant. Consequently, selection rapidly fixes cooperative gene combinations, while leaving behind a slowing evolving residue of conflicting gene combinations at mutation-selection balance. We discuss how an emphasis on marginal fitness averages may obscure the interdependence of allelic fitness across genomes, making the evolutionary trajectories appear independent of one another when t
hey are not.


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