Constrained mutational sampling of amino acid in HIV-1 protease evolution

Understand how the genetic code impacts protein evolution in HIV where most single nucleotide mutations are sampled within an infected individual. We chose to focus on protease because of a wealth of available sequence data and the relatively small size of the 99 amino acid gene facilitated experimental analyses. Despite the high mutation rate of HIV, our results indicate that the inefficiently sampling of amino acids requiring multiple nucleotide changes creates a mutational barrier such that many amino acids capable of supporting efficient viral replication are not readily available to the evolution of HIV proteins.