Incomplete transcriptional dosage compensation of vertebrate sex chromosomes is balanced by post-transcriptional compensation

Abstract

Heteromorphic sex chromosomes (XY or ZW) present problems of gene dosage imbalance between the sexes, and with the autosomes. Mammalian X chromosome inactivation was long thought to imply a critical need for dosage compensation in vertebrates. However, the universal importance of sex chromosome dosage compensation was questioned by mRNA abundance measurements that demonstrated sex chromosome transcripts are neither balanced between the sexes or with autosomes in monotreme mammals or birds. Here, we demonstrate unbalanced mRNA levels of X genes in platypus males and females that correlate with differential loading of histone modifications, and confirm that transcripts of Z genes are unbalanced between males and females also in chicken. However, we found that in both species, median male to female protein abundance ratios were 1:1, implying an additional level of post-transcriptional control. We conclude that parity of sex chromosome output is achieved in birds, as well as all mammal groups, by a combination of transcriptional and post-transcriptional control, consistent with an essential role for sex chromosome dosage compensation in vertebrates.

Functional coherence of theXistandRSXprotein interactomes: X chromosome inactivation in marsupials

“…Balancing of sex chromosome-borne gene expression between sexes in the proteome has also been identified in the more distantly related platypus ( Ornithorhynchus anatinus ) and chicken ( Gallus gallus ). This highlights the possibility of post-transcriptional regulation being an ancestral strategy for fine tuning expression of sex chromosome genes in both sexes ( 41 ).…”

Aggregation‐prone peptides from within a non‐self‐protein homoaggregate are preferred for MHC association: Historical overview

“…[62][63][64][65] This indicated the 'exquisite precision' of the fine-tuning of cytosolic protein concentrations, rather than mRNA concentrations. [66][67][68] Thus, noting that a failure to inhibit one X chromosome in females would increase aggregation pressure and perhaps explain increased susceptibility of females to autoimmune diseases, a hypothesis of aggregation-based self/non-selfdiscrimination emerged. 8,15 Consistent with recent work, 29,33 the hypothesis exploited knowledge that 'self' intracellular protein concentrations, with the aid of appropriate molecular chaperones (e.g.…”

“…Further guidance came from the need of the two sexes to sustain equal protein concentrations within cells (X‐chromosome dosage compensation) 62–65 . This indicated the ‘exquisite precision’ of the fine‐tuning of cytosolic protein concentrations, rather than mRNA concentrations 66–68 . Thus, noting that a failure to inhibit one X chromosome in females would increase aggregation pressure and perhaps explain increased susceptibility of females to autoimmune diseases, a hypothesis of aggregation‐based self/non‐self‐discrimination emerged 8,15 …”