Evolutionary and functional lessons from human-specific amino acid substitution matrices.

ABSTRACT: Human genetic variation in coding regions is fundamental to the study of protein structure and function. Most methods for interpreting missense variants consider substitution measures derived from homologous proteins across different species. In this study, we introduce human-specific amino acid (AA) substitution matrices that are based on genetic variations in the modern human population. We analyzed the frequencies of >4.8M single nucleotide variants (SNVs) at codon and AA resolution and compiled human-centric substitution matrices that are fundamentally different from classic cross-species matrices (e.g. BLOSUM, PAM). Our matrices are asymmetric, with some AA replacements showing significant directional preference. Moreover, these AA matrices are only partly predicted by nucleotide subs

SUBMITTER: Shauli T 

PROVIDER: S-EPMC8445205 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature