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Nucleotide sequence divergence and functional constraint in mRNA evolution

T Miyata, T Yasunaga, T Nishida

    Proceedings of the National Academy of Sciences of the United States of America
    |December 1, 1980
    PubMed
    Summary
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    Synonymous codon substitutions evolve much faster than amino acid changes, offering a constant evolutionary rate suitable for a molecular clock. Noncoding regions show variable conservation, with some highly conserved and others diverging significantly.

    Area of Science:

    • Molecular Evolution
    • Genomics
    • Bioinformatics

    Background:

    • Understanding gene evolution requires analyzing nucleotide and amino acid substitution rates.
    • Previous studies have indicated varying evolutionary rates across different genomic regions.

    Purpose of the Study:

    • To compare substitution rates between synonymous codons and amino acids across various genes.
    • To estimate the evolutionary rate of synonymous substitution and assess its constancy.
    • To evaluate the potential of synonymous substitution rates for use as a molecular clock.

    Main Methods:

    • Comparative analysis of approximately 50 pairs of homologous nucleotide sequences for different genes.
    • Comparison of five pairs of messenger RNA (mRNA) sequences from species with similar divergence times.

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  • Estimation of evolutionary rates based on sequence divergence.

    • Main Results:

    • Synonymous codon substitutions occur at significantly higher rates than amino acid substitutions.
    • The average evolutionary rate of synonymous substitution is approximately 5.1 x 10^-9 per site per year and is relatively constant across different genes.
    • Noncoding regions exhibit differential evolutionary rates: intervening sequences and the 5' part of the 3' noncoding region diverge considerably, while the 5' noncoding region and the 3' part of the 3' noncoding region are highly conserved.

    Conclusions:

    • The constant evolutionary rate of synonymous substitution supports its utility as a molecular clock for phylogenetic analysis, particularly for duplicated genes.
    • Differential conservation in noncoding regions suggests functional constraints, with conserved regions likely involved in mRNA transcription and modification.