- The Y chromosome has ~60 genes that are expressed specifically in testis.
- The male-specific genes are present in multiple copies in repeated chromosomal segments.
- Gene conversion between multiple copies allows the active genes to be maintained during evolution.
The sequence of the human genome has significantly extended our understanding of the role of the sex chromosomes. It is generally thought that the X and Y chromosomes have descended from a common (very ancient) autosome. Their development has involved a process in which the X chromosome has retained most of the original genes, whereas the Y chromosome has lost most of them.
The X chromosome behaves like the autosomes insofar as females have two copies and recombination can take place between them. The density of genes on the X chromosome is comparable to the density of genes on other chromosomes.
The Y chromosome is much smaller than the X chromosome and has many fewer genes. Its unique role results from the fact that only males have the Y chromosome, and there is only one copy, so Y-linked loci are effectively haploid, instead of diploid like all other human genes.
For many years, the Y chromosome was thought to carry almost no genes except for one (or more) sex-determining genes that determine maleness. The vast majority of the Y chromosome (>95% of its sequence) does not undergo crossing-over with the X chromosome, which led to the view that it could not contain active genes, because there would be no means to prevent the accumulation of deleterious mutations. This region is flanked by short pseudoautosomal regions that exchange frequently with the X chromosome during male meiosis. It was originally called the nonrecombining region, but now has been renamed as the male-specific region.
Detailed sequencing of the Y chromosome shows that the male-specific region contains three types of regions, as illustrated in Figure 3.25 (Skaletsky et al., 2003):
- The X-transposed sequences consist of a total of 3.4 Mb comprising some large blocks resulting from a transposition from band q21 in the X chromosome about 3-4 million years ago. This is specific to the human lineage. These sequences do not recombine with the X chromosome and have become largely inactive. They now contain only two active genes.
- The X-degenerate segments of the Y are sequences that have a common origin with the X chromosome (going back to the common autosome from which both X and Y have descended) and contain genes or pseudogenes related to X-linked genes. There are 14 active genes and 13 pseudogenes. The active genes have in a sense so far defied the trend for genes to be eliminated from chromosomal regions that cannot recombine at meiosis.
- The ampliconic segments have a total length of 10.2 Mb and are internally repeated on the Y chromosome. There are 8 large palindromic blocks. They include 9 protein-coding gene families, with copy numbers per family ranging from 2-35. The name “amplicon” reflects the fact that the sequences have been internally amplified on the Y chromosome.
Totaling the genes in these three regions, the Y chromosome contains many more genes than had been expected. There are 156 transcription units, of which half represent protein-coding genes, and half represent pseudogenes.
The presence of the active genes is explained by the fact that the existence of closely related genes copies in the ampliconic segments allows gene conversion between multiple copies of a gene to be used to regenerate active copies. The most common needs for multiple copies of a gene are quantitative (to provide more protein product) or qualitative (to code for proteins with slightly different properties or that are expressed in different times or places), but in this case the essential function is evolutionary. In effect, the existence of multiple copies allows recombination within the Y chromosome itself to substitute for the evolutionary diversity that is usually by provided by recombination between allelic chromosomes.
Most of the protein-coding genes in the ampliconic segments are expressed specifically in testis, and are likely to be involved in male development. If there are ~60 such genes out of a total human gene set of ~30,000, then the genetic difference between man and woman is ~0.2%.