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12.17: Dosage Compensation
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Molecular Biology

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Dosage Compensation
 
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12.17: 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.


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