Unravelling the evolutionary origins of X chromosome inactivation in mammals: insights from marsupials and monotremes

Abstract

Determining the evolutionary origin of X inactivation mechanisms in mammals requires knowledge of features of X inactivation across all three major mammal lineages; monotremes, marsupials and eutherians. In the past, research into X inactivation in marsupials and monotremes lagged far behind the major advances made in understanding the mechanisms of X inactivation in human and mouse. Fragmentary knowledge of the genic content and sequence of marsupial and monotreme X chromosomes has been alleviated by the recent release of genome sequences for two marsupials and one monotreme. This has lead to a number of important findings, among which is the absence of XIST in marsupials and monotremes, and the surprising finding that X-borne genes in platypus are subject to stochastic transcriptional inhibition rather than whole chromosome inactivation. Availability of sequence data, and new techniques for studying expression and chromatin modification, now make rapid advance possible.

The sex-specific region of sex chromosomes in animals and plants

“…Consistent with this hypothesis, XCI is limited to therian mammals with internal gestation and absent in egg-laying mammals, or monotremes (Deakin et al 2008). Furthermore, it is the paternal X that is inactivated in marsupials (Deakin et al 2009;Namekawa et al 2007). This is in contrast to most eutherians in which XCI randomly affects the maternal or paternal chromosome in the developing embryo.…”

“…Because X inactivation of the paternal X is limited primarily to marsupials, paternal imprinting of the X is considered the ancestral condition, which is maintained to a limited degree in mice, but is lost in most other eutherians (Deakin et al 2009;Namekawa et al 2007). However, genomic analyses of paternal XCI in the marsupial Monodelphis domestica (the South American opossum) and mice provide conflicting viewpoints on the evolutionary origins of paternal imprinting in mice.…”

“…In the opossum, transcriptionally repressed X-linked genes are reactivated in round spermatids to be subsequently silenced in the developing embryo, whereas in the mouse, imprinting of the paternal X is at least partially maintained and inherited by offspring (Mahadevaiah et al 2009). It may be that XCI has evolved along separate evolutionary trajectories in marsupials and eutherians (Deakin et al 2009). Indeed, though they share limited aspects of XCI (including, at least in some cell types, transcription-repressing histone modifications such as H3K27 trimethylation) the molecule that triggers XCI in eutherians, the non-coding RNA XIST, is noticeably lacking in marsupials (Chaumeil et al 2011;Davidow et al 2007;Hore et al 2007;Mahadevaiah et al 2009).…”

Kangaroo gene mapping and sequencing: insights into mammalian genome evolution

“…But while I was away, Des, with colleagues from Macquarie University, showed that the kangaroo X chromosome differs fundamentally from that of placental mammals in that it is always the paternal X that is inactivated, the first demonstration of imprinting in a mammal (Richardson et al 1971;Sharman 1971). Not only was the process in marsupials imprinted, but it was incomplete and tissue specific (Cooper et al 1993;Deakin et al 2009). …”

Mechanistic concepts in X inactivation underlying dosage compensation in mammals

“…Presently, it is thought that the mammalian Xist gene may have been derived from a protein-coding gene, Lnx3 (Duret et al, 2006), in a process that involved the insertion of transposable elements (Elisaphenko et al, 2008). Interestingly, the genomic region around the Xic shows different arrangements in placental mammals and marsupials and is autosomal in monotremes (reviewed in Deakin et al, 2009). The Xic region has undergone repeated genetic rearrangements during the evolution of mammals.…”