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Selective and Mutational Patterns Associated With Gene Expression in Humans
Abstract
We report the results of a comprehensive study of the influence of gene expression on synonymous codons, amino acid composition, and intron presence and size in human protein-coding genes. First, in addition to a strong effect of isochores, we have detected the influence of transcription-associated mutational biases (TAMB) on gene composition. Genes expressed in different tissues show diverse degrees of TAMB, with genes expressed in testis showing the greatest influence. Second, the study of tissues with no evidence of TAMB reveals a consistent set of optimal synonymous codons favored in highly expressed genes. This result exposes the consequences of natural selection on synonymous composition to increase efficiency of translation in the human lineage. Third, overall amino acid composition of proteins closely resembles tRNA abundance but there is no difference in amino acid composition in differentially expressed genes. Fourth, there is a negative relationship between expression and CDS length. Significantly, this is observed only among genes with introns, suggesting that the cause for this relationship in humans cannot be associated only with costs of amino acid biosynthesis. Fifth, we show that broadly and highly expressed genes have more, although shorter, introns. The selective advantage for having more introns in highly expressed genes is likely counterbalanced by containment of transcriptional costs and a minimum exon size for proper splicing.
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“…increasing G relative to C and T relative to A content synonymous codons increasing significantly with expres-of the coding strand (Sullivan 1995; Green et al. 2003). sion (the same two codons showing the strongest effectThen, we investigated consequences of TAMB by meaof expression in tissues…”
BackgroundResultTranslational selection and yeast proteome evolution
Akashi, H. (2003) · Genetics · doi:10.1093/genetics/164.4.1291 · Cited by 245
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Hearing silence: non-neutral evolution at synonymous sites in mammals
Chamary, J. V., Parmley, J. L., & Hurst, L. D. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1770 · Cited by 831
Determinants of translation efficiency and accuracy
Gingold, H., & Pilpel, Y. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.14 · Cited by 489
Modulated Expression of Specific tRNAs Drives Gene Expression and Cancer Progression
Goodarzi, H., Nguyen, H. C. B., Zhang, S., Dill, B. D., Molina, H., & Tavazoie, S. F. (2016) · Cell · doi:10.1016/j.cell.2016.05.046 · Cited by 462
Chamary, J., & Hurst, L. D. (2005) · Genome Biology · doi:10.1186/gb-2005-6-9-r75 · Cited by 332
A code within the genetic code: codon usage regulates co-translational protein folding
Liu, Y. (2020) · Cell Communication and Signaling · doi:10.1186/s12964-020-00642-6 · Cited by 252
Metadata
- Authors
- Comeron, J. M.
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-07-01
- Volume
- 167
- Issue
- 3
- Pages
- 1293-1304
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- OpenAlex
- W2037145016
- Cited by
- 200
- References
- 7
- FWCI
- 4.26
- Type
- journal article
- Language
- en
- Open access
- closed
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