Interspecific and Intragenic Differences in Codon Usage Bias Among Vertebrate Myosin Heavy-Chain Genes
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Synonymous codon usage bias is a broadly observed phenomenon in bacteria, plants, and invertebrates and may result from selection. However, the role of selective pressures in shaping codon bias is still controversial in vertebrates, particularly for mammals. The myosin heavy-chain (MyHC) gene family comprises multiple isoforms of the major force-producing contractile protein in cardiac and skeletal muscles. Slow and fast genes are tandemly arrayed on separate chromosomes, and have distinct patterns of functionality and expression in muscle. We analyze both full-length MyHC genes (~5400 bp) and a larger collection of partial sequences at the 3′ end (~500 bp). The MyHC isoforms are an interesting system in which to study codon usage bias because of their length, expression, and critical importance to organismal mobility. Codon bias and GC content differs among MyHC genes with regards to functional type, isoform, and position within the gene. Codon bias even varies by isoform within a species. We find evidence in favor of both chromosomal influences on nucleotide composition and selection against nonsense errors (SANE) acting on codon usage in MyHC genes. Intragenic variation in codon bias and elongation rate is significant, with a strong trend for increasing codon bias and elongation rate towards the 3′ end of the gene, although the trend is dependent upon the degeneracy class of the codons. Therefore, patterns of codon usage in MyHC genes are consistent with models supporting SANE as a major force shaping codon usage.
KeywordsMyosin heavy-chain Codon usage Muscle Translation selection Sequencing
Total GC content as fraction
Third position GC as fraction
Selection against nonsense errors
Relative codon bias score
Synonymous codon usage order
Harmonic mean of elongation rate
Observed expected cost of nonsense errors
Observed expected cost of translation
We are indebted to Adriana Briscoe for initially suggesting that we investigate codon bias in the myosin genes. Cyril-Jaimee Balangue provided many early contributions to sequence generation and analysis. Funding was provided by NIH Minority Biomedical Research Support of Competitive Research 2 S06 GM063119 and NIH MBRS RISE (BCR). MCA is supported by Mette Olufsen NSF/DMS-0616597.
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