Sex chromosome

In humans, each cell nucleus contains 23 pairs of chromosomes, a total of 46 chromosomes. The first 22 pairs are called autosomes. Autosomes are homologous chromosomes i.e. chromosomes which contain the same genes (regions of DNA) in the same order along their chromosomal arms. The chromosomes of the 23rd pair are called allosomes consisting of two X chromosomes in most females, and an X chromosome and a Y chromosome in most males. Females therefore have 23 homologous chromosome pairs, while males have 22. The X and Y chromosomes have small regions of homology called pseudoautosomal regions.

The X chromosome is always present as the 23rd chromosome in the ovum, while either an X or a Y chromosome can be present in an individual sperm.[5] Early in female embryonic development, in cells other than egg cells, one of the X chromosomes is randomly and permanently partially deactivated: In some cells the X chromosome inherited from the mother is deactivated, while in others the X chromosome from the father is deactivated. This ensures that both sexes always have exactly one functional copy of the X chromosome in each body cell. The deactivated X-chromosome is silenced by repressive heterochromatin that compacts the DNA and prevents expression of most genes (see X-inactivation). This compaction is regulated by PRC2 (Polycomb Repressive Complex 2).[6]

All diploid organisms with allosome-determined sex get half of their allosomes from each of their parents. In mammals, females are XX, they can pass along either of their X's, and since the males are XY they can pass along either an X or a Y. For a mammal to be chromosomally female, the individual must receive an X chromosome from both parents, whereas to be chromosomally male, the individual must receive a X chromosome from their mother and a Y chromosome from their father. It is thus the male's sperm that determines the sex of each offspring in humans.

However, a small percentage of humans have a divergent sexual development, known as intersex. This can result from allosomes that are neither XX nor XY. It can also occur when two fertilized embryo fuse, producing a chimera that might contain two different sets of DNA one XX and the other XY. It could also result from exposure, often in utero, to chemicals that disrupt the normal conversion of the allosomes into sex hormones and further into the development of either ambiguous outer genitalia or internal organs.[7]

On a deeper level, however, sex determination goes beyond the acquirement of XX or XY sex-chromosome pairs. There are questions about how, on a molecular level, allosomes influence the creation of “femaleness” or “maleness.”

Previous theories on Sex Determination

Ever since the discovery of X-inactivation through research into Calico cats, it has been postulated that X-inactivation plays a role in genetic sex determination in humans. Initially, there were many theories as to how exactly X-inactivation influences sex. To understand one such theory, you can take the following scenario into consideration: a DNA sequence that is concerned with the creation of a male-trait is regulated by a regulatory DNA sequence. If the regulatory DNA sequence allows the main sequence to be expressed, the male-trait will appear in the phenotype, otherwise not. An explanation for this theory is that the X-chromosome simply inactivates in the presence of another X-chromosome; this causes XX-chromosome humans to have a lower frequency of the regulatory gene (given that both X and Y chromosomes have an equal frequency of the regulator) and so the expression of the male trait is prevented from appearing in the phenotype.[8]

A picture depicting the locus of the SRY gene on the Y-chromosome.

Allosomes not only carry the genes that determine male and female traits, but also those for some other characteristics as well. Genes that are carried by either sex chromosome are said to be sex linked. Sex linked diseases are passed down through families through one of the X or Y chromosomes. Since only men inherit Y chromosomes, they are the only ones to inherit Y-linked traits. Men and women can get the X-linked ones since both inherit X chromosomes.[15]

An allele is either said to be dominant or recessive. Dominant inheritance occurs when an abnormal gene from one parent causes disease even though the matching gene from the other parent is normal. The abnormal allele dominates. Recessive inheritance is when both matching genes must be abnormal to cause disease. If only one gene in the pair is abnormal, the disease does not occur, or is mild. Someone who has one abnormal gene (but no symptoms) is called a carrier. A carrier can pass this abnormal gene to his or her children.[16] X chromosome carry about 1500 genes, more than any other chromosome in the human body. Most of them code for something other than female anatomical traits. Many of the non-sex determining X-linked genes are responsible for abnormal conditions. The Y chromosome carries about 78 genes. Most of the Y chromosome genes are involved with essential cell house-keeping activities and sperm production. Only one of the Y chromosome genes, the SRY gene, is responsible for male anatomical traits. When any of the 9 genes involved in sperm production are missing or defective the result is usually very low sperm counts and infertility.[17] Examples of mutations on the X chromosome include more common diseases such as color blindness, hemophilia, and fragile-X syndrome.

• Color blindness or color vision deficiency is the inability or decreased ability to see color, or perceive color differences, under normal lighting conditions. Color blindness affects many individuals in the population. There is no actual blindness, but there is a deficiency of color vision. The most usual cause is a fault in the development of one or more sets of retinal cones that perceive color in light and transmit that information to the optic nerve. This type of color blindness is usually a sex-linked condition. The genes that produce photopigments are carried on the X chromosome; if some of these genes are missing or damaged, color blindness will be expressed in males with a higher probability than in females because males only have one X chromosome.
• Hemophilia refers to a group of bleeding disorders in which it takes a long time for the blood to clot. This is referred to as X-Linked recessive.[18] Hemophilia is much more common in males than females because males are hemizygous. They only have one copy of the gene in question and therefore express the trait when they inherit one mutant allele. In contrast, a female must inherit two mutant alleles, a less frequent event since the mutant allele is rare in the population. X-linked traits are maternally inherited from carrier mothers or from an affected father. Each son born to a carrier mother has a 50% probability of inheriting the X-chromosome carrying the mutant allele.
  • Queen Victoria was a carrier of the gene for hemophilia. She passed on the harmful allele to one of her four sons and at least two of her five daughters. Her son Leopold had the disease and died at age 30. As a result of marrying into other European royal families, the princesses Alice and Beatrice spread hemophilia to Russia, Germany, and Spain. By the early 20th century, ten of Victoria's descendants had hemophilia. All of them were men, as expected.[15]
• Fragile X syndrome is a genetic condition involving changes in part of the X chromosome. It is the most common form of inherited intellectual disability (mental retardation) in males. It is caused by a change in a gene called FMR1. A small part of the gene code is repeated on a fragile area of the X chromosome. The more repeats, the more likely there is to be a problem. Males and females can both be affected, but because males have only one X chromosome, a single fragile X is likely to affect them more. Most fragile-X males have large testes, big ears, narrow faces, and sensory processing disorders that result in learning disabilities.[19]

Other complications include:

• 46,XX testicular disorder of sex development, also called XX male syndrome, is a condition in which individuals with two X chromosomes in each cell, the pattern normally found in females, have a male appearance. People with this disorder have male external genitalia. In most people with 46,XX testicular disorder of sex development, the condition results from an abnormal exchange of genetic material between chromosomes (translocation). This exchange occurs as a random event during the formation of sperm cells in the affected person's father. The SRY gene (which is on the Y chromosome) is misplaced in this disorder, almost always onto an X chromosome. Anyone with an X chromosome that carries the SRY gene will develop male characteristics despite not having a Y chromosome.[20]

• Fisher's principle
• Haldane's rule
• XY sex-determination system
• ZW sex-determination system
• X0 sex-determination system