What’s Gene Dosing?

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Gene dosage refers to the number of copies of a gene present in an organism’s genome. Dosage compensation ensures gene expression remains at adequate levels in both males and females, despite genetic imbalance caused by different genes. Different organisms have different means of regulating gene expression, such as X inactivation in humans and doubling gene expression on the male X chromosome in fruit flies. C. elegans presents an interesting case, with partial repression of gene expression on both X chromosomes in hermaphrodites.

Gene dosage refers to the number of copies of a gene present in an organism’s genome or in the complete “library” of genetic information. Many organisms, including humans, store genetic information on paired chromosomes. Each member of a pair of chromosomes contributes a “single dose” of the genes contained in that chromosome. Sex chromosomes, however, tend to differ between males and females; human males have a single X chromosome and a single Y chromosome while human females have a pair of X chromosomes. Various regulatory processes known as “dosage compensation” are in place to ensure that gene dosage remains at adequate levels in both males than in females, despite the genetic imbalance caused by different genes.

In general, more copies of a gene – or higher gene dosage – will result in increased expression of the proteins that the genes code for. To a significant extent, however, genes on the male and female sex chromosomes are expressed at comparable levels despite the difference in gene dosage. If this were not the case, females with their two X chromosomes could overexpress certain genes, or males with their single X and Y chromosomes could underexpress certain genes. Both of these alternatives could cause severe mutations or death, so it is important that the genes are expressed at comparable levels despite the difference in gene dosage.

A set of regulatory mechanisms and processes known as dosage compensation is responsible for maintaining gene expression at appropriate levels. Different organisms have different means of regulating the expression of their genes and some even make use of multiple methods of dosage compensation. Gene expression in human females is regulated through X inactivation, whereby one of the female’s two X chromosomes becomes an inactive “Barr body”. The result of X inactivation is that males and females each have only one X chromosome which actually expresses its genetic information and contributes to the gene dosage.

In some organisms, such as the fruit fly or Drosophila melanogaster, the expression of genes on the male X chromosome is doubled to match the gene dosage of the two female X chromosomes. The roundworm, or C. elegans, presents an interesting case, as it most commonly exists as a hermaphrodite with two X chromosomes, although some have only a single sex chromosome, X, and are classified as male. Dosage compensation in C. elegans results in partial repression of gene expression on both X chromosomes in hermaphrodites.




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