Open AccessContiguously hydrophobic sequences are functionally significant throughout the human exome
Author(s) -
Ruchi Lohia,
Matthew Hansen,
Grace Brannigan
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2116267119
Subject(s) - context (archaeology) , single nucleotide polymorphism , hydrophobic effect , snp , uncorrelated , exome , computational biology , genetics , biology , sequence (biology) , function (biology) , exome sequencing , mutation , gene , biochemistry , genotype , paleontology , statistics , mathematics
Significance Proteins rely on the hydrophobic effect to maintain structure and interactions with the environment. Surprisingly, natural selection on amino acid hydrophobicity has not been detected using modern genetic data. Analyses that treat each amino acid separately do not reveal significant results, which we confirm here. However, because the hydrophobic effect becomes more powerful as more hydrophobic molecules are introduced, we tested whether unbroken stretches of hydrophobic amino acids are under selection. Using genetic variant data from across the human genome, we find evidence that selection increases with the length of the unbroken hydrophobic sequence. These results could lead to improvements in a wide range of genomic tools as well as insights into protein-aggregation disease etiology and protein evolutionary history.