The question of natural selection against mutable-to-terminator codons.

Area of Science:

• Molecular Biology
• Genetics
• Evolutionary Biology

Background:

• Codons differing by one base from a stop codon are hypothesized to be rare due to natural selection against harmful mutations.
• Previous assumptions suggested these 'mutable-to-terminator' codons face direct negative selection.

Purpose of the Study:

• To investigate the frequency of human codons with a single base difference from terminator triplets.
• To determine if natural selection directly reduces the frequency of these codons based on mutation risk.

Main Methods:

• Analysis of codon frequencies in human genes.
• Comparison of frequencies between codons mutable to terminators and similar codons not mutable to terminators.
• Examination of the relationship between codon ending (A, G, C, or T) and frequency.

Main Results:

• Codons mutable to terminators are infrequent in human genes.
• This infrequency is primarily due to their A or G ending, not their specific mutation risk to a terminator.
• Comparable codons ending in A or G that are not mutable to terminators are also infrequent.

Conclusions:

• Natural selection does not appear to directly eliminate individual codons mutable to terminators.
• The reduced frequency of these codons may be an indirect consequence of selection acting on mutation rates, favoring populations where purine-ending codons, including mutable-to-terminator ones, are generally less common.