TAA optimality is supported both by enrichment in highly expressed genes and trends associated with effective population size. Supportive of gBGC, we observe (i) TGA usage trends are consistent at the focal stop codon and elsewhere (in UTR sequences) (ii) that higher TGA usage and higher TAA→TGA substitution rates are predicted by a high recombination rate and (iii) across species the difference in TAA TGA substitution rates between GC-rich and GC-poor genes is largest in genomes that possess higher between-gene GC variation.

We show that this mammalian exceptionalism is well explained by gBGC mimicking purifying selection and that TAA is the selectively optimal codon. Although in most taxa TAA is the optimal stop codon, TGA is both abundant and conserved in mammalian genomes. We propose that mammalian stop codon evolution provides a robust test case. As mutation is GC→AT biased, to demonstrate that gBGC does indeed cause false signals requires evidence that an AT-rich residue is selectively optimal compared to its more GC-rich allele, while showing also that the GC-rich alternative is conserved.

GC-biased gene conversion (gBGC), a meiotic mismatch repair bias strongly favouring GC over AT, can in principle mimic the action of selection, this being thought to be especially important in mammals. The assumption that conservation of sequence implies the action of purifying selection is central to diverse methodologies to infer functional importance.

Stop tagr