Are Nonsynonymous Transversions Generally More Deleterious than Nonsynonymous Transitions?

Area of Science:

• Evolutionary biology
• Genomics
• Molecular evolution

Background:

• The genetic code's structure suggests nonsynonymous transitions are less harmful than transversions.
• Previous mutagenesis experiments yielded conflicting results on mutation deleteriousness.
• Laboratory fitness measures have limitations in sensitivity and natural mutation frequencies.

Purpose of the Study:

• To re-evaluate the relative deleteriousness of nonsynonymous transitions versus transversions using comparative genomics.
• To introduce and estimate a parameter (η) quantifying the ratio of fixation probabilities for these mutation types.

Main Methods:

• Extended the standard codon model of sequence evolution.
• Incorporated a parameter (η) for the fixation probability ratio of transitional to transversional nonsynonymous mutations.
• Estimated η from concatenated alignments of protein-coding DNA sequences in 90 species pairs.

Main Results:

• The ratio (η) varied significantly across species, ranging from 0.13 to 2.0.
• A notable number of species showed statistically significant deviations from the expected ratio (51 with η < 1, 30 with η > 1).
• Species-specific amino acid exchangeabilities were identified as the primary driver of the observed variation in η.

Conclusions:

• The relative deleteriousness of nonsynonymous transversions versus transitions is species-dependent.
• Genome-wide nucleotide substitution patterns in coding sequences exhibit significant species-specific variation.
• Evolutionary lineages display greater variability in substitution patterns than previously assumed.