# Asymmetry of nucleotide substitutions in tRNAs indicates common descent of modern organisms from a thermophilic ancestor

**Authors:** I.I. Titov

PMC · DOI: 10.18699/vjgb-25-116 · Vavilov Journal of Genetics and Breeding · 2025-12-01

## TL;DR

This paper suggests that modern organisms evolved from a thermophilic ancestor based on patterns of nucleotide substitutions in tRNA sequences.

## Contribution

The study identifies a universal directional bias in tRNA nucleotide substitutions, supporting a thermophilic LUCA.

## Key findings

- A universal vector of directed evolutionary change in tRNA sequences was discovered, favoring G→A and C→U substitutions.
- 16 out of 20 tRNA families show significant susceptibility to this change (p = 0.006).
- The pattern suggests a high GC content in the common ancestor, supporting a thermophilic LUCA.

## Abstract

The nature of the last universal common ancestor (LUCA) of all living organisms remains a controversial issue in biology. There is evidence of both thermophilic and mesophilic LUCA origin. The increasing complexity of the cellular apparatus during the evolution from early life forms to modern organisms could have manifested itself in long-term evolutionary changes in the nucleotide composition of genetic sequences. This work is devoted to the identification of such trends in tRNA sequences. The results of an evolutionary analysis of single-nucleotide substitutions in tRNAs of 123 species from three domains – Bacteria, Archaea and Eukaryota – are presented. A universal vector of directed evolutionary change in tRNA sequences has been discovered, in which substitutions of guanine (G) to adenine (A) and cytosine (C) to uracil (U) occur more frequently than the reverse. The most striking asymmetry in the number of substitutions is observed in the following transitions: a) purine-to-purine, where G→A outnumbers A→G, b) pyrimidine-to-pyrimidine, where C→U outnumbers U→C, and c) purine-to-pyrimidine and vice versa, where G→U outnumbers U→G. As a result, tRNAs could lose “strong” three-hydrogen-bond complementary pairs formed by guanine and cytosine and fix “weak” two-hydrogen-bond complementary pairs formed by adenine and uracil. 16 out of 20 tRNA families are susceptible to the detected change in sequence composition, which corresponds to the significance level p = 0.006 according to the one-sided binomial test. The identified pattern indicates a high GC content in the common ancestor of modern tRNAs, supporting the hypothesis that the last universal common ancestor (LUCA) lived in a hotter environment than do most contemporary organisms

## Linked entities

- **Species:** Bacteria (taxon 2), Archaea (taxon 2157), Eukaryota (taxon 2759)

## Full-text entities

- **Genes:** TRNG (tRNA-Gly) [NCBI Gene 4563] {aka MTTG}
- **Chemicals:** adenine (MESH:D000225), hydrogen (MESH:D006859), cytosine (MESH:D003596), guanine (MESH:D006147), uracil (MESH:D014498)
- **Mutations:** cytosine (C) to uracil (U), guanine (G) to adenine (A)

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12795830/full.md

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Source: https://tomesphere.com/paper/PMC12795830