Sequence shortening in the rodent ancestor

Area of Science:

• Genomics
• Evolutionary Biology
• Bioinformatics

Background:

• Insertions and deletions (indels) are key drivers of genomic evolution.
• A deletional bias (more deletions than insertions) is observed in many species, but not consistently in mammalian coding sequences.
• Previous studies yielded conflicting results on the extent and presence of deletional bias across mammalian lineages.

Purpose of the Study:

• To quantify the strength of deletional bias in mammalian genomes.
• To investigate the impact of mutation and selection on indel patterns.
• To compare indel dynamics in both coding and noncoding sequences across different mammalian lineages.

Main Methods:

• Quantification of indels in neutrally evolving noncoding and protein-coding sequences.
• Analysis across six mammalian evolutionary branches: human, macaque, ancestral primate, mouse, rat, and ancestral rodent.
• Utilized an improved algorithm (Prank(+F)) for accurate insertion placement in multiple sequence alignments.

Main Results:

• Contrary to prior findings, a strong deletional bias was identified only in the ancestral rodent branch.
• An estimated ~2.5% sequence loss in mammalian syntenic regions occurred in the ancestor of mice and rats due to this bias.
• Negative selection acts more intensely against amino acid-increasing mutations (insertions) than decreasing ones (deletions).

Conclusions:

• The rodent ancestral branch exhibits a significant deletional bias, contributing to substantial sequence loss.
• Selection pressures against indels are stronger in rodents than primates, correlating with effective population sizes.
• Differential selection on coding vs. noncoding sequences influences indel patterns and evolutionary trajectories.