Transfer RNA genes experience exceptionally elevated mutation rates.
Proc Natl Acad Sci U S A
; 115(36): 8996-9001, 2018 09 04.
Article
em En
| MEDLINE
| ID: mdl-30127029
ABSTRACT
Transfer RNAs (tRNAs) are a central component for the biological synthesis of proteins, and they are among the most highly conserved and frequently transcribed genes in all living things. Despite their clear significance for fundamental cellular processes, the forces governing tRNA evolution are poorly understood. We present evidence that transcription-associated mutagenesis and strong purifying selection are key determinants of patterns of sequence variation within and surrounding tRNA genes in humans and diverse model organisms. Remarkably, the mutation rate at broadly expressed cytosolic tRNA loci is likely between 7 and 10 times greater than the nuclear genome average. Furthermore, evolutionary analyses provide strong evidence that tRNA genes, but not their flanking sequences, experience strong purifying selection acting against this elevated mutation rate. We also find a strong correlation between tRNA expression levels and the mutation rates in their immediate flanking regions, suggesting a simple method for estimating individual tRNA gene activity. Collectively, this study illuminates the extreme competing forces in tRNA gene evolution and indicates that mutations at tRNA loci contribute disproportionately to mutational load and have unexplored fitness consequences in human populations.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA de Transferência
/
Genes de Plantas
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Genes de Helmintos
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Arabidopsis
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RNA de Plantas
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RNA de Helmintos
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Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2018
Tipo de documento:
Article