EXTINCTION OF MEN : A MYTH OR A REALITY ?

The Y chromosome is a never-ending source of fascination particularly to men because it bears genes that determine maleness & make sperm. It’s also small & seriously weird; it carries few genes and is full of junk DNA that makes it horrendous to sequence. 

The sex of human & other mammal babies is decided by a male-determining gene on the Y chromosome. But the human Y chromosome is degenerating and may disappear in a few million years, leading to our extinction unless we evolve a new sex gene. However two branches of rodents have already lost their Y chromosome and have survived successfully.

In humans, as in other mammals, females have two X chromosomes and males have a single X and a puny little chromosome called Y. The names have nothing to do with their shape; the X stood for “unknown”.

The X contains about 900 genes that do all sorts of jobs unrelated to sex. But the Y contains few genes (about 55) and a lot of non-coding DNA – simple repetitive DNA that doesn’t seem to do anything.

But the Y chromosome  contains an all-important gene that kick-starts male development in the embryo. At about 12 weeks after conception, this master gene switches on others that regulate the development of a testis. The embryonic testis makes male hormones (testosterone & its derivatives), which ensures the baby develops as a boy.

This master sex gene was identified as SRY (sex region on the Y) in 1990. It works by triggering a genetic pathway starting with a gene called SOX9 which is key for male determination in all vertebrates, although it does not lie on sex chromosomes.

DISAPPEARING Y CHROMOSOME 

Most mammals have an X & Y chromosome similar to ours; an X with lots of genes, and a Y with SRY plus a few others. This system comes with problems because of the unequal dosage of X genes in males & females. 

Australia’s platypus has completely different sex chromosomes, more like those of birds. In platypus, the XY pair is just an ordinary chromosome, with two equal members. This suggests the mammal X and Y were an ordinary pair of chromosomes not that long ago. 

This must mean the Y chromosome has lost 900–55 active genes over the 166 million years that humans and platypus have been evolving separately. That’s a loss of about five genes per million years. At this rate, the last 55 genes will be gone in 11 million years.

RODENTS WITH NO ‘Y’ CHROMOSOMES

The mole voles of eastern Europe and the spiny rats of Japan each boast some species in which the Y chromosome, and SRY, have completely disappeared. The X chromosome remains, in a single or double dose in both sexes.  

Although it’s not yet clear how the mole voles determine sex without the SRY gene, a team led by Hokkaido University biologist Asato Kuroiwa has had more luck with the spiny rat – a group of three species on different Japanese islands, all endangered. 

Kuroiwa’s team discovered most of the genes on the Y of spiny rats had been relocated to other chromosomes. But she found no sign of SRY, nor the gene that substitutes for it.

What they discovered was a tiny difference near the key sex gene SOX9, on chromosome 3 of the spiny rat. A small duplication (only 17,000 base pairs out of more than 3 billion) was present in all males and no females.

They suggest this small bit of duplicated DNA contains the switch that normally turns on SOX9 in response to SRY. When they introduced this duplication into mice, they found that it boosts SOX9 activity, so the change could allow SOX9 to work without SRY.

FUTURE OF MEN 

Some lizards & snakes are female-only species and can make eggs out of their own genes via what’s known as parthenogenesis. But this can’t happen in humans or other mammals because we have at least 30 crucial “imprinted” genes that work only if they come from the father via sperm. The new finding supports an alternative possibility – that humans can evolve a new sex determining gene.  

However, evolution of a new sex determining gene comes with risks. If more than one new system evolves in different parts of the world, it could lead to the separation of new species, which is exactly what has happened with mole voles and spiny rats.

The human X & Y chromosomes evolved from a pair of autosomes approximately 180 million years ago. Despite their shared evolutionary origin, extensive genetic decay has resulted in the human Y chromosome losing 97% of its ancestral genes while gene content and order remain highly conserved on the X chromosome. 

Five ‘stratification’ events, most likely inversions, reduced the Y chromosome’s ability to recombine with the X chromosome across the majority of its length and subjected its genes to the erosive forces associated with reduced recombination. 

The remaining functional genes are ubiquitously expressed, functionally coherent, dosage-sensitive genes, or have evolved male-specific functionality. It is unknown, however, whether functional specialization is a degenerative phenomenon unique to sex chromosomes, or if it conveys a potential selective advantage aside from sexual antagonism.

The degenerative nature of the Y chromosome has led some researchers to suggest it may lose all functional genes and become extinct. This has resulted in the majority of the Y chromosome’s gene content being inherited as a unit, known as the human MSY (male-specific region of the Y chromosome).

Recent research, however, suggests that the Y chromosome has maintained a stable assortment of genes for the last 25 million years . The degeneration  is highly correlated with the age of X-Y gene pairs within each stratum. The oldest of which contains only four remaining genes, including the sex-determining factor SRY.

The remaining functional genes in the human MSY fall into three classes: X-degenerate, ampliconic, and X-transposed. The X-transposed sequences are a result of an X-to-Y transposition that occurred after the divergence of the human and chimpanzee lineages, approximately 3-4 million years ago.

These sequences remain 99% identical to their X counterparts. In contrast, the X-degenerate sequences are single-copy MSY genes that are surviving relics of the ancestral autosomes from which the sex chromosomes evolved.   

With the notable exception of SRY, these genes are functionally coherent, and ubiquitously expressed. Their homologous X counterparts also disproportionately escape X-inactivation and are subject to stronger purifying selection than other X-linked genes. 

The last class of functional genes in the MSY consists of nine protein-coding gene families that have undergone various levels of amplification.  Wide-spread gene loss accompanied by preferential retention appears to be a unique phenomenon. A review of genomic evolution, however, suggests that these trends are not unique to the Y chromosome.

Recent research suggests that the ancestral vertebrate karyotype was much larger than previously estimated, consisting of an estimated 54 chromosomes resulting from two ancestral whole-genome duplication (WGD) events.

The majority of genes following a WGD event are rapidly lost or pseudogenized due to loss of function mutations. Consequently, a large portion of the ancestral vertebrate chromosomes has been subsequently lost through fusion in the descent of the human lineage.

Highly expressed genes, dosage-sensitive protein complexes & transcriptional and developmental regulators and signal transducers, however, are preferentially retained. Furthermore, these genes have been maintained through purifying selection, a trend that has been observed in ubiquitously expressed genes throughout the genome. 

The functional specificity and reduced expression are associated with relaxed purifying selection, suggesting that subfunctionalization of duplicated paralogs could result in differential tissue expression & accelerated protein divergence.

Two features set Y chromosomes apart from the rest of the genome; these are a lack of recombination on the Y over some or most of its length, and male-limited transmission of the non-recombining segment. Investigating Y chromosomes is challenging; their lack of recombination prevents classical linkage mapping studies, and their high content of repetitive and ampliconic sequences has excluded them from most genome sequencing projects.

Classical genetics studies have shown that Y chromosomes often encode nearly no genes, and indeed, some species have completely lost their Y. Genetic deterioration of the Y chromosome has occurred because unlike with the two X chromosomes in women, there is very little swapping of genetic material between the Y and X chromosome during reproduction. This means mutations and deletions in the Y chromosome are preserved between (male) generations. 

The X is fine because in females it gets to recombine with the other X but the Y never gets to recombine over almost its entire length, and shutting down that recombination has left the Y vulnerable to all these degenerative forces.