12.18:
Dosage Compensation
In many organisms, females have two copies of an X chromosome, whereas males may have one X and one Y chromosome or one X chromosome. This means that the sexes differ in their dose of X chromosome genes.
Through a process called dosage compensation, an organism either upregulates or downregulates certain genes to equalize gene expression between sexes of the same species. This occurs via three mechanisms.
The first mechanism of dosage compensation can be found in humans. Initially, a female embryo has two active X chromosomes. The inactivation process begins at the blastocyst stage.
Both X chromosomes have an X chromosome inactivation center or X-I-C which has an X-I-S-T gene.
Blocking factors bind to the X-I-S-T gene of one X chromosome, and block its transcription.
The X-I-S-T gene of the other X chromosome produces an X chromosome-specific transcript, or X-I-S-T, which is an RNA.
This RNA wraps around the first X chromosome. Then, other proteins, called the X-I-S-T associated proteins, bind to the X-I-S-T RNA and begin to compact the chromosome, resulting in the formation of a Barr body.
All female somatic cells have one Barr body, whereas male somatic cells do not have any Barr bodies, as they have only one X chromosome.
The second mechanism of dosage compensation can be found in Drosophila.
Male Drosophila have a ratio of one X chromosome to two sets of autosomes. In females, it’s two to two.
As a result, in developing males, two deadpan proteins block the binding of two sisterless proteins on the sex-lethal gene.
The sex-lethal gene becomes non-functional, which results in the translation of the male-specific lethal gene or M-S-L gene.
The M-S-L proteins bind to X-linked genes on the male X chromosome and increase their expression two-fold.
C. elegans follows the third mechanism. Here, a worm with two X chromosomes is a hermaphrodite, while a worm with one X chromosome is a male.
In the hermaphroditic worms, the dosage compensation complex, or D-C-C, binds to both X chromosomes and down-regulates the expression of genes on both X chromosomes.
In this system, half of the genes are active in one X chromosome, and the rest of the genes are active in the other X chromosome.
12.18:
Dosage Compensation
In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have different copies of X-linked genes that may create an imbalance. To avoid this, animals have evolved mechanisms to compensate for the differences in X-linked genes between the two sexes.
There are three main mechanisms of dosage compensation. The first mechanism is found in female mammals, which inactivates one of the X chromosomes in females. The second mechanism is observed in male Drosophila, where they show a two-fold increase in the expression of X-linked genes. The third mechanism is documented in C.elegans, where the hermaphrodites decrease the transcription of both the X chromosomes by half.
In mammals, the X-inactivation is regulated by two noncoding, complementary RNAs—XIST and TSIX. The XIST is a noncoding RNA produced by one of the X chromosomes in females. It binds to the X chromosome that produces it and inhibits all other genes from that chromosome. Interestingly, XIST is only made from the inactivated X chromosome and not from the other one. The active copy of the X chromosome produces an antagonistic RNA molecule called TSIX that inhibits XIST activity. Therefore, the inactivated X chromosome produces XIST, and the functional copy of the chromosome produces TSIX.
Suggested Reading
- X chromosome: X inactivation. Nature Education 1(1):24
- Lin, Hong, Vibhor Gupta, Matthew D. VerMilyea, Francesco Falciani, Jeannie T. Lee, Laura P. O'Neill, and Bryan M. Turner. "Dosage compensation in the mouse balances up-regulation and silencing of X-linked genes." PLoS Biol 5, no. 12 (2007): e326.
- Brockdorff, Neil, and Bryan M. Turner. "Dosage compensation in mammals." Cold Spring Harbor perspectives in biology 7, no. 3 (2015): a019406.
- Disteche, Christine M. "Dosage compensation of the sex chromosomes." Annual review of genetics 46 (2012): 537-560.