Local mutation rate drives tRNA gene evolution

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.

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Genome Size Reduction and Transposon Activity Impact tRNA Gene Diversity While Ensuring Translational Stability in Birds

Genome Biology and Evolution ◽

10.1093/gbe/evab016 ◽

2021 ◽

Vol 13 (4) ◽

Cited By ~ 1

Author(s):

Jente Ottenburghs ◽

Keyi Geng ◽

Alexander Suh ◽

Claudia Kutter

Keyword(s):

Trna Gene ◽

Gene Evolution ◽

Phenotypic Diversity ◽

Gene Diversity ◽

Phylogenetic Analyses ◽

Genetic Regulation ◽

Bird Species ◽

Protein Translation ◽

Trna Genes ◽

Avian Genomes

Abstract As a highly diverse vertebrate class, bird species have adapted to various ecological systems. How this phenotypic diversity can be explained genetically is intensively debated and is likely grounded in differences in the genome content. Larger and more complex genomes could allow for greater genetic regulation that results in more phenotypic variety. Surprisingly, avian genomes are much smaller compared to other vertebrates but contain as many protein-coding genes as other vertebrates. This supports the notion that the phenotypic diversity is largely determined by selection on non-coding gene sequences. Transfer RNAs (tRNAs) represent a group of non-coding genes. However, the characteristics of tRNA genes across bird genomes have remained largely unexplored. Here, we exhaustively investigated the evolution and functional consequences of these crucial translational regulators within bird species and across vertebrates. Our dense sampling of 55 avian genomes representing each bird order revealed an average of 169 tRNA genes with at least 31% being actively used. Unlike other vertebrates, avian tRNA genes are reduced in number and complexity but are still in line with vertebrate wobble pairing strategies and mutation-driven codon usage. Our detailed phylogenetic analyses further uncovered that new tRNA genes can emerge through multiplication by transposable elements. Together, this study provides the first comprehensive avian and cross-vertebrate tRNA gene analyses and demonstrates that tRNA gene evolution is flexible albeit constrained within functional boundaries of general mechanisms in protein translation.

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Transfer RNA genes experience exceptionally elevated mutation rates

10.1101/229906 ◽

2017 ◽

Cited By ~ 1

Author(s):

Bryan P. Thornlow ◽

Josh Hough ◽

Jacquelyn M. Roger ◽

Henry Gong ◽

Todd M. Lowe ◽

...

Keyword(s):

Mutation Rate ◽

Sequence Variation ◽

Trna Gene ◽

Purifying Selection ◽

Transfer Rna ◽

Mutation Rates ◽

Biological Synthesis ◽

Human Populations ◽

Trna Genes ◽

Mutational Load

AbstractTransfer 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 seven and ten 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 new method for estimating individual tRNA gene activity. Collectively, this study illuminates the extreme competing forces in tRNA gene evolution, and implies that mutations at tRNA loci contribute disproportionately to mutational load and have unexplored fitness consequences in human populations.Significance StatementWhile transcription-associated mutagenesis (TAM) has been demonstrated for protein coding genes, its implications in shaping genome structure at transfer RNA (tRNA) loci in metazoans have not been fully appreciated. We show that cytosolic tRNAs are a striking example of TAM because of their variable rates of transcription, well-defined boundaries and internal promoter sequences. tRNA loci have a mutation rate approximately seven-to tenfold greater than the genome-wide average, and these mutations are consistent with signatures of TAM. These observations indicate that tRNA loci are disproportionately large contributors to mutational load in the human genome. Furthermore, the correlations between tRNA locus variation and transcription implicate that prediction of tRNA gene expression based on sequence variation data is possible.

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Disrupted tRNA Genes and tRNA Fragments: A Perspective on tRNA Gene Evolution

Life ◽

10.3390/life5010321 ◽

2015 ◽

Vol 5 (1) ◽

pp. 321-331 ◽

Cited By ~ 14

Author(s):

Akio Kanai

Keyword(s):

Trna Gene ◽

Gene Evolution ◽

Trna Genes

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An evaluation of mitochondrial tRNA gene evolution and its relation to the genetic code

Canadian Journal of Biochemistry ◽

10.1139/o82-056 ◽

1982 ◽

Vol 60 (4) ◽

pp. 475-479 ◽

Cited By ~ 14

Author(s):

R. J. Cedergren

Keyword(s):

Genetic Code ◽

Trna Gene ◽

Gene Evolution ◽

Sequence Data ◽

Cellular Systems ◽

Trna Genes ◽

Gene Structures ◽

And Function ◽

First Time ◽

Mitochondrial Trna Gene

Extensive sequence data on mitochondrial (mt) tRNAs give for the first time an opportunity to evaluate tRNA gene evolution in this organelle. Deductions from these gene structures relate to the evolution of tRNA genes in other cellular systems and to the origin of the genetic code. Mt tRNAs, in contrast to the prokaryotic nature of chloroplastic tRNA structure, can not at the present time be definitely related to either prokaryotic or eukaryotic tRNAs, probably because of a higher mutation rate in mitochondria.Fungal mt tRNAs having the same anticodon and function are generally similar enough to be considered homologous. Comparisons of all mt tRNA sequences contained in the same mitochondrion indicate that some tRNAs originated by duplication of a prototypic gene which, after divergence, led to tRNAs having different amino acid specificities. The deviant mt genetic code, although admittedly permitting a simpler decoding mechanism, is not useful in determining whether the origin of mitochondria had preceded or was derived from prokaryotes or eukaryotes, since the genetic code is variable even among mitochondria. Variants of the mt genetic code lead to speculation on the nature of die primordial code and its relation to the present "universal" code.

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