X-inactivation in marsupials and monotremes

Abstract

Marsupials (metatherian) and eutherians ('placental') are the two extant groups of live bearing mammals which constitute the Theria, as opposed to the Protheria, or egg-laying monotremes. The current estimates for times of separation are 145 MYR BP for Theria-Prototheria and 130 MYR for marsupial-eutherian. This review focuses mainly upon marsupial X-inactivation, the study of which has revealed differences between marsupials and eutherians in mechanisms of X-inactivation, and in the function of the system in dosage compensation and reproduction. Marsupials resemble eutherians in having inactivation of one of the two X chromosomes in the soma and pre-meiotic germ cells of their females. However, marsupial X-inactivation differs from its eutherian counterpart in two respects: firstly, the paternally derived allele is inactivated, and secondly it is sometimes incomplete. These differences exist despite the fact that the marsupial X is homologous to the human Xq. Data are available for five X-linked loci, four controlling enzyme structure: glucose-6-phosphate dehydrogenase (G6PD), phosphoglycerate kinase 1 (PGK1), alpha-galactosidase (GLA) and hypoxanthine phosphoribosyl transferase (HPRT) and for ribosomal RNA. Both the G6PD and PGK1 loci exhibit partial expression of the paternally derived allele, but the pattern of expression for the two loci differs between tissues and between species. The ribosomal RNA gene clusters are on the X of kangaroos and didelphids, and clusters from both chromosomes are expressed in females. One of the two X chromosomes exhibits late replication, in particular in cells where a paternally derived gene is partly active, demonstrating that late replication and absence of transcription are not necessarily correlated. Female specific sex chromatin bodies are most clearly defined in species with small Y chromosomes. The extra-embryonic (placental) membranes of marsupials also have patterns of inactivation which show species and locus differences. The paternally derived allele at the G6PD locus in yolk sac placenta of a kangaroo was not inactivated but was completely inactivated in all other embryonic tissues. In contrast, in a dasyurid (Australian carnivorous) marsupial, GLA showed complete paternal X-inactivation in all embryonic and extra-embryonic tissues. Although the Y is testis determining in marsupials, it appears that possession of a scrotum or pouch is under X chromosome control; XXY animals are pouched males and XO and XX/XO animals are females with scrota. Whether this is due to a dosage difference or whether it is an imprinting phenomenon remains to be decided. While sex specific differences in methylation of CpG residues have been found in the body of the gene, their role in marsupial X-inactivation is debatable.Monotremes sex chromosomes are difficult to study. The differentiation into X and Y seems to be incomplete. DNA replication studies indicate the possibility of X-inactivation, but demonstration of the phenomenon at the single gene level has not been possible.