The W, X, Y and Z of sex-chromosome dosage compensation

Abstract

In species with highly differentiated sex chromosomes, imbalances in gene dosage between the sexes can affect overall organismal fitness. Regulatory mechanisms were discovered in several unrelated animals, which counter gene-dose differences between females and males, and these early findings suggested that dosage-compensating mechanisms were required for sex-chromosome evolution. However, recent reports in birds and moths contradict this view because these animals locally compensate only a few genes on the sex chromosomes, leaving the majority with different expression levels in males and females. These findings warrant a re-examination of the evolutionary forces underlying dosage compensation.

Figure I

Chromosome divergence causes gene-dose differences between the sexes. (a) As the Y-chromosome-coding content degrades, an increasing number of genes on the X chromosome are present in different doses in males and females (shown in red). (b) This difference in gene dose ultimately causes gene transcription differences between the sexes.

Figure I

Global dosage-compensating mechanisms. Gene expression levels are indicated by chromosome width, levels of expected normal expression are indicated in dark blue, and hyper-transcription above this level is indicated in light blue. (a) In therian mammals, one X is inactivated in females (indicated by the thin white line) [15], then the active X is hyper-transcribed in both sexes to equalize expression levels with autosomal genes [37]. (b) In Drosophila, parity between the sexes is achieved through hyper-transcription of the male X chromosome, a process that also equalizes expression between the X and the autosomes [43,44]. (c) In C. elegans, hyper-transcription occurs for X chromosomes in both sexes [45], achieving X:A parity in males. However, X:A >1 in hermaphrodites, and a second hermaphrodite-specific chromosome-wide countering mechanism returns transcription in this sex to X:A parity (shown in white) [46,47].

Figure 1

Transcriptional profile for hypothetical local dosage compensation in a female heterogametic animal. Although some randomly distributed crucial genes are compensated locally (*), the vast majority show 1.5 times higher expression in males as a result of gene-dose differences.

Figure 2

Local dosage compensation in birds and Lepidopterans. In females (ZW), gene expression levels for some genes are hyper-transcribed locally, and the remaining genes are expressed normally. This produces an overall Z:A transcription ratio ≈0.8 in females. Gene expression levels are indicated by chromosome width, with the expected normal expression level indicated in dark blue, and hyper-transcription above this level indicated in light blue.

Figure 3

The evolution of internal gestation and X-chromosome inactivation in mammals. Between 180 and 210 MYA, the evolution of internal gestation led to the origin of live-bearing in the therian mammals (marsupials and eutherians). X-chromosome inactivation also originated on the branch separating the monotremes and therians, and at first involved only the paternal copy. After the divergence of the eutherians, this inactivation progressed to include either copy of the X, randomly determined in each cell early in development. Triangle width corresponds approximately to species diversity within the three mammalian clades.