Transcriptomics

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Mammalian splicing divergence is shaped by drift, buffering in trans, and a scaling law


ABSTRACT: We investigated the cis-regulatory divergences in alternative splicing and their relationship with tissue-dependent trans-regulation in multiple tissues of an F1 hybrid mouse. By obtaining more than 240 million read pairs on average in each sample from 5 organs and ESC as well as published data in liver, we comprehensively analyzed the allelic splicing patterns across tissues in hybrid mice. We find that tissue-dependent regulation causing large splicing differences is highly conserved and likely functional, while splicing divergence mainly affects genes under relaxed selective constraints. Although cis-divergence is in general associated with higher densities of sequence variants in regulatory regions, events with high usage of the dominant isoform could tolerate more mutations, which explains the paradoxical sequence conservation pattern in their exonic versus intronic splicing site flanking regions. Finally, we demonstrated that non-adaptive mutations are often masked in tissues where accurate splicing likely is more important, and experimentally attributed such buffering effect to trans-regulatory splicing efficiency.

ORGANISM(S): Mus musculus Mus spretus

PROVIDER: GSE154727 | GEO | 2021/10/07

REPOSITORIES: GEO

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