Epistasis constrains mutational pathways of hemoglobin adaptation in high-altitude pikas.

ABSTRACT: A fundamental question in evolutionary genetics concerns the roles of mutational pleiotropy and epistasis in shaping trajectories of protein evolution. This question can be addressed most directly by using site-directed mutagenesis to explore the mutational landscape of protein function in experimentally defined regions of sequence space. Here, we evaluate how pleiotropic trade-offs and epistatic interactions influence the accessibility of alternative mutational pathways during the adaptive evolution of hemoglobin (Hb) function in high-altitude pikas (Mammalia: Lagomorpha). By combining ancestral protein resurrection with a combinatorial protein-engineering approach, we examined the functional effects of sequential mutational steps in all possible pathways that produced an increased Hb-O2

SUBMITTER: Tufts DM 

PROVIDER: S-EPMC4298171 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature