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

V. Pokusaeva, D.R. Usmanova, E.V. Putintseva, L. Espinar, K. Sarkisyan, A.S. Mishin, N.S. Bogatyreva, D. Ivankov, A. Akopyan, S. Avvakumov, I.S. Povolotskaya, G.J. Filion, L.B. Carey, F. Kondrashov, PLoS Genetics 15 (2019) e1008079.

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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, 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.
Publishing Year
Date Published
2019-04-10
Journal Title
PLoS Genetics
Volume
15
Issue
4
Article Number
e1008079
eISSN
IST-REx-ID

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Pokusaeva V, Usmanova DR, Putintseva EV, et al. An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape. PLoS Genetics. 2019;15(4):e1008079. doi:10.1371/journal.pgen.1008079
Pokusaeva, V., Usmanova, D. R., Putintseva, E. V., Espinar, L., Sarkisyan, K., Mishin, A. S., … Kondrashov, F. (2019). An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape. PLoS Genetics, 15(4), e1008079. https://doi.org/10.1371/journal.pgen.1008079
Pokusaeva, Victoria, Dinara R. Usmanova, Ekaterina V. Putintseva, Lorena Espinar, Karen Sarkisyan, Alexander S. Mishin, Natalya S. Bogatyreva, et al. “An Experimental Assay of the Interactions of Amino Acids from Orthologous Sequences Shaping a Complex Fitness Landscape.” PLoS Genetics 15, no. 4 (2019): e1008079. https://doi.org/10.1371/journal.pgen.1008079.
V. Pokusaeva et al., “An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape,” PLoS Genetics, vol. 15, no. 4, p. e1008079, 2019.
Pokusaeva V, Usmanova DR, Putintseva EV, Espinar L, Sarkisyan K, Mishin AS, Bogatyreva NS, Ivankov D, Akopyan A, Avvakumov S, Povolotskaya IS, Filion GJ, Carey LB, Kondrashov F. 2019. An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape. PLoS Genetics. 15(4), e1008079.
Pokusaeva, Victoria, et al. “An Experimental Assay of the Interactions of Amino Acids from Orthologous Sequences Shaping a Complex Fitness Landscape.” PLoS Genetics, vol. 15, no. 4, Public Library of Science, 2019, p. e1008079, doi:10.1371/journal.pgen.1008079.
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