Acquisition of ampliconic sequences marks a selfish mouse t-haplotype

Area of Science:

• Genetics
• Evolutionary Biology
• Genomics

Background:

• Mendelian genetics assumes equal allele transmission, but selfish genetic elements can bias inheritance.
• T-haplotypes in Mus musculus demonstrate extreme transmission bias, linked to inversions on chromosome 17.

Purpose of the Study:

• Investigate the evolution of transmission bias in large genomic regions.
• Understand the role of amplicons and inversions in the emergence of selfish chromosomes.

Main Methods:

• Generated a high-quality, single-haplotype assembly of a t-haplotype.
• Analyzed conserved amplicons across Mus species.
• Performed targeted deletion of a candidate selfish amplicon.

Main Results:

• Identified eight large amplicons with selfish alleles as a key feature of t-haplotypes.
• Found evidence that amplicons and inversions drove the origin of selfish chromosome 17 approximately 3 million years ago.
• Demonstrated that deleting a specific amplicon reduced transmission bias by ~3%.

Conclusions:

• Amplicon acquisition and large inversions are crucial in the evolution of selfish chromosomes.
• The evolution of t-haplotype amplicons parallels mammalian sex chromosome evolution.
• Selfish transmission drives evolutionary arms races and leaves genome-wide signatures.