Short-range template switching in great ape genomes explored using pair hidden Markov models

Area of Science:

• Genomics
• Evolutionary Biology
• Bioinformatics

Background:

• Complex genomic rearrangements often result from template switch errors during DNA replication.
• These errors are typically studied at large scales, but their role in smaller-scale mutation clusters is less understood.
• Existing methods for detecting these smaller-scale events lack statistical rigor.

Purpose of the Study:

• To develop and apply an improved statistical approach for detecting short-range template switches.
• To characterize the role of template switches in generating mutation clusters in hominid genomes.
• To investigate the genomic and evolutionary consequences of these smaller-scale rearrangements.

Main Methods:

• Utilized pair hidden Markov models for detecting short-range template switches.
• Employed evolutionary genomic simulations to derive robust statistical measures.
• Analyzed multi-way alignments of hominid genomes.

Main Results:

• Template switch events are widespread in the evolution of great ape genomes.
• These events provide a parsimonious explanation for numerous complex mutation clusters.
• Initial template switch loci exhibit atypical patterns of DNA secondary structure and bending.

Conclusions:

• Short-range template switches are a significant driver of genomic variation in hominids.
• The developed statistical methods offer improved computational detection of template switch mutations.
• The approach is adaptable for comparative genomics across different species and evolutionary scales.