Dataset Information

Slow protein evolutionary rates are dictated by surface-core association.

ABSTRACT: Why do certain proteins evolve much slower than others? We compared not only rates per protein, but also rates per position within individual proteins. For ?90% of proteins, the distribution of positional rates exhibits three peaks: a peak of slow evolving residues, with average log(2)[normalized rate], log(2)?, of ca. -2, corresponding primarily to core residues; a peak of fast evolving residues (log(2)? ? 0.5) largely corresponding to surface residues; and a very fast peak (log(2)? ? 2) associated with disordered segments. However, a unique fraction of proteins that evolve very slowly exhibit not only a negligible fast peak, but also a peak with a log(2)? ? -4, rather than the standard core peak of -2. Thus, a "freeze" of a protein's surface seems to stop core evolution as well. We also observed a much higher fraction of substitutions in potentially interacting residues than expected by chance, including substitutions in pairs of contacting surface-core residues. Overall, the data suggest that accumulation of surface substitutions enables the acceptance of substitutions in core positions. The underlying reason for slow evolution might therefore be a highly constrained surface due to protein-protein interactions or the need to prevent misfolding or aggregation. If the surface is inaccessible to substitutions, so becomes the core, thus resulting in very slow overall rates.

SUBMITTER: Toth-Petroczy A

PROVIDER: S-EPMC3131374 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Slow protein evolutionary rates are dictated by surface-core association.

Tóth-Petróczy Agnes A Tawfik Dan S DS

Proceedings of the National Academy of Sciences of the United States of America 20110620 27

Why do certain proteins evolve much slower than others? We compared not only rates per protein, but also rates per position within individual proteins. For ∼90% of proteins, the distribution of positional rates exhibits three peaks: a peak of slow evolving residues, with average log(2)[normalized rate], log(2)μ, of ca. -2, corresponding primarily to core residues; a peak of fast evolving residues (log(2)μ ∼ 0.5) largely corresponding to surface residues; and a very fast peak (log(2)μ ∼ 2) associ ...[more]

PMID: 21690394

Similar Datasets

Project description:BACKGROUND:Protein kinase (PK) genes comprise the third largest superfamily that occupy approximately 2% of the human genome. They encode regulatory enzymes that control a vast variety of cellular processes through phosphorylation of their protein substrates. Expression of PK genes is subject to complex transcriptional regulation which is not fully understood. PRINCIPAL FINDINGS:Our comparative analysis demonstrates that genomic organization of regulatory PK genes differs from organization of other protein coding genes. PK genes occupy larger genomic loci, have longer introns, spacer regions, and encode larger proteins. The primary transcript length of PK genes, similar to other protein coding genes, inversely correlates with gene expression level and expression breadth, which is likely due to the necessity to reduce metabolic costs of transcription for abundant messages. On average, PK genes evolve slower than other protein coding genes. Breadth of PK expression negatively correlates with rate of non-synonymous substitutions in protein coding regions. This rate is lower for high expression and ubiquitous PKs, relative to low expression PKs, and correlates with divergence in untranslated regions. Conversely, rate of silent mutations is uniform in different PK groups, indicating that differing rates of non-synonymous substitutions reflect variations in selective pressure. Brain and testis employ a considerable number of tissue-specific PKs, indicating high complexity of phosphorylation-dependent regulatory network in these organs. There are considerable differences in genomic organization between PKs up-regulated in the testis and brain. PK genes up-regulated in the highly proliferative testicular tissue are fast evolving and small, with short introns and transcribed regions. In contrast, genes up-regulated in the minimally proliferative nervous tissue carry long introns, extended transcribed regions, and evolve slowly. CONCLUSIONS/SIGNIFICANCE:PK genomic architecture, the size of gene functional domains and evolutionary rates correlate with the pattern of gene expression. Structure and evolutionary divergence of tissue-specific PK genes is related to the proliferative activity of the tissue where these genes are predominantly expressed. Our data provide evidence that physiological requirements for transcription intensity, ubiquitous expression, and tissue-specific regulation shape gene structure and affect rates of evolution.

Dataset Information

Slow protein evolutionary rates are dictated by surface-core association.

Publications

Slow protein evolutionary rates are dictated by surface-core association.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets