Mammalian sex determination is regulated by chromosomes.
- Females have two X chromosomes. (XX)
- Males have a single X and a small Y. (XY)
- The X and Y chromosome are morphologically and functionally different from each other.
- Evolutionary studies have shown that the Y was once the homologous pair for X.
- It is only in the last 5 years that we have some idea about how these two types of chromosomes may be regulated and genes of importance located upon them.
In females - the main scientific problem was understanding gene dosage, only one copy of X chromosome is needed to be genetically active the other copy is inactivated (More? X Inactivation.
About the X Chromosome
- 155 million base pairs
- In contrast to the Y chromosome, the X chromosome contains about 5% of the haploid genome and encodes house-keeping and specialized functions.
- Genes such as Wnt-4 and DAX-1 necessary for initiation of female pathway ovary development
- An early discovery (1961) was that in order to have correct levels of X chromosome gene/protein expression (gene dosage), females must "inactivate" a single copy of the X chromosome in each and every cell. The initiator of the X inactivation process was discovered (1991) to be regulated by a region on the inactivating X chromosome encoding an X inactive specific transcript (XIST), that acts as RNA and does not encode a protein.
- The genetic content of the X chromosome has been strongly conserved between species because these genes have become adapted to working as a single dose - Ohno's law
- X inactivation occurs randomly throughout the embryo, generating a mosaic of maternal and paternally derived X chromosome activity in all tissues and organs. This can be seen in the fur colour of tortoiseshell cats.
In males - the main scientific problem was understanding what on the Y chromosome determined "maleness", and how this is done.
About the Y Chromosome
- 59 million base pairs, hypervariable in length, mostly non-functional repeats
- Current known protein-coding genes = 48 including SRY
- SRY encodes a 204 amino acid protein that is a member of the HMG (High mobility group) box class of DNA-binding proteins. Transcription factors bind to specific sites of DNA and regulates the transcription (expression) of other genes.