Faced with inequality: chicken do not have a general dosage compensation of sex-linked genes

Abstract

Background: The contrasting dose of sex chromosomes in males and females potentially introduces a large-scale imbalance in levels of gene expression between sexes, and between sex chromosomes and autosomes. In many organisms, dosage compensation has thus evolved to equalize sex-linked gene expression in males and females. In mammals this is achieved by X chromosome inactivation and in flies and worms by up- or down-regulation of X-linked expression, respectively. While otherwise widespread in systems with heteromorphic sex chromosomes, the case of dosage compensation in birds (males ZZ, females ZW) remains an unsolved enigma.

Results: Here, we use a microarray approach to show that male chicken embryos generally express higher levels of Z-linked genes than female birds, both in soma and in gonads. The distribution of male-to-female fold-change values for Z chromosome genes is wide and has a mean of 1.4-1.6, which is consistent with absence of dosage compensation and sex-specific feedback regulation of gene expression at individual loci. Intriguingly, without global dosage compensation, the female chicken has significantly lower expression levels of Z-linked compared to autosomal genes, which is not the case in male birds.

Conclusion: The pronounced sex difference in gene expression is likely to contribute to sexual dimorphism among birds, and potentially has implication to avian sex determination. Importantly, this report, together with a recent study of sex-biased expression in somatic tissue of chicken, demonstrates the first example of an organism with a lack of global dosage compensation, providing an unexpected case of a viable system with large-scale imbalance in gene expression between sexes.

Figure 1

Expression levels for individual Z-linked genes are higher in males than in females. Scatter plots of the relationship between log₂ hybridization intensities of individual genes in (a) soma and (b) gonads of male and female chicken embryos. The red line corresponds to twofold higher hybridization intensity in males than in females.

Figure 2

Higher fold-change expression sex difference for the Z chromsome than for individual autosomes. Box plots showing median of log2 male-to-female fold-change values per chromosome in (a) soma and (b) gonads. Boxes represent the mid 50% of the data (first and third quartiles) and whiskers extend to the minimum and maximum values that are not outliers (defined as >1.5 units away from first and third quartiles. Data from the Z chromosome is shown in red.

Figure 3

The distribution of fold-change values differ between Z-linked and autosomal genes. Fold-change values for autosomal (black) and Z-linked (red) genes in (a) soma and (b) gonads. Note different scales on y axes in (a) and (b).

Figure 4

Similar levels of male and female autosomal, and male but not female Z-linked, gene expression. Histograms of mean log₂ hybridization intensities for all genes, and unbiased genes (<1.2 fold-change), in (a) soma and (b) gonads. Male autosomal genes are shown in blue and female genes in red, whereas Z-linked genes in males are shown in yellow and in females in green. Error bars correspond to 95% confidence intervals.