Experimental assay of a fitness landscape on a macroevolutionary scale

Pokusaeva, V.; Usmanova, D.; Putintseva, E.; Espinar, L.; Sarkisyan, K.; Mishin, A.; Bogatyreva, N.; Ivankov, D.; Filion, G.; Carey, L.; Kondrashov, F. A.

doi:10.1101/222778

bioRxiv · 10.1101/222778

Experimental assay of a fitness landscape on a macroevolutionary scale

Pokusaeva, V.·Usmanova, D.·Putintseva, E.·Espinar, L.·Sarkisyan, K.·Mishin, A.·Bogatyreva, N.·Ivankov, D.·Filion, G.·Carey, L.·Kondrashov, F. A.

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Abstract

Characterizing the fitness landscape, a representation of fitness for a large set of genotypes, is key to understanding how genetic information is interpreted to create functional organisms. Here we determined the evolutionarily-relevant segment of the fitness landscape of His3, a gene coding for an enzyme in the histidine synthesis pathway, focusing on combinations of amino acid states found at orthologous sites of extant species. Just 15% of amino acids found in yeast His3 orthologues were always neutral while the impact on fitness of the remaining 85% depended on the genetic background. Furthermore, at 67% of sites, substitutions are under sign epistasis, having both strongly positive and negative effect in different genetic backgrounds. 46% of sites were under reciprocal sign epistasis. Sign epistasis affected few genotypes but involved interaction of multiple sites, shaping a rugged fitness landscape in which many of the shortest paths between highly fit genotypes are inaccessible.

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Pokusaeva, V., Usmanova, D., Putintseva, E., Espinar, L., Sarkisyan, K., Mishin, A., Bogatyreva, N., Ivankov, D., Filion, G., Carey, L., Kondrashov, F. A.. 2017-11-21. Experimental assay of a fitness landscape on a macroevolutionary scale. https://doi.org/10.1101/222778

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