ArticleMolecular biology and evolution2014
Conserved proteins are fragile.
Article in Molecular biology and evolution, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Gene function predicts divergence across molecular levels.bioRxiv : the preprint server for biology · 2026Article
- A Tale of Too Many Trees: A Conundrum for Phylogenetic Regression.Molecular biology and evolution · 2025Article
- Predicting evolutionary targets and parameters of gene deletion from expression data.Bioinformatics advances · 2024Article
- Predicting gene expression divergence between single-copy orthologs in two species.Genome biology and evolution · 2023Article
- Article
- Loss-of-function Mutations K11E or E271K Lead to Novel Tumor Suppression, Implicate Nucleolar Helicase DDX24 Oncogenicity.International journal of medical sciences · 2022Article
- Learning Retention Mechanisms and Evolutionary Parameters of Duplicate Genes from Their Expression Data.Molecular biology and evolution · 2021Article
- Lineage-Specific Expression Divergence in Grasses Is Associated with Male Reproduction, Host-Pathogen Defense, and Domestication.Genome biology and evolution · 2019Article
- Natural Selection Drives Rapid Functional Evolution of Young Drosophila Duplicate Genes.Molecular biology and evolution · 2017Article
- A benchmark of gene expression tissue-specificity metrics.Briefings in bioinformatics · 2017Article
- Article
- Universal distribution of mutational effects on protein stability, uncoupling of protein robustness from sequence evolution and distinct evolutionary modes of prokaryotic and eukaryotic proteins.Physical biology · 2015Article
- Genome-wide distribution comparative and composition analysis of the SSRs in Poaceae.BMC genetics · 2015Article
- Pleiotropy constrains the evolution of protein but not regulatory sequences in a transcription regulatory network influencing complex social behaviors.Frontiers in genetics · 2014Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Levels of selective constraint vary among proteins. Although strong constraint on a protein is often attributed to its functional importance, evolutionary rate may also be limited if a protein is fragile, such that a large proportion of amino acid replacements reduce its fitness. To determine the relative contributions of essentiality and fragility to selective constraint, we compared relationships of selection against nonsense mutations (snon) and selection against missense mutations (smis) to protein sequence conservation (Ka). As expected, snon is greater than smis; however, the correlation between smis and Ka is nearly three times stronger than the correlation between snon and Ka. Moreover, examination of relationships to gene expression level, tissue specificity, and number of protein-protein interactions shows that smis is more strongly correlated than snon to all three measures of biological function. Thus, our analysis reveals that slowly evolving proteins are under strong selective constraint primarily because they are fragile, and that this association likely exists because allowing a protein to function improperly, rather than removing it from a biological network, can negatively affect the functions of other molecules it interacts with and their downstream products.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.