Recent, full-length gene retrocopies are common in canids

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• Gene retrocopies, or retro copy number variants (retroCNVs), originate from processed mRNA and can insert into genomes.
• While many retrocopies are inactive, active LINE-1 sequences in mammals can generate new ones, often missed by standard sequencing analysis.
• Previous studies linked specific FGF4 retroCNVs to canine skeletal dysplasias, but a comprehensive analysis of canid retroCNVs was lacking.

Purpose of the Study:

• To characterize the landscape of retro copy number variants (retroCNVs) across diverse canid breeds using whole-genome sequencing.
• To identify parent genes and insertion sites of retroCNVs in canids.
• To compare retroCNV frequency between dogs and humans and explore potential functional implications.

Main Methods:

• Whole-genome sequencing data from 293 canids across 76 breeds were analyzed.
• RetroCNV parent genes were identified using mRNA-specific 30-mers.
• RetroCNV insertion sites were pinpointed through discordant read analysis.

Main Results:

• 1911 retroCNVs from 1179 parent genes were identified in canids, with 1236 identical to their parent genes.
• Dogs averaged 54.1 total retroCNVs and 1.4 private retroCNVs.
• Evidence of testicular expression was found for 12% of analyzed retroCNVs, and 97 retroCNVs showed significant F_ST across breeds, suggesting selection. Canine retroCNV frequency was 13-fold higher than in humans.

Conclusions:

• Retro copy number variants (retroCNVs) represent a substantial and largely unexplored source of genetic variation in canids.
• RetroCNVs contribute to genome plasticity and are important considerations for trait and disease investigations in dogs.
• The high frequency and potential selection of retroCNVs in dogs warrant further research into their functional impact.