Contiguously hydrophobic sequences are functionally significant throughout the human exome

Lohia, Ruchi, Hansen, Matthew EB, Brannigan, Grace (March 2022) Contiguously hydrophobic sequences are functionally significant throughout the human exome. Proceedings of the National Academy of Sciences of USA, 119 (12). e2116267119. ISSN 0027-8424

[img] PDF
Contiguously hydrophobic sequences are functionally significant throughout the human exome.pdf
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (1MB)
URL: https://www.ncbi.nlm.nih.gov/pubmed/35294280
DOI: 10.1073/pnas.2116267119

Abstract

SignificanceProteins 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.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > SNP
bioinformatics > computational biology
Investigative techniques and equipment > whole exome sequencing
Investigative techniques and equipment > assays > whole exome sequencing
CSHL Authors:
Communities: CSHL labs > Gillis Lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 22 March 2022
Date Deposited: 07 Apr 2022 14:26
Last Modified: 07 Apr 2022 14:26
PMCID: PMC8944643
URI: https://repository.cshl.edu/id/eprint/40571

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving