Summary: Sex reversal is not unusual in some animals, especially in invertebrates. As for the vertebrates, there are reptiles and fish that can have their sex reversed under certain circumstances. Sex reversal in these animals is often driven by environmental and social factors. But how about mammals and humans whose gonads are fully differentiated and thereby permanent by the time they reach adulthood…? Can they, too, undergo sex reversal without going through any artificial intrusions? If so, up to what extent…?
Sex reversal occurring in nature
In a biological context, sex reversal pertains to the phenomenon in which the sex (gonadal and secondary sexual characteristics) of an organism is altered from one gender to another. This is fairly common among invertebrates, like a number of free-living nematodes. Within a given population, they can alter their gender – from male to female and vice versa. Less-favourable environmental conditions drive them to their sex reversal.1 Slipper-shell snails (Crepidula, sessile molluscan species) males are also capable of turning into females. Initially as a male when young, it changes into a female when a male sits close.2 Certain vertebrates are capable of sex reversal, too. For example, in a group of goby fish, the loss of an alpha male causes the largest female in the group to assume the role.3
Genetic factors in mammalian sex reversal
In mammals, natural sex reversal is plausible, albeit genetically and during early gonadal development. It can occur even in humans but only among those with genetic tendencies. Our gonadal plasticity is so limited that our gonadal sex is determined not by social or environmental factors but essentially by the activity of the existing sex chromosomes. Typically, a male has one Y chromosome and one X chromosome; a female has two X chromosomes. Previously, people mistook the X chromosome as the sex-determiner. Proofs from subsequent studies, such as the discovery of the sex-determining region Y (SRY) gene normally located on the Y chromosome, debunked the notion. The SRY gene carries the code responsible for the synthesis of a protein that can initiate the development of the testes. If the SRY gene is dysfunctional or nonexistent the testes will not form. Hence, the protein it encodes for was named testis-determining factor (TDF). In 1991, scientists successfully incited sex reversal on a mouse when introduced with SRY gene while still an embryo. Although it was chromosomally female to begin with, it eventually grew male gonads.4 Thus, in spite of the minuscule size and having fewer genes than the X chromosome, the Y chromosome is considered the key to determining the chromosomal sex owing to its SRY gene.
(Read a related article on Y chromosome: Men could go extinct? Y chromosome is slowly disappearing)
Junk DNA Enh13 in sex reversal
A research team from the Francis Crick Institute found yet another chromosomal piece that resulted in gonadal sex reversal in mice. It contained genes that were regarded as junk. Junk DNAs are called as such because they are noncoding genetic material. In human genome, a meager 2% codes for the building blocks of proteins crucial to life. The remaining percentage, which comprises the bulk, is deemed unnecessary, and therefore, dubbed as junk. Apparently, they do not code for proteins. Nevertheless, recent findings suggest that they, too, play an important role. The enhancer 13 (Enh13) exemplifies it. The researchers found that the lack of Enh13 in male mice led to their sex reversal. Instead of testes, the mice grew ovaries and female genitalia. 4 This could mean that the junk DNA Enh13 takes a crucial role in early gonadal development. Enh13 supposedly enhanced the production of SOX9 protein. SOX9 gene encodes for the SOX9 protein. The SOX9 gene does so when TDF proteins bind to the enhancer sequence upstream of the SOX9 gene. The more SOX9 proteins produced the more that the embryo will commit to developing into a male.
Impact of Enh13 findings on sex reversal
Dr. Nitzan Gonen, one of the researchers on the team, talked about the impact of their study on mammalian sex reversal. He said that so far they identified four enhancer regions and they were surprised how a single enhancer could control “something as significant as sex”.4 Their Enh13 findings could be used as a genetic basis to understanding sex reversals in humans and other mammals.
Sex reversal in mammals occurs but is not as extensive as that in other animals. Gonadal plasticity is confined during the time of embryonic development. Upon reaching adulthood, the gonads are already formed and will not change from one type to another. When both male and female gonads develop (in the case of intersexuality), usually, only one of them, or none, will be functional. Sex reversal in humans has also been reported. One such example is the case of two brothers and a paternal uncle from the U.K. They are outwardly and anatomically males but genetically females (with 46, XX karyotype).5 Genetic mutations might have been the underlying cause. More studies on the molecular genetics of sex reversal could help provide insight as to the gender ambiguities in humans, which, unfortunately up to this day, have no clear genetic explanation.
— written by Maria Victoria Gonzaga
1 Kent, G. C. (2018). Animal reproductive system: sponges, coelenterates, flatworms, and aschelminths. Encyclopædia Britannica. Retrieved from https://www.britannica.com/science/animal-reproductive-system/Sponges-coelenterates-flatworms-and-aschelminths#ref606936
2 Smith, N. G. (1999). Reproductive behavior. Encyclopædia Britannica. Retrieved from https://www.britannica.com/science/reproductive-behaviour-zoology/Reproductive-behaviour-in-invertebrates#ref497554
3 Wilson, M. (2013). Sex-reversal in adult fish. The Company of Biologists. Retrieved from http://thenode.biologists.com/sex-reversal-in-adult-fish/research/
4 The Francis Crick Institute. (2018). Non-coding DNA changes the genitals you’re born with. ScienceDaily. Retrieved from www.sciencedaily.com/releases/2018/06/180614213729.htm
5 Cox, J. J., Willatt, L., Homfray, T., & Woods, C. G. (2011). A SOX9 Duplication and Familial 46, XX Developmental Testicular Disorder. N Engl J Med. 364 (1):91-93. doi: 10.1056/NEJMc1010311. Retrieved from https://www.nejm.org/doi/full/10.1056/NEJMc1010311
Hold on to your seats, gentlemen — the male chromosome (Y chromosome) is slowly disappearing at a relatively fast rate and it might be gone completely in the future. This presumption is based on the genetic studies on the Y chromosome. It used to be genetically the same as the X chromosome. However, it has degenerated gradually, and now, it shriveled and became less relevant.
Y chromosome as male-determiner
Humans have two types of sex chromosomes: the X chromosome and the Y chromosome. Females have two X chromosomes whereas males have only one. Nonetheless, males have the Y chromosome that is passed on across generations from fathers to sons. In the XX/XY sex-determination system, the Y chromosome is the male-determining sex chromosome. Previously, the X chromosome was regarded as the sex-determiner. This conjecture, however, was eventually proven wrong when the SRY (sex-determining region Y) gene was identified on the male chromosome.1 This gene codes for the testis-determining factor, a protein that triggers testis development. Without this gene, testis fails to develop in males. There are few other genes present on the Y chromosome. However, compared with the X chromosome, the Y chromosome is relatively gene poor and the only highly notable gene on it is the SRY gene.
The disappearing Y chromosome debate
Going back in time, about 166 million years ago, the first mammals had a Y chromosome (called a proto-Y chromosome) that was genetically similar to and of the same size as the X chromosome.2 However, the male chromosome diminished into the short Y chromosome that it is now. The Y chromosome degenerates as it loses genes through time. Unlike the other chromosomes, the Y chromosome does not undergo genetic recombination. Based on the current speed of degeneration, the Y chromosome would likely have 4.6 million years left, which relatively speaking is not that long, considering the 3.5 billion years that life has existed on Earth.2 Some mammals, such as certain rodent species, have already lost their entire Y chromosome. 3 Some experts (referred to as the “leavers”) infer that this event would also happen to humans in the future. This notion was opposed by others (the “remainers”) who believe that the Y chromosome would not disappear completely because it has evolved corrective mechanisms that slow down and deter gene loss. Gene amplification (the acquisition of multiple gene copies) and the presence of palindromes (a sequence that reads the same, whether backward or forward, e.g. AGTGA) help mitigate gene loss.3
Men without Y chromosome in the future
If the Y chromosome ultimately disappears in the future, what will happen to men? Will there be men in the future? Experts believe that men will get by when that time comes. Men would still be around just as women have been perfectly fine without the Y chromosome. As for the SRY gene, it could move to a different chromosome. Nonetheless, the chromosome that would take this gene would be at risk of going through the same fate as that of the Y chromosome.3 The absence of SRY gene on the male chromosome is not new, however. In Swyer syndrome, the individual has a Y chromosome lacking the SRY gene and consequently fails to develop testis and other internal male organs. A person with this genetic condition is outwardly female but with a karyotype of a male (i.e. XY karyotype) .2
Further research on the degenerating male chromosome is essential to monitor the rate of gene loss on Y chromosome. One possible implication of the possible complete disappearance of Y chromosome is the impending necessity for more advanced reproductive modalities that can be applied artificially not just on humans but also on other mammals as reproduction by that time would ever hardly become natural.
— written by Maria Victoria Gonzaga
1 “Y chromosome”. (n.d.). Biology-Online.org Dictionary. Retrieved from [https://biology-online.org/dictionary/Y_chromosome].
2 Griffin, D. & Ellis, P. (2018). The Y chromosome is disappearing – so what will happen to men?
Retrieved from https://theconversation.com/the-y-chromosome-is-disappearing-so-what-will-happen-to-men-90125
3 Griffin, D.K. Is the Y chromosome disappearing?—Both sides of the argument. Chromosome Res (2012) 20: 35. https://doi.org/10.1007/s10577-011-9252-1