An Experimental Assay of the Interactions of Amino Acids from Orthologous Sequences Shaping a Complex Fitness Landscape

Overview

Journal PLoS Genet

Specialty Genetics

Date 2019 Apr 11

PMID 30969963

Citations 46

Authors

Victoria O Pokusaeva

Dinara R Usmanova

Ekaterina V Putintseva

Lorena Espinar

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

Affiliations

Soon will be listed here.

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, amino acid replacements were under sign epistasis, having both strongly positive and negative effect in different genetic backgrounds. 46% of sites were under reciprocal sign epistasis. The fitness impact of amino acid replacements was influenced by only a few genetic backgrounds 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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