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Gene Expression Intensity Shapes Evolutionary Rates of the Proteins Encoded by the Vertebrate Genome
Open accessAbstract
Natural selection leaves its footprints on protein-coding sequences by modulating their silent and replacement evolutionary rates. In highly expressed genes in invertebrates, these footprints are seen in the higher codon usage bias and lower synonymous divergence. In mammals, the highly expressed genes have a shorter gene length in the genome and the breadth of expression is known to constrain the rate of protein evolution. Here we have examined how the rates of evolution of proteins encoded by the vertebrate genomes are modulated by the amount (intensity) of gene expression. To understand how natural selection operates on proteins that appear to have arisen in earlier and later phases of animal evolution, we have contrasted patterns of mouse proteins that have homologs in invertebrate and protist genomes (Precambrian genes) with those that do not have such detectable homologs (vertebrate-specific genes). We find that the intensity of gene expression relates inversely to the rate of protein sequence evolution on a genomic scale. The most highly expressed genes actually show the lowest total number of substitutions per polypeptide, consistent with cumulative effects of purifying selection on individual amino acid replacements. Precambrian genes exhibit a more pronounced difference in protein evolutionary rates (up to three times) between the genes with high and low expression levels as compared to the vertebrate-specific genes, which appears to be due to the narrower breadth of expression of the vertebrate-specific genes. These results provide insights into the differential relationship and effect of the increasing complexity of animal body form on evolutionary rates of proteins.
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“It has been previously shown that highly expressed proteins evolve more slowly than proteins expressed at lower levels, i.e., they display a reduced protein divergence on the sequence level (Pal et al, 2001; Subramanian and Kumar, 2004)”
From The quantitative proteome of a human cell line (2011) · cites this paper as Subramanian and Kumar, 2004
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Ninova, M., Ronshaugen, M., & Griffiths‐Jones, S. (2014) · RNA · doi:10.1261/rna.041657.113 · Cited by 39
Metadata
- Authors
- Subramanian, S., & Kumar, S.
- Affiliations
- Arizona State University (US)
- Corresponding author
- Kumar, Sudhir
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-09-01
- Volume
- 168
- Issue
- 1
- Pages
- 373-381
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- OpenAlex
- W2104099887
- Cited by
- 250
- References
- 34
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 9 · 2023: 5 · 2022: 12 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 9 · 2017: 10 · 2016: 10 · 2015: 9 · 2014: 13 · 2013: 15 · 2012: 20
- FWCI
- 7.85
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Griffith Research Online (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- protein sequence evolution, evolutionary rates, purifying selection, synonymous divergence, codon usage bias, gene length, mouse protein, vertebrate evolution
- MeSH terms
- Animals, Drosophila melanogaster, Embryo, Mammalian, Embryo, Nonmammalian, Humans, Proteins, Genetic Variation, Gene Library, Gene Expression, Evolution, Molecular, Expressed Sequence Tags, Gene Expression Profiling, Takifugu, Mice
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