1. Codon usage in rare disease genes shows evolution- and phenotype-driven codon bias fingerprints
- Author
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Mingyan Fang, Rachele Rossi, Cristina Flesia, Wenyan Li, Chao Nie, Chongyi Jiang, Cong Yu, and Alessandra Ferlini
- Subjects
Genetics ,Dmd gene ,media_common.quotation_subject ,Codon usage bias ,Nonsense ,Missense mutation ,Codon optimization ,Biology ,Gene ,Phenotype ,Gene evolution ,media_common - Abstract
We compared relative synonymous codon usage (RSCU) across 15 species in 29 non-disease-causing (NDC) and 31 disease-causing (DC) kidney, muscle and skingenes. RSCU shows tissue-specific, evolutionarily conserved, and disease-specific fingerprints. The majority of DC genes display a lower codon usage bias (CUB) and show a different RSCU hierarchical clustering. Peculiarly, the DMD gene does not show any extreme CUB and still uses all synonymous codons. By “mapping-on-codons” its 2828 pathogenic variations, we found that missense and nonsense variations occurrence is CUB-independent. We conclude that DC and NDC genes have a specific RSCU behavior, underlined by a clear evolutionary trend, and a recognizable phenotype-related fingerprint. We suggest that studying CUB in rare-disease genes is a new and promising model to help understand its implications in gene evolution, mutational events, variations interpretation, and codon optimization for gene therapies.
- Published
- 2020
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