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Updated: Sep 17, 2025

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Macroevolutionary changes in natural selection on codon usage reflect evolution of the tRNA pool across a budding
Alexander L Cope1,2,3, Premal Shah1,3
1Department of Genetics, Rutgers University, Piscataway, NJ 08854.
Summary
Codon usage bias (CUB) varies across species due to microevolutionary forces. This study links changes in tRNA gene copy number and modifications to natural selection driving CUB in budding yeasts.
Area of Science:
- Evolutionary Biology
- Genomics
- Molecular Biology
Background:
- Synonymous codons are used unequally within genomes, a phenomenon known as codon usage bias (CUB).
- CUB varies significantly across species and reflects a balance between adaptive and nonadaptive microevolutionary processes.
- Understanding the link between CUB and molecular/biophysical processes is crucial for deciphering evolutionary mechanisms.
Purpose of the Study:
- To quantify natural selection and mutation biases on a per-codon basis in Saccharomycotina budding yeasts.
- To investigate how microevolutionary processes shape codon usage bias across species.
- To establish the link between microevolutionary changes and molecular mechanisms influencing CUB.
Main Methods:
- Employed a population genetics model to analyze codon usage bias.
- Quantified natural selection and mutation biases per codon.
- Examined the evolution of tRNA gene copy number (tGCN) and tRNA modification expression.
Main Results:
- Significant variation in natural selection and mutation biases was observed even between closely related yeasts.
- Across-species variation in natural selection correlated with the evolution of tRNA gene copy number (tGCN).
- Changes in tRNA modification expression also influenced natural selection on codon usage, independent of tGCN.
- Changes in tGCN often reflected alterations in genome-wide GC content, indicating a link to mutation biases.
Conclusions:
- The evolution of the tRNA pool, through changes in tGCN and tRNA modifications, directly impacts natural selection on codon usage.
- Changes in translation efficiency, driven by the tRNA pool, are a key mechanism linking microevolutionary processes to CUB.
- Alterations in microevolutionary processes, including mutation biases reflected in GC content, shape molecular mechanisms and ultimately influence macroevolutionary trait variation.
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