# Comprehensive Analysis of Rodent-Specific Probasin Gene Reveals Its Evolutionary Origin in Pseudoautosomal Region and Provides Novel Insights into Rodent Phylogeny

## TL;DR

This study traces the evolutionary origin of the probasin gene in rodents, revealing its unique presence in rodent species and how it evolved from a pseudoautosomal region to the X-chromosome.

## Contribution

The study identifies the evolutionary origin of the rodent-specific probasin gene and challenges current phylogenetic understanding of rodent tribes.

## Key findings

- Probasin originated in the pseudoautosomal region and later recombined to the X-chromosome in mouse-like rodents.
- Sequence variations in probasin challenge current phylogenetic relationships among rodent tribes.
- Probasin is conserved in mouse-like species but absent in non-rodent mammals like humans.

## Abstract

The house mouse, Mus musculus, is the preeminent rodent employed in basic biomedical research to understand the systemic functions of individual genes in vivo. Genes involved in human pathologies regularly find their counterparts in the mouse genome; however, little is known about genes exclusive to primates or rodents. In this study, we aimed at finding the evolutionary origin of the probasin gene, which is only described in mice and rats and is absent in humans. We traced its origin back to when ancestors of mouse-like rodents such as hamsters, mice, and moles separated, consequently becoming absent outside the mammal order of rodents. Probasin initially emerged as a gene present on both sex chromosomes in a specialized region that behaves like autosomes, hence termed pseudoautosomal. During the evolution of mouse-like rodents, it recombined to the X-specific region on the X-chromosome. Our study highlights this transition, suggesting that probasin has remained, at present, largely conserved in mouse-like species. Close analysis of sequence variations in the probasin gene cause us to challenge the current understanding about the phylogenetic relationship among some tribes within the family of mice.

Probasin protein was originally identified as a basic protein present in rat prostate epithelium. So far, its physiological role, its origin, and its presence in other species including humans remain largely elusive. With the ever-growing number of genome assemblies, thus far, probasin genes (Pbsn/PBSN) have only been predicted in a subset of rodent genomes. In this study, we addressed the phylogeny of probasin genes and found them to be exclusively present in members of the superfamily Muroidea. It first emerged in the so-called pseudoautosomal region, a subtelomeric gene cluster of both mammalian sex chromosomes. During evolution of the Muroidea lineages, probasin recombined to the X-specific region of the X-chromosome in mice and hamster species. This event likely saved the gene from events that other pseudoautosomal genes suffered, namely displaying an increase in G and C nucleotide composition or accumulation of repetitive elements. We observed changes to its coding region, e.g., sequence insertions in exon 6, which challenge the current understanding of rodent phylogeny, in particular regarding the evolutionary history of tribe formation within the subfamily Murinae. Analyzing the evolution of probasin genes in Muroidea allows fostering understanding of phylogenetic relationships in one of the largest groups of mammalian species.