Genetics - A. V. Sivolob 2008

Genetics of Multicellular Eukaryotes
Sex Genetics
Gene Dosage Compensation and the Evolution of Sex Chromosomes

Since the homogametic sex possesses two identical sex Chromosomes, the number of genes contained within these chromosomes—and consequently, their protein products (Gene dosage)—is twice as large as in the heterogametic sex. An excess or Deficiency of certain Proteins can adversely affect Organism development; therefore, Evolutionary Processes have given rise to mechanisms that "equalize" the quantity of sex chromosome gene products in females and males at the relevant Selection/3.html">Stages of development, known as dosage compensation mechanisms.

There are two pathways for this compensation. In Drosophila males, hyperactivation of the single X chromosome occurs by maintaining a decondensed state of the Chromatin fiber. This process involves the products of five genes (MSL proteins) that form a multi-protein complex binding to the X chromosome: MSL complexes maintain fiber diffusivity and recruit chromatin remodeling and histone acetyltransferase complexes (see Chapter 2), which significantly increases transcriptional initiation efficiency. Gene compensation is controlled by the key Sxl gene mentioned earlier: in females, the functional Sxl protein prevents MSL proteins from localizing on the X chromosomes, thereby averting hyperactivation.

Mammals exhibit the opposite mechanism of gene compensation through the inactivation of one X chromosome in females. Inactivation occurs at Cytology/cytology/16.html">Early stages of zygote Cleavage (16–32 blastomeres), and the choice of which chromosome becomes inactivated is random. Thus, in both females and males, only a single X chromosome is active in somatic Cells. Females heterozygous for X-linked genes are mosaics (some cells express the dominant allele, while others express the recessive one).

The precise mechanism of X chromosome inactivation in mammalian females is not yet fully understood. It is known that inactivation initiates from a specific region of the X chromosome designated as Xic (X inactivation center). Xic contains several genes, one of which—the Xist gene—is expressed exclusively on the X chromosome destined for inactivation. The product of this gene is a relatively long, non-coding RNA molecule. Xist RNA molecules bind to the X chromosome along almost its entire length and recruit specific proteins that drive heterochromatinization. The inactivated X chromosome appears in interphase nuclei as a compact heterochromatic body near the nuclear membrane—the Barr body (named after Murray Barr). When multiple X chromosomes are present (XXY, XXXY, etc.), only one remains active; the number of Barr bodies is always equal to the total number of X chromosomes minus one.

Because organisms with heteromorphic sex chromosomes belong to different kingdoms, sex chromosomes likely evolved independently on multiple occasions. This Conclusion is further supported by the fact that even within a single taxonomic group, such as reptiles, there are species with chromosomal Sex Determination as well as those lacking sex chromosomes entirely (where sex is determined by ambient Temperature).

Understandably, sex chromosomes originated from an ancestral pair of autosomes, as evidenced by the presence of pseudoautosomal regions. Most likely, homomorphic (morphologically identical) sex chromosomes arose first, followed later by heteromorphic ones. For instance, in more ancestral snake species, sex chromosomes are homomorphic, with the sole difference lying in their Replication timing: the Z chromosome replicates early, whereas the W chromosome replicates at the end of the S phase of the Cell Cycle. Younger snake species already possess heteromorphic sex chromosomes. Evidently, one of the sex chromosomes evolves via chromosomal rearrangements; at least in mammals, the Y chromosome is believed to have originated from an X chromosome that underwent numerous deletions.