Complex Structure of Lasiopodomys mandarinus vinogradovi Sex Chromosomes, Sex Determination, and Intraspecific Autosomal Polymorphism

Abstract

The mandarin vole, Lasiopodomys mandarinus, is one of the most intriguing species among mammals with non-XX/XY sex chromosome system. It combines polymorphism in diploid chromosome numbers, variation in the morphology of autosomes, heteromorphism of X chromosomes, and several sex chromosome systems the origin of which remains unexplained. Here we elucidate the sex determination system in Lasiopodomys mandarinus vinogradovi using extensive karyotyping, crossbreeding experiments, molecular cytogenetic methods, and single chromosome DNA sequencing. Among 205 karyotyped voles, one male and three female combinations of sex chromosomes were revealed. The chromosome segregation pattern and karyomorph-related reproductive performances suggested an aberrant sex determination with almost half of the females carrying neo-X/neo-Y combination. The comparative chromosome painting strongly supported this proposition and revealed the mandarin vole sex chromosome systems originated due to at least two de novo autosomal translocations onto the ancestral X chromosome. The polymorphism in autosome 2 was not related to sex chromosome variability and was proved to result from pericentric inversions. Sequencing of microdissection derived of sex chromosomes allowed the determination of the coordinates for syntenic regions but did not reveal any Y-specific sequences. Several possible sex determination mechanisms as well as interpopulation karyological differences are discussed.

Unusual Mammalian Sex Determination Systems: A Cabinet of Curiosities

“…At first, the hypothesis of a Y-loss in L. mandarinus seems in total contradiction with the description of males with heterogametic sex chromosomes. However, chromosome painting analyses revealed that the sex chromosomes have fused with autosomes [84], and segregation studies show that one chromosome segregates as expected from a Y [85]. Whether this chromosome consists of the association of the ancestral Y (whole or fragmented) and a neo-Y, or is just composed of a neo-Y (following complete loss of the ancestral Y) remains to be determined.…”

“…For simplicity, we will refer to this chromosome as the "Y" thereafter. Based on crossbreeding experiments, Romanenko et al studied the transmission patterns of sex and neo-sex chromosomes and revised the sex-determining system of the mandarin vole: they describe one type of males (heterogametic), and three distinct female "karyomorphs": a homogametic one, a heterogametic one with the two morphologically different Xs, and a heterogametic one with the female specific X and the Y [85]. As mentioned by the authors, the pattern of association between phenotypic sex and sex chromosome combinations is highly reminiscent of the ones found in other rodents with X*Y females, and the change in sex determination of the mandarin vole fits well with the existence of an X-linked feminizing mutation.…”

“…However, the failure to detect any Y-specific genes or regions may suggest that this system has gone an evolutionary step further, with the loss of the ancestral Y after it became bisexually transmitted. Finally, Romanenko et al also noticed that the proportion of each genotype sired by females was inconsistent with a standard Mendelian inheritance of sex chromosome [85]. Roy reanalyzed this data and suggested that it could be explained by the presence of a male Y-drive in crosses with XX females, and male X-drive in crosses with XY females [86], which would make this drive system identical to the conditional drive described in the African pygmy mouse.…”

Multiple Sex Chromosome Drivers in a Mammal with Three Sex Chromosomes

“…Among those, there are species in which fertile XY females live alongside the standard XX females and XY male. Naturally occurring XY sex-reversal has evolved at least five times independently: twice in lemmings, in the wood and collared lemmings Myopus schisticolor and Dicrostonyx torquatus (5, 6), in several species of South American field mice of the genus Akodon (7, 8), in the African pygmy mouse Mus minutoides (9), and in the Mandarin vole Lasiopodomys mandarinus (10, 11). In all these rodents, sex-reversal is due to a feminizing mutation on the X, rather than a loss of function of the Y.…”

The Plasticity of Genome Architecture

“…As for sex chromosome evolution in mammals, Romanenko and collaborators [27] present the intriguing case of the mandarin vole (Lasiopodomys mandarinus), characterized by a complex sex chromosome system (neo-Xs). In their study, the authors provide a comprehensive view of this species combining conventional and molecular cytogenetic methods, single chromosome DNA sequencing, and breeding experiments, revealing the chromosome segregation pattern as well as the reproductive performance of different karyomorphs.…”