The Status of Dosage Compensation in the Multiple X Chromosomes of the Platypus

Abstract

Dosage compensation has been thought to be a ubiquitous property of sex chromosomes that are represented differently in males and females. The expression of most X-borne genes is equalized between XX females and XY males in therian mammals (marsupials and “placentals”) by inactivating one X chromosome in female somatic cells. However, compensation seems not to be strictly required to equalize the expression of most Z-borne genes between ZZ male and ZW female birds. Whether dosage compensation operates in the third mammal lineage, the egg-laying monotremes, is of considerable interest, since the platypus has a complex sex chromosome system in which five X and five Y chromosomes share considerable genetic homology with the chicken ZW sex chromosome pair, but not with therian XY chromosomes. The assignment of genes to four platypus X chromosomes allowed us to examine X dosage compensation in this unique species. Quantitative PCR showed a range of compensation, but SNP analysis of several X-borne genes showed that both alleles are transcribed in a heterozygous female. Transcription of 14 BACs representing 19 X-borne genes was examined by RNA-FISH in female and male fibroblasts. An autosomal control gene was expressed from both alleles in nearly all nuclei, and four pseudoautosomal BACs were usually expressed from both alleles in male as well as female nuclei, showing that their Y loci are active. However, nine X-specific BACs were usually transcribed from only one allele. This suggests that while some genes on the platypus X are not dosage compensated, other genes do show some form of compensation via stochastic transcriptional inhibition, perhaps representing an ancestral system that evolved to be more tightly controlled in placental mammals such as human and mouse.

The origin and evolution of vertebrate sex chromosomes and dosage compensation

“…The percentage of cells with asynchronous replication was lower than that observed for the mouse X, suggesting partial DC. Consistent with this was RNA-in situ hybridization, which indicated that some X-specific genes were compensated by regulating the probability that they are either mono-or bi-allelically transcribed (Deakin et al, 2008). This is similar to the more recent observations in marsupials (Al Nadaf et al, 2010), although the sex chromosomes are not homologous.…”

Species-specific differences in X chromosome inactivation in mammals

“…They have a complex sex chromosome system; for example, the platypus has ten sex chromosomes, females have five pairs of Xs and males have five Xs and five Ys (Grutzner et al 2004). A previous study demonstrated that while some genes on the platypus X are not dosage compensated, other genes show some form of compensation via stochastic transcriptional repression (Deakin et al 2008). Therefore, monotremes may not have a mechanism for dosage compensation that is comparable with that of eutherians and marsupials.…”

Specific patterns of histone marks accompany X chromosome inactivation in a marsupial

“…In the egg-laying monotremes, basal mammals that diverged from therians 166 Mya, multiple X chromosomes have homology not to the human X, but to the chicken Z chromosome (Veyrunes et al 2008). Like the chicken Z (Itoh et al 2007), platypus X chromosomes do not undergo inactivation, although some form of partial dosage compensation operates (Deakin et al 2008).…”