Dosage compensation
Encyclopedia
Dosage compensation, also known as Ohno's Hypothesis, is a hypothetical genetic regulatory mechanism which operates to equalize the phenotypic expression of characteristics determined by genes on the X chromosome
so that they are equally expressed in the human XY male
and the XX female
. In 2006, literature was in support of this hypothesis. More recently (2008, 2011), the general consensus in literature refutes this hypothesis.
and the round worm Caenorhabditis elegans
.
Species can have different mechanisms of dosage compensation. In human females (XX), one chromosome is inactivated (see X-inactivation
), resulting in a heterochromatic and largely genetically inactive Barr body
. Drosophila males (XY) double the expression of genes along the X chromosome. In C. elegans hermaphrodites (XX), both X chromosomes are partially repressed. Any of these mechanisms results in balancing the relative gene expression between males and females (or, in the case of C. elegans, hermaphrodites and males).
In plants (which lack dimorphic sex chromosomes), dosage compensation can occur when aberrant meiotic events or mutations result in either aneuploidy
or polyploidy. Genes on the affected chromosome may be upregulated or down-regulated to compensate for the change in the normal number of chromosomes present.
In Humans*:
Women with two normal X chromosomes have the same blood levels of X-chromosome protein products, such as factor VIII, as normal men, who of course have only one X chromosome. An exception to this phenomenon of dosage compensation is the level of steroid sulfatase in blood, which is increased in women compared with men. Not surprisingly it has been shown that the locus for steroid sulfatase (deficiency of which causes a skin disorder known as ichthyosis) is in the pseudoautosomal region
.
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
so that they are equally expressed in the human XY male
Male
Male refers to the biological sex of an organism, or part of an organism, which produces small mobile gametes, called spermatozoa. Each spermatozoon can fuse with a larger female gamete or ovum, in the process of fertilization...
and the XX female
Female
Female is the sex of an organism, or a part of an organism, which produces non-mobile ova .- Defining characteristics :The ova are defined as the larger gametes in a heterogamous reproduction system, while the smaller, usually motile gamete, the spermatozoon, is produced by the male...
. In 2006, literature was in support of this hypothesis. More recently (2008, 2011), the general consensus in literature refutes this hypothesis.
Older Research (May no longer be valid)
Dosage compensation may occur in other organisms like the fruit fly Drosophila melanogasterDrosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
and the round worm Caenorhabditis elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
.
Species can have different mechanisms of dosage compensation. In human females (XX), one chromosome is inactivated (see X-inactivation
X-inactivation
X-inactivation is a process by which one of the two copies of the X chromosome present in female mammals is inactivated. The inactive X chromosome is silenced by packaging into transcriptionally inactive heterochromatin...
), resulting in a heterochromatic and largely genetically inactive Barr body
Barr body
A Barr body is the inactive X chromosome in a female somatic cell, rendered inactive in a process called lyonization, in those species in which sex is determined by the presence of the Y or W chromosome rather than the diploidy of the X or Z...
. Drosophila males (XY) double the expression of genes along the X chromosome. In C. elegans hermaphrodites (XX), both X chromosomes are partially repressed. Any of these mechanisms results in balancing the relative gene expression between males and females (or, in the case of C. elegans, hermaphrodites and males).
In plants (which lack dimorphic sex chromosomes), dosage compensation can occur when aberrant meiotic events or mutations result in either aneuploidy
Aneuploidy
Aneuploidy is an abnormal number of chromosomes, and is a type of chromosome abnormality. An extra or missing chromosome is a common cause of genetic disorders . Some cancer cells also have abnormal numbers of chromosomes. Aneuploidy occurs during cell division when the chromosomes do not separate...
or polyploidy. Genes on the affected chromosome may be upregulated or down-regulated to compensate for the change in the normal number of chromosomes present.
In Humans*:
Women with two normal X chromosomes have the same blood levels of X-chromosome protein products, such as factor VIII, as normal men, who of course have only one X chromosome. An exception to this phenomenon of dosage compensation is the level of steroid sulfatase in blood, which is increased in women compared with men. Not surprisingly it has been shown that the locus for steroid sulfatase (deficiency of which causes a skin disorder known as ichthyosis) is in the pseudoautosomal region
Pseudoautosomal region
The pseudoautosomal regions, PAR1 and PAR2 are homologous sequences of nucleotides on the X and Y chromosomes.The pseudoautosomal regions get their name because any genes located within them are inherited just like any autosomal genes...
.
Further reading
- Casci, T. Dosage compensation: What dosage compensation. Nature Reviews Genetics (2011). http://www.nature.com/nrg/journal/v12/n1/full/nrg2921.html
- Orr, H.A. (1990). The American Naturalist. 136(6):759-770.
- Mable, B.K. (2004). Biological Journal of the Linnean Society. 82:453-466.