• Dosage Compensation: A Mechanism to Equalize X-linked Gene Products Between the Sexes

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    • Keywords


      Dosage compensation, X-linked genes, Barr body, XIST, heterochromatisation, X-linked disorders.

    • Abstract


      The sex chromosomes evolved from a pair of autosomes thatdeviated over a period of time, with one chromosome losingmost of its genes. In many animal groups, females have twoX-chromosomes—a large chromosome with numerous genes.Males have one X and a Y chromosome, which has lost mostgenes except those involved in sex determination and fertility.Thusmales are effectivelymonosomic for the X-chromosome.Monosomy being lethal for other chromosomes, organismsevolved amechanismcalled ‘dosage compensation’ (DC) whichquantitatively equalizes X-linked gene products between thesexes, compensating for their numerical disparity (dosage).Best studied in Drosophila, Caenorhabditis elegans, andmammals,different species adopt different mechanisms of DC. InDrosophila, genes on the male X-chromosome are twice as activeas on each X-chromosome in females. In C. elegans, DCis achieved by the lowered activity of each X-chromosome inXX individuals vis-a-vis the male X. In mammals, the inactivationof an entire X-chromosome in the female results inthe parity between the two sexes. Despite the difference ingross mechanisms, the molecular processes achieving DC areuniform due to chromatin modifications (histone acetylation,methylation, and DNA methylation) and synthesis of variousnoncoding RNAs (lncRNAs ). Together, they regulate the X chromosomeactivity. In mammals, a lncRNA from the inactive X—XIST (X-inactive specific transcript)—binds with thesame X to initiate inactivation. X-chromosome inactivation(XCI) in humans reveals interesting mechanisms for en blocregulation of gene function, as well as modifiers of Mendelian inheritance patterns in genetic disorders.

    • Author Affiliations


      Rajiva Raman1

      1. Cytogenetics Laboratory Banaras Hindu University Varanasi 221 005, India.
    • Dates


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