Amino acid composition of proteins reduces deleterious impact of mutations

By Sahand Hormoz. 2013

71 citations recorded by the source corpus.

The evolutionary origin of amino acid occurrence frequencies in proteins (composition) is not yet fully understood. We suggest that protein composition works alongside the genetic code to minimize impact of mutations on protein structure. First, we propose a novel method for estimating thermodynamic stability of proteins whose sequence is constrained to a fixed composition. Second, we quantify the average deleterious impact of substituting one amino acid with another. Natural proteome compositions are special in at least two ways: 1) Natural compositions do not generate more stable proteins than the average random composition, however, they result in proteins that are less susceptible to damage from mutations. 2) Natural proteome compositions that result in more stable proteins (i.e. those of thermophiles) are also tuned to have a higher tolerance for mutations. This is consistent with the observation that environmental factors selecting for more stable proteins also enhance the deleterious impact of mutations.

Subfields: Genetics, Molecular Biology, Computational Biology & Bioinformatics

Citations in the corpus

• Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization (2015, unknown): “Indeed, hnRNPA1 is enriched in the aromatic residues phenylalanine and tyrosine and the positively charged residue arginine relative to the overall eukaryotic proteome (Hormoz, 2013).”