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

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Genomics

Background:

• Eukaryotic genes generate diverse transcripts via alternative transcription initiation (ATI), alternative splicing (AS), and alternative polyadenylation (APA).
• The biological significance of this transcript diversity is debated, with hypotheses suggesting it is either adaptive or largely deleterious due to molecular errors.

Purpose of the Study:

• To investigate the role of effective population size (Ne) in shaping transcript diversity.
• To test the prediction that transcript diversity declines with increasing Ne, as predicted by the error hypothesis.

Main Methods:

• Analysis of 166 transcriptomes from 75 metazoan species.
• Quantification of transcript diversity using the percentage of minor ATI, AS, and APA sites.
• Correlation analysis between transcript diversity metrics and Ne or its proxies.

Main Results:

• Transcript diversity, measured by the usage of minor ATI, AS, and APA sites, significantly decreases with increasing effective population size (Ne).
• This inverse correlation was observed across a diverse range of metazoan species.

Conclusions:

• The findings support the error hypothesis, suggesting that transcript diversity is largely a byproduct of molecular errors in transcription and RNA processing.
• Natural selection is more effective at minimizing these errors in species with larger effective population sizes, leading to reduced transcript diversity.