TY - JOUR
T1 - An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape
AU - Pokusaeva, Victoria O.
AU - Usmanova, Dinara R.
AU - Putintseva, Ekaterina V.
AU - Espinar, Lorena
AU - Sarkisyan, Karen S.
AU - Mishin, Alexander S.
AU - Bogatyreva, Natalya S.
AU - Ivankov, Dmitry N.
AU - Akopyan, Arseniy V.
AU - Avvakumov, Sergey Ya
AU - Povolotskaya, Inna S.
AU - Filion, Guillaume J.
AU - Carey, Lucas B.
AU - Kondrashov, Fyodor A.
N1 - Publisher Copyright:
© 2019 Pokusaeva et al.
PY - 2019/4
Y1 - 2019/4
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85065113425
U2 - 10.1371/journal.pgen.1008079
DO - 10.1371/journal.pgen.1008079
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C2 - 30969963
AN - SCOPUS:85065113425
SN - 1553-7390
VL - 15
JO - PLoS Genetics
JF - PLoS Genetics
IS - 4
M1 - e1008079
ER -