Transcript diversity reflects deleterious RNA processing errors shaped by population size in metazoans.

In eukaryotes, alternative transcription initiation (ATI), alternative splicing (AS), and alternative polyadenylation (APA) result in multiple different transcripts per gene, but the biological significance of the transcript diversity produced remains controversial. Some suggested that this diversity is adaptive, while others contended that it is largely deleterious and arises from molecular errors in transcription and RNA processing. The error hypothesis makes a distinct prediction that is not expected under the adaptive hypothesis: transcript diversity declines with the effective population size (Ne) of the species because natural selection minimizing errors is more effective under larger Ne. By analyzing 166 transcriptomes from 75 metazoans, we report that transcript diversity measured by the percentage uses of minor ATI, AS, and APA sites decreases with Ne or its proxies. This observation supports the error hypothesis and suggests that metazoan transcript diversity is largely deleterious.