+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Epistasis in protein evolution

Epistasis in protein evolution

Protein Science 25(7): 1204-1218

The structure, function, and evolution of proteins depend on physical and genetic interactions among amino acids. Recent studies have used new strategies to explore the prevalence, biochemical mechanisms, and evolutionary implications of these interactions-called epistasis-within proteins. Here we describe an emerging picture of pervasive epistasis in which the physical and biological effects of mutations change over the course of evolution in a lineage-specific fashion. Epistasis can restrict the trajectories available to an evolving protein or open new paths to sequences and functions that would otherwise have been inaccessible. We describe two broad classes of epistatic interactions, which arise from different physical mechanisms and have different effects on evolutionary processes. Specific epistasis-in which one mutation influences the phenotypic effect of few other mutations-is caused by direct and indirect physical interactions between mutations, which nonadditively change the protein's physical properties, such as conformation, stability, or affinity for ligands. In contrast, nonspecific epistasis describes mutations that modify the effect of many others; these typically behave additively with respect to the physical properties of a protein but exhibit epistasis because of a nonlinear relationship between the physical properties and their biological effects, such as function or fitness. Both types of interaction are rampant, but specific epistasis has stronger effects on the rate and outcomes of evolution, because it imposes stricter constraints and modulates evolutionary potential more dramatically; it therefore makes evolution more contingent on low-probability historical events and leaves stronger marks on the sequences, structures, and functions of protein families.

(PDF emailed within 0-6 h: $19.90)

Accession: 057784653

Download citation: RISBibTeXText

PMID: 26833806

DOI: 10.1002/pro.2897

Related references

Protein evolution. Pervasive degeneracy and epistasis in a protein-protein interface. Science 347(6222): 673-677, 2015

How mutational epistasis impairs predictability in protein evolution and design. Protein Science 25(7): 1260-1272, 2017

Crystal structure of an ancient protein: evolution by conformational epistasis. Science 317(5844): 1544-1548, 2007

Stability-mediated epistasis constrains the evolution of an influenza protein. Elife 2: E00631, 2013

Estimating the contribution of folding stability to nonspecific epistasis in protein evolution. Proteins 2018, 2018

No Evidence That Protein Noise-Induced Epigenetic Epistasis Constrains Gene Expression Evolution. Molecular Biology and Evolution 34(2): 380-390, 2016

The Evolution of Canalization and the Breaking of Von Baer's Laws: Modeling the Evolution of Development with Epistasis. Evolution; International Journal of Organic Evolution 52(3): 647-656, 1998

The evolution of canalization and the breaking of von Baer's law: Modeling the evolution of development with epistasis. Evolution 52(3): 647-656, 1998

Evolution. Epistasis in RNA viruses. Science 306(5701): 1492-1493, 2004

Rate of evolution of a character without epistasis. Proceedings of the National Academy of Sciences of the United States of America 86(6): 1910-1913, 1989

Evolution can favor antagonistic epistasis. Genetics 177(2): 1001-1010, 2007

Epistasis and the Evolution of Antimicrobial Resistance. Frontiers in Microbiology 8: 246, 2017

On the evolution of epistasis I: diploids under selection. Theoretical Population Biology 67(3): 141-160, 2005

QTL-based evidence for the role of epistasis in evolution. Genetical Research 86(2): 89-95, 2005

Pervasive cryptic epistasis in molecular evolution. Plos Genetics 6(10): E1001162, 2011