Experimental assay of a fitness landscape on a macroevolutionary scale
Victoria O. Pokusaeva,
Dinara R. Usmanova,
Ekaterina V. Putintseva,
Karen S. Sarkisyan,
Alexander S. Mishin,
Natalya S. Bogatyreva,
Dmitry N. Ivankov,
Arseniy V. Akopyan,
Sergey Ya. Avvakumov,
Inna S. Povolotskaya,
Guillaume J. Filion,
Lucas B. Carey,
Fyodor A. Kondrashov
Posted 21 Nov 2017
bioRxiv DOI: 10.1101/222778
Posted 21 Nov 2017
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. The His3 fitness landscape is dominated by synergistic epistasis. For 80% of substitutions, the effect on fitness depended on the genetic background. Furthermore, at 67% of sites, substitutions are under sign epistasis, having both strongly positive and negative effects in different genetic backgrounds. 46% of sites were under reciprocal sign epistasis. Sign epistasis affected few genotypes but involved the interaction of multiple sites which makes multidimensionality of the His3 fitness landscape essential, with the number of dimensions of the landscape approximately one quarter of the sequence length.
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