224W Poster - Population Genetics
Wednesday June 08, 8:30 PM - 9:15 PM

Authors:
Chenlu Di ¹; Jesús Murga-Moreno ²; David Enard ¹

Affiliations:
1) University of Arizona; 2) Autonomous University of Barcelona

Keywords:
Natural selection

A large proportion of protein adaptation in human evolution was driven by past viral infections. It is not clear however what effects adaptive amino acid changes had on host proteins that were advantageous against viruses. We hypothesize that viral-interacting host proteins adapted in response to viruses through changes in protein thermodynamic stability, or the balance between the folded and unfolded state of proteins. Protein stability is an important property broadly studied in biophysics, protein engineering and drug design. A destabilizing amino acid change can decrease the proportion of folded functional proteins at physiological temperature, and might thus reduce the protein function of a proviral host protein that a virus needs to complete its cycle. Conversely, adaptive amino-acid changes may stabilize and thus increase the amount of a host antiviral protein. We used an Approximate Bayesian Computation version of the McDonald-Kreitman test called ABC-MK to compare the rate of adaption in human proteins between amino acid changes that strongly changed protein stability and changes that do not. Our results suggest that a large amount of protein adaptation to viruses was driven by changes in protein stability, rather than the classic assumption of adaptation at the host-virus contact interface.