Relaxed sequence constraints favor mutational freedom in idiosyncratic metazoan mitochondrial tRNAs

Bernhard Kuhle,Joseph Chihade,Paul Schimmel

doi:10.1038/s41467-020-14725-y

Bernhard Kuhle, Joseph Chihade + Show 1 more

Open Access

https://doi.org/10.1038/s41467-020-14725-y

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Journal: Nature Communications	Publication Date: Feb 20, 2020
Citations: 16	License type: open-access

Affiliation: Scripps Research Institute, Carleton College

Abstract

Metazoan complexity and life-style depend on the bioenergetic potential of mitochondria. However, higher aerobic activity and genetic drift impose strong mutation pressure and risk of irreversible fitness decline in mitochondrial (mt)DNA-encoded genes. Bilaterian mitochondria-encoded tRNA genes, key players in mitochondrial activity, have accumulated mutations at significantly higher rates than their cytoplasmic counterparts, resulting in foreshortened and fragile structures. Here we show that fragility of mt tRNAs coincided with the evolution of bilaterian animals. We demonstrate that bilaterians compensated for this reduced structural complexity in mt tRNAs by sequence-independent induced-fit adaption to the cognate mitochondrial aminoacyl-tRNA synthetase (aaRS). Structural readout by nuclear-encoded aaRS partners relaxed the sequence constraints on mt tRNAs and facilitated accommodation of functionally disruptive mutational insults by cis-acting epistatic compensations. Our results thus suggest that mutational freedom in mt tRNA genes is an adaptation to increased mutation pressure that was associated with the evolution of animal complexity.

Highlights

Metazoan complexity and life-style depend on the bioenergetic potential of mitochondria
The analysis showed that mt tRNAs from both major bilaterian phyla, protostomes and deuterostomes, exhibit significantly increased sequence divergence and length variation compared with their cytoplasmic and non-bilaterian mitochondrial counterparts (Fig. 1a and Supplementary Fig. 1)
We considered the possibility that the idiosyncratic properties of mt aminoacyl-tRNA synthetase (aaRS)/tRNA systems that are common to bilaterian animals, might be a functional adaptation to specific requirements in bilaterians, in particular the need to deal with high sequence mutation rates in mitochondrially encoded tRNA genes

Summary

Introduction

Metazoan complexity and life-style depend on the bioenergetic potential of mitochondria. Throughout cellular life, aaRSdirected matching of tRNA anticodons with cognate amino acids in the aminoacylation reaction serves as a critical check-point for the fidelity of genetic code expression[16,17,18] This process critically depends on the aaRS’s ability to strictly discriminate cognate from non-cognate tRNAs. From prokaryotes to the eukaryote cytoplasm, tRNA recognition relies on two major factors: the canonical tRNA fold with its high structural and sequence complexity and thermodynamic stability, and a small fraction of nucleotides, termed identity and anti-identity elements, embedded into the canonical tRNA structural framework[17,19,20,21,22,23,24]. Exemplified by the unique loss of G3:U70 as identity element in the majority of bilaterian mt AlaRS/tRNAAla recognition systems, we suggest that coadaptation of nuclear-encoded synthetases to their mt tRNA partners altered the recognition rules to allow increased mutational freedom in mt tRNAs to mitigate mutational meltdown

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