Alternative splicing and environmental adaptation in wild house mice

Area of Science:

• Evolutionary genetics
• Molecular mechanisms of adaptation
• Gene regulation

Background:

• Adaptive evolution is driven by genetic and molecular changes.
• Gene regulation, particularly mRNA abundance, is a known contributor to adaptation.
• The role of post-transcriptional processing, like alternative splicing, in adaptation is less understood.

Purpose of the Study:

• To identify candidate genes for local adaptation in house mice using alternative splicing.
• To investigate the role of alternative splicing in environmental adaptation along a latitudinal gradient.
• To differentiate the adaptive roles of alternative splicing versus mRNA abundance changes.

Main Methods:

• Analysis of exome sequences and RNA-Seq data from wild house mice (Mus musculus domesticus).
• Identification of alternatively spliced transcripts with population-specific and clinal variation.
• Association studies to detect cis-acting splicing quantitative trait loci (cis-sQTL).
• Overlap analysis with targets of selection from genome scans.

Main Results:

• Identified alternatively spliced transcripts showing clinal variation across a latitudinal transect.
• Discovered cis-sQTL overlapping with known targets of selection.
• Found that many candidate genes are associated with body size, a clinally varying trait.
• Observed no overlap with genes previously identified through changes in mRNA abundance.

Conclusions:

• Alternative splicing represents a distinct molecular mechanism contributing to environmental adaptation in house mice.
• These findings highlight the importance of post-transcriptional regulation in evolutionary adaptation.
• Alternative splicing and changes in mRNA abundance may act as separate pathways for adaptive evolution.