Comparative analysis of tRNAs across mouse strains reveals gene-specific conservation, divergence, and copy number variation.

backgroundTransfer RNAs (tRNAs) are essential for translation in all forms of life. tRNA genes in eukaryotes exist in multiple identical and non-identical copies across the genome to contribute to the tRNA repertoire of a cell. Given their central role in translation, tRNA genes are often assumed to be highly conserved across mammalian genomes. However, the true extent of tRNA gene conservation, divergence, and copy number variation has not been systematically explored. This study examines the evolution of tRNAs and tRNA-like elements (SINE elements, pseudo-tRNAs and other sequences similar to tRNAs) across closely related mouse strain genomes to understand how these loci diverge over short evolutionary timescales. By integrating previously published RNA Polymerase III Chromatin Immunoprecipitation followed by Sequencing (ChIP-Seq) data with a systematic identification of orthologous tRNA genes, we assess how actively transcribed tRNAs and tRNA-like elements vary between strains. We also compare the tRNA gene complement between strains to determine how the tRNA copy number changes.

resultsWe find that even actively transcribed tRNA genes can differ between closely related mouse strains, sometimes in ways that render them non-functional. While certain tRNAs exhibit rapid evolution and extensive sequence variation, others remain completely conserved. We also identify a subset of single-copy tRNAs that are remarkably conserved not only across mouse strains but even across mammals, suggesting specialized functions. Finally, our analysis infers large-scale gene conversion events among tRNAs and tRNA-like elements between mouse strains, offering new insight into the mechanisms shaping tRNA gene conservation and diversification.

conclusionsOur findings demonstrate that tRNA genes can be both gained and lost even among closely related mouse strains, revealing a dynamic and complex landscape of tRNA evolution. We observe a mixture of rapidly evolving and highly conserved tRNAs, reflecting distinct evolutionary pressures. Our results also show some evidence for the concerted evolution hypothesis, where multicopy tRNAs that can mutate are kept in sync through gene conversion. These findings not only illuminate the dynamics of tRNA gene evolution within a species but also provide a foundation for future efforts to experimentally modify tRNA loci in the genome by highlighting which tRNA genes are most likely to be functionally or evolutionarily significant.