Dosage compensation

Dosage compensation is the process by which organisms equalize the expression of genes between members of different biological sexes. Across species, different sexes are often characterized by different types and numbers of sex chromosomes. In order to neutralize the large difference in gene dosage produced by differing numbers of sex chromosomes among the sexes, various evolutionary branches have acquired various methods to equalize gene expression among the sexes. Because sex chromosomes contain different numbers of genes, different species of organisms have developed different mechanisms to cope with this inequality. Replicating the actual gene is impossible; thus organisms instead equalize the expression from each gene. For example, in humans, females (XX) silence the transcription of one X chromosome of each pair, and transcribe all information from the other, expressed X chromosome. Thus, human females have the same number of expressed X-linked genes as do human males (XY), both sexes having essentially one X chromosome per cell, from which to transcribe and express genes.One logical way to equalize gene expression amongst males and females that follow a XX/XY sex differentiation scheme would be to decrease or altogether eliminate the expression of one of the X chromosomes in an XX, or female, homogametic individual, such that both males and females then express only one X chromosome. This is the case in many mammalian organisms, including humans and mice.Another mechanism common for achieving equal X-related genetic expression between males and females involves two-fold increased transcription of a single male X chromosome. Thus, heterogametic male organisms with one X chromosome may match the level of expression achieved in homogametic females with two active X chromosomes. This mechanism is observed in Drosophila.Other species that do not follow the previously discussed conventions of XX females and XY males must find alternative ways to equalize X-linked gene expression among differing sexes. For example, in Caenorhabditis elegans (or C. elegans), sex is determined by the ratio of X chromosomes relative to autosomes; worms with two X chromosomes (XX worms) develop as hermaphrodites, whereas those with only one X chromosome (XO worms) develop as males. This system of sex determination is unique, because there is no male specific chromosome, as is the case in XX/XY sex determination systems. However, as is the case with the previously discussed mechanisms of dosage compensation, failure to express X-linked genes appropriately can still be lethal.The ZZ/ZW sex system is used by most birds, as well as some reptiles and insects. In this system the Z is the larger chromosome so the males (ZZ) must silence some genetic material to compensate for the female's (ZW) smaller W chromosome. Instead of silencing the entire chromosome as humans do, male chickens (the model ZZ organism) seem to engage in selective Z silencing, in which they silence only certain genes on the extra Z chromosome. Thus, male chickens express an average of 1.4-1.6 of the Z chromosome DNA expressed by female chickens. The Z chromosome expression of male zebra finches and chickens is higher than the autosomal expression rates, whereas X chromosome expression in female humans is equal to autosomal expression rates, illustrating clearly that both male chickens and male zebra finches practice incomplete silencing. Few other ZZ/ZW Systems have been analyzed as thoroughly as the chicken; however a recent study on silkworms revealed similar levels of unequal compensation across male Z chromosomes. Z-specific genes were over-expressed in males when compared to females, and a few genes had equal expression in both male and female Z chromosomes.