Julie Perez

XY FEMALES DO BETTER THAN THE XX IN THE AFRICAN PYGMY MOUSE, MUS MINUTOIDES

All therian mammals have a similar XY/XX sex‐determination system except for a dozen species. The African pygmy mouse, Mus minutoides, harbors an unconventional system in which all males are XY, and there are three types of females: the usual XX but also XX* and X*Y ones (the asterisk designates a sex‐reversal mutation on the X chromosome). The long‐term evolution of such a system is a paradox, because X*Y females are expected to face high reproductive costs (e.g., meiotic disruption and loss of unviable YY embryos), which should prevent invasion and maintenance of a sex‐reversal mutation. Hence, mechanisms for compensating for the costs could have evolved in M. minutoides.

Insights into the evolutionary history of the X-linked sex reversal mutation in mus minutoides: clues from sequence analyses of the Y-linked Sry gene.

The African pygmy mouse, Mus minutoides, is one of the very few mammal species that deviates from the classical mammalian XX/XY sex chromosome system by presenting a high proportion of fully fertile sex-reversed females. Since the still unknown sex reversal mutation is X-linked (X*), they are designated as X*Y females. Until now, X*Y females had only been identified in Southern Africa, but data were lacking for the rest of the vast sub-Saharan distribution range of this species. In this study, the PCR genotyping of the Y-linked Sry gene on 72 females from Western Africa (Guinea, Ivory Coast and Ghana) uncovered 10 sex-reversed females distributed in the 3 countries. This expands our understanding of the geographical distribution and temporal origin (dated at 0.9 mya) of the sex reversal mutation. In addition, we sequenced and analyzed a fragment of the Sry gene (including the complete high-mobility group, i.e. HMG box, and the partial C-terminal region). The results demonstrate the presence of multiple polymorphic copies of the gene as reported in other rodent species and reveal, more unexpectedly, an extremely high proportion of amino acid replacement within the HMG box. In effect, the predicted HMG box protein sequence similarity between some populations of M. minutoides is as low as 94.9%, and at the interspecific level (within genus), it drops to only 91.1% between M. minutoides and M. musculus.

Space use variation in co-occurring sister species: response to environmental variation or competition?

Coexistence often involves niche differentiation either as the result of environmental divergence, or in response to competition. Disentangling the causes of such divergence requires that environmental variation across space is taken into account, which is rarely done in empirical studies. We address the role of environmental variation versus competition in coexistence between two rodent species: Rhabdomys bechuanae (bechuanae) and Rhabdomys dilectus dilectus (dilectus) comparing their habitat preference and home range (HR) size in areas with similar climates, where their distributions abut (allopatry) or overlap (sympatry). Using Outlying Mean Index analyses, we test whether habitat characteristics of the species deviate significantly from a random sample of available habitats. In allopatry, results suggest habitat selection: dilectus preferring grasslands with little bare soil while bechuanae occurring in open shrublands. In sympatry, shrubland type habitats dominate and differences are less marked, yet dilectus selects habitats with more cover than bechuanae. Interestingly, bechuanae shows larger HRs than dilectus, and both species display larger HRs in sympatry. Further, HR overlaps between species are lower than expected. We discuss our results in light of data on the phylogeography of the genus and propose that evolution in allopatry resulted in adaptation leading to different habitat preferences, even at their distribution margins, a divergence expected to facilitate coexistence. However, since sympatry occurs in sites where environmental characteristics do not allow complete species separation, competition may explain reduced inter-species overlap and character displacement in HR size. This study reveals that both environmental variation and competition may shape species coexistence.

Anatomical and Molecular Analyses of XY Ovaries from the African Pygmy Mouse Mus minutoides

The African pygmy mouse Mus minutoides is characterized by the presence of a high proportion of fertile XY females in natural populations. This species displays 2 morphologically different X chromosomes: the ancestral X and a shorter one designated as X*, feminizing the X*Y individuals. This strongly suggests that in the presence of an X* chromosome, the male differentiation program is not activated despite a functional Y chromosome. In this study, we compared the histology of the adult ovaries of the 3 female genotypes (XX, XX* and X*Y) and investigated the expression of some of the main genes involved in male and female differentiation. We found that X*Y gonads display a typical ovarian structure without any testicular organization. Moreover, the ovarian somatic marker FOXL2 is detected in X*Y follicle cells and exhibits the same pattern as in XX and XX* ovaries, whereas SOX9 and DMRT1 are absent at all stages of follicular differentiation. However, surprisingly, X*Y ovaries display a higher level of Sry transcripts compared to testes. Our findings confirm the complete sex reversal in X*Y individuals with no apparent sign of masculinization, providing an attractive model to unravel new gene interactions involved in the mammalian sex determination system.

New Insight into the Mechanism of Accumulation and Intraerythrocytic Compartmentation of Albitiazolium, a New Type of Antimalarial

ABSTRACT Bis-thiazolium salts constitute a new class of antihematozoan drugs that inhibit parasite phosphatidylcholine biosynthesis. They specifically accumulate in Plasmodium- and Babesia-infected red blood cells (IRBC). Here, we provide new insight into the choline analogue albitiazolium, which is currently being clinically tested against severe malaria. Concentration-dependent accumulation in P. falciparum-infected erythrocytes reached steady state after 90 to 120 min and was massive throughout the blood cycle, with cellular accumulation ratios of up to 1,000. This could not occur through a lysosomotropic effect, and the extent did not depend on the food vacuole pH, which was the case for the weak base chloroquine. Analysis of albitiazolium accumulation in P. falciparum IRBC revealed a high-affinity component that was restricted to mature stages and suppressed by pepstatin A treatment, and thus likely related to drug accumulation in the parasite food vacuole. Albitiazolium also accumulated in a second high-capacity component present throughout the blood cycle that was likely not related to the food vacuole and also observed with Babesia divergens-infected erythrocytes. Accumulation was strictly glucose dependent, drastically inhibited by H+/K+ and Na+ ionophores upon collapse of ionic gradients, and appeared to be energized by the proton-motive force across the erythrocyte plasma membrane, indicating the importance of transport steps for this permanently charged new type of antimalarial agent. This specific, massive, and irreversible accumulation allows albitiazolium to restrict its toxicity to hematozoa-infected erythrocytes. The intraparasitic compartmentation of albitiazolium corroborates a dual mechanism of action, which could make this new type of antimalarial agent resistant to parasite resistance.

