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

## TL;DR

This study finds that transcript diversity in animals is mostly due to harmful RNA processing errors, not adaptive functions, and is reduced in species with larger population sizes.

## Contribution

The study provides empirical evidence that transcript diversity is shaped by population size and reflects deleterious RNA processing errors.

## Key findings

- Transcript diversity decreases with increasing effective population size (Ne) in metazoans.
- The percentage use of minor ATI, AS, and APA sites correlates negatively with Ne or its proxies.
- Findings support the error hypothesis over the adaptive hypothesis for transcript diversity.

## Abstract

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.

Alternative transcription initiation, splicing and polyadenylation generate
extensive transcript diversity in eukaryotes, but its evolutionary significance
has been disputed. This study analyses 166 transcriptomes across 75 metazoan
species to show that transcript diversity generally decreases with effective
population size, supporting the view that most transcript diversity reflects
deleterious RNA processing errors rather than adaptive functions.