Sex-chromosome dosage compensation
Sex Chromosome Dosage Compensation
Sex chromosome dosage compensation is a biological mechanism that balances the expression of genes between organisms with different numbers of sex chromosomes. This process is crucial in species where males and females have different numbers of sex chromosomes, such as in mammals, birds, and some insects. Without dosage compensation, the imbalance in gene expression could lead to detrimental effects on development and survival.
Mechanisms of Dosage Compensation
Dosage compensation can occur through various mechanisms, depending on the species. The primary goal is to equalize the expression of X-linked genes between the sexes.
X-Inactivation in Mammals
In mammals, dosage compensation is achieved through a process called X-inactivation. In female mammals, which have two X chromosomes, one of the X chromosomes is randomly inactivated in each cell. This inactivation is mediated by the XIST gene, which produces an RNA molecule that coats the X chromosome and silences its gene expression.
Hypertranscription in Drosophila
In Drosophila melanogaster, males have one X chromosome and females have two. Dosage compensation is achieved by hypertranscription of the single X chromosome in males. This is facilitated by the Male-Specific Lethal (MSL) complex, which binds to the X chromosome and increases its transcriptional activity.
Dosage Compensation in C. elegans
In the nematode Caenorhabditis elegans, dosage compensation is achieved by reducing the transcriptional output of both X chromosomes in hermaphrodites (XX) to match the single X chromosome in males (XO). This is accomplished by the dosage compensation complex (DCC), which binds to the X chromosomes and reduces their transcriptional activity by half.
Z Dosage Compensation in Birds
In birds, the sex chromosomes are designated as Z and W, with males being ZZ and females ZW. Dosage compensation in birds is less understood, but it is believed that there is partial compensation of Z-linked genes in females, possibly through upregulation of the Z chromosome in females or downregulation in males.
Evolutionary Perspectives
Dosage compensation mechanisms have evolved independently in different lineages, reflecting the diverse evolutionary pressures and constraints faced by different organisms. The evolution of these mechanisms is closely tied to the evolution of sex chromosomes themselves, which often arise from autosomes that acquire sex-determining functions.
Implications for Development and Disease
Proper dosage compensation is essential for normal development and function. Disruptions in dosage compensation can lead to developmental abnormalities and diseases. For example, improper X-inactivation in humans can result in conditions such as Turner syndrome and Klinefelter syndrome.
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Contributors: Prab R. Tumpati, MD