Will Men Become Extinct?

Will men become extinct? It's entirely possible, according to recent scientific research performed on the single genetic element that makes a man a man: the Y chromosome. This conglomerate of nucleotides and proteins, whose sequence codes for only 23 distinct proteins¹, has been marked for eventual extinction by many geneticists. And yet, without it, and the male-specific proteins for which it codes (the majority of which are designated for reproduction), men would cease to exist.

All humans contain 23 pairs of chromosomes, totaling 46 in all. Females carry a full complement of 22 autosomal (non-sex) chromosome pairs, plus a pair of X sex chromosomes. Males also carry the 22 autosomal pairs, plus a single X and a single Y sex chromosome for the 23^rd pair. The X is equivalent in size to many of the other autosomal chromosomes and, in the female, to the other X sex chromosome. The Y chromosome is much smaller than the other autosomal chromosomes, and certainly much smaller than the X.

During the production of sex cells such as sperm and ova, these 23 chromosomal pairs match up and exchange genetic elements with each other. Alleles, which are the different forms that genes can take, are swapped between chromosome "twins". Bad alleles are swapped for better ones, or vice versa. In the end, once this gene shuffling exercise is over, all the chromosome partners end up with a completely new combination of genetic alleles -except for one particular pair. The Y chromosome has no identical partner with which to align: its closest match is the much larger X chromosome. Additionally, the X and the Y do not contain alleles of the same genes, so there is not much to swap. The only regions that do any meaningful exchange are the ones located at the very ends (telomeres) of the X and the Y, and they do not contain much useful information anyway. The remaining 95% of the Y chromosome does not recombine with the X chromosome.

Why is this genetic square dance so important? Arguably, the sole purpose of sexual reproduction is to allow the chance that a novel combination of alleles becomes superior to that of its parents in terms of survival and reproductive capability. Otherwise, we would just reproduce asexually, such as plants do when they give rise to shoots and buds. Asexual reproduction is far easier than sexual, but there is a cost: clones, being just like their parents, will live and die just like those parents, never improving the species. Furthermore, any environmental change may wipe out the entire species, since no individual members carry any different evolutionary changes to help them survive.

Back in the late 1990's, when the Y chromosome was being sequenced, it was discovered that much of that sequence is riddled with "junk" DNA, composed primarily of pseudogenes (dysfunctional genes) and other nonsensical or repetitive stretches of nucleotides. Over two-thirds of the Y chromosome is thought to be useless, the result of accumulated mutations which never had the ability to be exchanged for more useful genetic matter.

The consequences of this extensive non-functionality and non-exchange are grave: Y-bearing sperm often contain mutations, resulting in males who suffer from lifelong illnesses, sterility, or intersex conditions. One major player in this genetic landscape is a gene termed SRY (sex-determining region Y). SRY is required for testis development in the embryo; males born with a mutated copy of SRY range from being infertile to looking, at least physiologically, like females. Furthermore, SRY may go beyond determining maleness for the developing fetus: recently, researchers have discovered its possible role in Parkinson's Disease, schizophrenia, and addiction, conditions to which males are much more prone than females².

The size of the Y is another problem: due to it being very small, in comparison to its larger X partner, it is often lost during meiosis, the process wherein cells divide their genetic material in half to form sex cells. Sperm produced from cells which have no Y chromosome, or alternatively, both an X and a Y, result in individuals with Turner's Syndrome (XO) or Klinefelter's Syndrome (XXY), respectively. Compared to autosomal chromosomes, the Y chromosome is also more likely to break during its alignment with the X, resulting in a portion of the Y tagging along with the full X chromosome. Upon inclusion of this X/Y gene mixture into a sperm cell, the individuals resulting from fertilizations may look just like males despite being XX. This is especially true in cases where the full, unmutated SRY gene tags along with the X. Alternatively, depending upon the genes found within that Y fragment, these individuals may be hermaphroditic.

Male fertility has also evidenced a downward spiral with time: free radicals, higher chronological age of first-time fathers, and Y chromosome microdeletions have all been blamed on the decreased fertility of men, especially men living in industrialized countries. The influence of free radicals on fertility is well understood. For example, a man who smokes produces a far more mutagenic environment for his sperm compared with a non-smoking man. Because sperm are produced so quickly and in such mass quantities, and because their shells provide little protection against free radicals, it is understandable how this might occur. Similarly, with increased age, a man has been exposed to many more mutagenic events compared with his younger counterpart.³ However, infertility resulting from Y chromosome alterations does not always follow the obvious: around 5-15% men with severe infertility have an accelerated rate of Y chromosome degradation, regardless of age or exposure to environmental toxins⁴. It's as if these men are on an accelerated evolutionary path to oblivion, marked by an overtly degrading Y. Could mankind (and thus humankind) be on a similar, if slightly more slow, path to equal oblivion? And how did this all start anyway?

Evolutionary evidence indicates that at one time the X and the Y chromosomes were recombining autosomes. Around 300 million years ago, sex determination via DNA occurred with the acquisition of the SRY gene on one of those chromosomes⁵. The SRY-containing chromosome became the Y chromosome and its SRY-deficient mate became the X chromosome. Due to the necessity of maintaining this SRY gene in order to produce males, recombination between the two chromosomes lessened. The lack of recombination spilled over into neighboring regions, resulting in their genetic divergence as well. Increasing genetic dissimilarity also led to Y chromosome shrinkage, in order to minimize the chances that deleterious mutations would accumulate in the chromosome. Over time, larger and larger chunks of DNA decayed and were halted from recombining. Presently, only 5% of the Y chromosome mingles with its partner.

Given the current status of the Y, what could be its possible future? Some researchers argue that, while the original Y chromosome contained around 1,500 genes some 300 million years ago, the current version contains only 5% of that number, or about 78 genes (discovered after full sequencing of the Y). At this rate of decay, the Y chromosome may cease to exist in about 10 million years.⁶

Would this mean the end of men? Not necessarily. One other species has narrowly escaped its own genetically pre-determined extinction: the mole vole, whose Y chromosome has been completely obliterated from the genome. This animal exists as two separate species: one containing just a single unpaired X, and the other containing two X chromosomes. Males are still produced: the mole vole's SRY equivalent may simply reside on another chromosome (possibly to become the new Y). Alternatively, downstream genes, which used to be controlled by the SRY, may be scattered throughout the entire genome of the animal and activated in different ways, making the SRY irrelevant to maleness.

Humankind could adapt similarly, resulting in two (or more) such species, which would be incapable of breeding with each other due to chromosome number differences. Such a development would be astounding, with humans not being separate species since both Neanderthals and Homo sapiens roamed the earth.

Not all scientists share the same pessimistic view of men's future. The Y chromosome has been found to contain long stretches of palindromic DNA, which are like mirror images of specific genetic sequences. Quite often, such palindromes occur in pairs, leading to the hypothesis that the Y chromosome may actually recombine DNA within itself.⁷ If such recombination occurs, then it could help preserve Y chromosome integrity, stabilizing it against further genetic loss.

Sources:

1. Ensembl release 44: Homo sapiens Ovreview of Chromosome Y. http://www.ensembl.org/Homo_sapiens/mapview?chr=Y
2. Dewing, P; Chiang CW, Sinchak K, Sim H, Fernagut PO, Kelly S, Chesselet MF, Micevych PE, Albrecht KH, Harley VR, Vilain E (Feb 21 2006). "Direct regulation of adult brain function by the male-specific factor SRY". Current Biology 16 (4): 415-20.
3. The Y chromosome has fallen on some tough times http://www.signonsandiego.com/news/science/20030312-9999_mz1c12y.html
4. Battle of the Sexes> Save the Male http://www.channel4.com/science/microsites/B/battle_sexes/savethemale.html
5. Research looks at what drove sex chromosomes apart http://chronicle.uchicago.edu/991118/chromosomes.shtml
6. Human spermatozoa: The future of sex. R. John Aitken and Jennifer A. Marshall Graves. Nature 415, 963 (28 February 2002).
7. Finished Y-Chromosome Sequence Reveals a Genomic "Crystal Palace" http://www.hhmi.org/news/page5.html