Sex reversal induces size and performance differences among females of the African pygmy mouse, Mus minutoides

ABSTRACT Differences in biological performance, at both intra- and inter-specific levels, have often been linked to morphology but seldom to behavioural or genotypic effects. We tested performance at the intraspecific level by measuring bite force in the African pygmy mouse, Mus minutoides. This species displays an unusual sex determination system, with sex-reversed, X*Y females carrying a feminizing X* chromosome. X*Y females cannot be differentiated from XX females based on external or gonadal morphology; however, they are known to be more aggressive. We found that bite force was higher in X*Y females than in other females and males. We then performed geometric morphometric analyses on their skulls and mandibles and found that the higher performance of X*Y females was mainly explained by a greater overall skull size. The effects of the X* chromosome thus go beyond feminization, and extend to whole-organism performance and morphology. Our results also suggest limited effects of behaviour on bite force. Highlighted Article: Female Mus minutoides sometimes carry a Y chromosome. This chromosomal change is advantageous as sex-reversed females show greater skull size and higher bite force than XX females.

A Phylogeographic Survey of the Pygmy Mouse Mus minutoides in South Africa: Taxonomic and Karyotypic Inference from Cytochrome b Sequences of Museum Specimens

The African pygmy mice (Mus, subgenus Nannomys) are a group of small-sized rodents that occur widely throughout sub-Saharan Africa. Chromosomal diversity within this group is extensive and numerous studies have shown the karyotype to be a useful taxonomic marker. This is pertinent to Mus minutoides populations in South Africa where two different cytotypes (2n = 34, 2n = 18) and a modification of the sex determination system (due to the presence of a Y chromosome in some females) have been recorded. This chromosomal diversity is mirrored by mitochondrial DNA sequences that unambiguously discriminate among the various pygmy mouse species and, importantly, the different M. minutoides cytotypes. However, the geographic delimitation and taxonomy of pygmy mice populations in South Africa is poorly understood. To address this, tissue samples of M. minutoides were taken and analysed from specimens housed in six South African museum collections. Partial cytochrome b sequences (400 pb) were successfully amplified from 44% of the 154 samples processed. Two species were identified: M. indutus and M. minutoides. The sequences of the M. indutus samples provided two unexpected features: i) nuclear copies of the cytochrome b gene were detected in many specimens, and ii) the range of this species was found to extend considerably further south than is presently understood. The phylogenetic analysis of the M. minutoides samples revealed two well-supported clades: a Southern clade which included the two chromosomal groups previously identified in South Africa, and an Eastern clade that extended from Eastern Africa into South Africa. Congruent molecular phylogenetic and chromosomal datasets permitted the tentative chromosomal assignments of museum specimens within the different clades as well as the correction of misidentified museum specimens.

X inactivation in a mammal species with three sex chromosomes

X inactivation is a fundamental mechanism in eutherian mammals to restore a balance of X-linked gene products between XY males and XX females. However, it has never been extensively studied in a eutherian species with a sex determination system that deviates from the ubiquitous XX/XY. In this study, we explore the X inactivation process in the African pygmy mouse Mus minutoides, that harbours a polygenic sex determination with three sex chromosomes: Y, X, and a feminizing mutant X, named X*; females can thus be XX, XX*, or X*Y, and all males are XY. Using immunofluorescence, we investigated histone modification patterns between the two X chromosome types. We found that the X and X* chromosomes are randomly inactivated in XX* females, while no histone modifications were detected in X*Y females. Furthermore, in M. minutoides, X and X* chromosomes are fused to different autosomes, and we were able to show that the X inactivation never spreads into the autosomal segments. Evaluation of X inactivation by immunofluorescence is an excellent quantitative procedure, but it is only applicable when there is a structural difference between the two chromosomes that allows them to be distinguished.

Correction: Sex reversal induces size and performance differences among females of the African pygmy mouse,Mus minutoides(doi: 10.1242/jeb.157552)

There was an error published in J. Exp. Biol. (2017) 220 , [1947-1951][1] ([doi: 10.1242/jeb.157552][2]). The in vivo bite force values were overestimated as a result of incorrect settings of the piezoelectric force transducer used to measure bite forces; all bite force values are 2.4 times higher

Contents Vol. 8, 2014

Karin Schmid (address as for M. Schmid) E-mail: karin.schmid@uni-wuerzburg.de Peter Koopman Professor of Developmental Biology Institute for Molecular Bioscience The University of Queensland AU–Brisbane, Qld. 4072 (Australia) Tel. (+61) 7 3346 2059; Fax. (+61) 7 3346 2101 E-mail p.koopman@imb.uq.edu.au Manfred Schartl Institute of Physiological Chemistry I University of Würzburg Biozentrum, Am Hubland D–97074 Würzburg (Germany) Tel. (+49) 931 318 4148; Fax (+49) 931 318 4150 E-mail: phch1@biozentrum.uni-wuerzburg.de