Novel patterns of expression and recruitment of new genes on the t -haplotype, a mouse selfish chromosome

Abstract

The t -haplotype of mice is a classical model for autosomal transmission distortion. A largely non-recombining variant of the proximal region of chromosome 17, it is transmitted to more than 90% of the progeny of heterozygous males through the disabling of sperm carrying a standard chromosome. While extensive genetic and functional work has shed light on individual genes involved in drive, much less is known about the evolution and function of the rest of its hundreds of genes. Here, we characterize the sequence and expression of dozens of t -specific transcripts and of their chromosome 17 homologues. Many genes showed reduced expression of the t -allele, but an equal number of genes showed increased expression of their t -copy, consistent with increased activity or a newly evolved function. Genes on the t -haplotype had a significantly higher non-synonymous substitution rate than their homologues on the standard chromosome, with several genes harbouring dN/dS ratios above 1. Finally, the t -haplotype has acquired at least two genes from other chromosomes, which show high and tissue-specific expression. These results provide a first overview of the gene content of this selfish element, and support a more dynamic evolutionary scenario than expected of a large genomic region with almost no recombination.

Leveraging a natural murine meiotic drive to suppress invasive populations

“…These reference transcripts were derived from results of a recent study by Kelemen et al . (2022) 87 that analysed DNA and RNA sequences from a database of wild Mus samples 86 . This database includes whole-genome sequences from both +/ t and +/+ mice across all three M. musculus subspecies as well as a sister taxon ( M. spretus ).…”

“…This database includes whole-genome sequences from both +/ t and +/+ mice across all three M. musculus subspecies as well as a sister taxon ( M. spretus ). The original list (Supplementary Data 4 in Kelemen et al . (2022) 87 consists of 256 annotated contigs assembled from RNA-seq reads of +/ t mice, and subsequently filtered for those that had greater relative coverage of genomic reads mapped from +/ t compared to +/+ mice.…”

“…The original list (Supplementary Data 4 in Kelemen et al . (2022) 87 consists of 256 annotated contigs assembled from RNA-seq reads of +/ t mice, and subsequently filtered for those that had greater relative coverage of genomic reads mapped from +/ t compared to +/+ mice.…”

“…As it is generally not possible to extract haplotype information from pool-seq data, we used an approach wherein sequencing reads were mapped to a reference of diagnostic t-specific transcripts. These reference transcripts were derived from results of a recent study by Kelemen et al (2022) 86 that analysed DNA and RNA sequences from a database of wild Mus samples 85 . This database includes whole-genome sequences from both +/t and +/+ mice across all three M. musculus subspecies as well as a sister taxon (M. spretus).…”

“…In order to identify diagnostic t-specific transcripts for our study, we downloaded DNA sequence FASTQ files for +/t and +/+ mice from the Harr et al (2016) 86 database and re-mapped the forward reads of each sample to the transcripts using bowtie 2 88 . Following the procedure by Kelemen et al (2022) 87 , we then counted only reads that mapped perfectly to a transcript with no mismatches, and normalised these values by the total number of reads in each sequence dataset, multiplied by 1 x 10 6 to calculate reads per million (RPM). Diagnostic t-specific transcripts were then identified as those to which zero reads mapped from any +/+ individuals, and at least one read mapped in each +/t sample.…”