Rodents with No Y Chromosome and No Sry Gene

In mammalian species sex is determined by the X and Y chromosomes. Individuals with two X chromosomes (XX) become female, and those with one X chromosome and one Y chromosome (XY) will be male. This occurs because the Y chromosome carries an Sry gene, which is a transcription factor and triggers the developmental pathway for testis formation. In the absence of the Sry gene, the developmental pathway for ovary formation is chosen as a default option.

Fig. 1. Evolution of sex chromosomes, SRY, and CBX2 in the genus Tokudaia. a Evolutionary events inferred from the present study (red) and previous studies (black) are shown in the phylogeny, together with the geographical distribution of Tokudaia species. Ma: million years ago. b Adult female of Okinawa spiny rat.  c Sub-adult male (2).



Fig. 2. Karyotypes of Amami and Tokunoshima spiny rats (3).

However, there are exceptional species in rodents. Two species of the genus Tokudaia living in small islands called Amami Oshima (T. osimensis) and Tokunoshima (T. tokunoshimensis) near Okinawa, Japan, have neither the Y chromosome nor the Sry gene (Fig. 1). Furthermore, both males and females of these species have only one X chromosome, so that their sex chromosome type is XO in both sexes. In addition, the number of autosomal chromosomes is different between the two species. T. osimensis (Amami spiny rat) has 24 autosomal chromosomes, whereas T. tokunoshimensis (Tokunoshima spiny rat) has 44 autosomal chromosomes (Fig. 2). The genus Tokudaia have three species, and the remaining one (T. muenninki) lives in Okinawa Island. This Okinawa spiny rat has the normal sex chromosome type XX/XY, and the number of autosomal chromosomes is 42.

Molecular phylogenetic analysis has suggested that Okinawa spiny rats diverged from the other two Tokudaia species about 2.5 million years ago and Amami and Tokunoshima spiny rats diverged about one million years ago. Therefore, the chromosome number has changed rapidly in these species by means of fusion, fission, inversion, deletion, translocation, etc. In fact, there is evidence that the chromosomes of Okinawa spiny rat have also experienced structural changes frequently. However, these chromosomal changes are not surprising because chromosomes can change quite often in small populations.

The surprising finding here is that the Sry gene has been lost and the male and the female are determined by the male and the female X chromosomes, respectively. Therefore, the gene contents of the male and the female X chromosomes must be different. In a recent paper Kuroiwa et al. (1) studied this problem by examining the copy number and chromosomal location of 10 genes (Artx, Cbx2, Dmrt1, Fgf9, NroB1, Nr5A1, Rspo1, Sox9, Wnt4, Wnt1) that are concerned with the differentiation of gonads into testis or ovary. The reason why they studied these genes is that duplicates of these genes are often used as signal proteins for sex determination in other organisms such as birds, frogs, and medaka fish. They then found that there are multiple copies of Cbx2 genes in the Tokudaia species and that there are two or more copies of Cbx2 genes in males than in females in both Amami and Tokunoshima spiny rats. Because the Cbx2 gene is known to repress ovarian development in mice and humans, they concluded that a larger number of Cbx2 genes in males is probably responsible for testis development. However, this hypothesis has not been confirmed by isolating and characterizing the Cbx2 genes.

There are two more rodent species which have the XO/XO sex chromosome type in both males and females. They are mole voles (4), and their effective population size again appears to be small. At present, the evolutionary change of the sex determination system in mammals is believed to be rare, but this may not be the case if we examine the sex chromosomes in species of small population size.

In reptiles, amphibians, and fish the sex determination system is known to change rapidly in the evolutionary process. Particularly in reptiles, there are the genetic sex determination (GSD) including both the XY and ZW systems and the temperature dependent sex determination (TSD), and these systems are interchangeable in the evolutionary process (5). It is also known that one species of frog, Rana rugosa, contains geographical races with the XY and ZW systems, and the XY ↔ ZW change appears to have occurred recently by an inversion event in the sex chromosomes (6).

In vertebrates Dmrt genes are believed to be responsible for imitating the developmental pathway for the formation of male and female phenotypes, but various signal proteins that trigger the function of Dmrt genes are used in different species (7). Dmrt-triggering genes are apparently subject to a rapid evolutionary change. How this evolutionary change occurs is not well understood. 

References

1. Kuroiwa A, Handa S, Nishiyama C, Chiba E, Yamada F, Abe S, and Matsuda Y. 2011. Additional copies of CBX2 in the genomes of males of mammals lacking SRY, the Amami spiny rat (Tokudaia osimensis) and the Tokunoshima spiny rat (Tokudaia tokunoshimensis).Chromosome Res 19:635-644.

2. Murata C, Yamada F, Kawauchi N, Matsuda Y, and Kuroiwa A. 2012. The Y chromosome of the Okinawa spiny rat, Tokudaia muenninki, was rescued through fusion with an autosome. Chromosome Res 20:111-125.

3. Sutou S, Mitsui Y, and Tsuchiya K. 2001. Sex determination without the Y chromosome in two Japanese rodents Tokudaia osimensis osimensis and Tokudaia osimensis spp. Mamm Genome 12:17-21.

4. Bagheri-Fam S, Sreenivasan R, Bernard P, Knower KC, Sekido R et al. 2012. Sox9 gene regulation and the loss of the XY/XX sex-determining mechanism in the mole vole Ellobius lutescens. Chromosome Res 20:191-199.

5. Sarre SD, Ezaz T, and Georges A. 2011. Transitions between sex-determining systems in reptiles and amphibians. Annu Rev Genomics Hum Genet 12:391-406.

6. Miura I, Ohtani H, and Ogata M. 2012. Independent degeneration of W and Y sex chromosomes in frog Rana rugosa. Chromosome Res 20:47-55.

7. Kopp A. 2012. Dmrt genes in the development and evolution of sexual dimorphism. Trends Genet 28:175-184.