An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape.

Autor: 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
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: PLoS Genetics, Vol 15, Iss 4, p e1008079 (2019)
Druh dokumentu: article
ISSN: 1553-7390
1553-7404
DOI: 10.1371/journal.pgen.1008079
Popis: 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.
Databáze: Directory of Open Access Journals
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