X-Chromosome Inactivation in Marsupials

Abstract

Marsupial (metatherian) mammals resemble their eutherian ('placental') counterparts in having inacti- vation of one of the two X chromosomes in the soma and premeiotic germ cells of their females. The marsupial X-inactivation system differs from the eutherian system in two respects: firstly, inactivation occurs for the paternally derived allele, i.e. it is not random, and secondly it is often incomplete. Data are available for four X-linked loci, all controlling enzyme structure: glucose-6- phosphate dehydrogenase (G6PD), phosphoglycerate kinase 1 (PGKl), alpha-galactosidase (GLA) and hypoxanthine phosphoribosyl transferase (HPRT). Both the G6PD and PGKl loci exhibit incomplete X-chromosome inactivation. The pattern of partial expression differs from tissue to tissue and from species to species. One of the two X chromosomes exhibits late replication, even in cells where a paternally derived gene is partly active, showing that late replication and absence of transcription are not completely correlated. Sex chromatin bodies are not as easily found as in some eutherians. In marsupials they are most clearly demonstrable in species with small Y chromosomes. Investigations into X-inactivation in early development have just begun. Absence of inactivation at the G6PD locus in yolk sac of a kangaroo has been observed. All other tissues exhibited complete paternal X-inacti- vation for G6PD. In a dasyurid, GLA showed complete paternal X-inactivation in all embryonic and extra-embryonic tissues. The role, if any, of methylation of cytosine residues in CpG pairs in the maintenance of X-inactivation in marsupials is unclear. Preliminary evidence indicates that sex-specific differences in methylation of sex linked genes do exist in marsupials.