The total sequence of the Y was not discovered until 2022 (1). That study showed that the size of the Y varies among individuals and provided information regarding new genes. The Y chromosome is a small chromosome, only about one-third the size of the X. It is pivotal for male sexual development in humans ( and many other species of animals as well as some plants). Genes on other chromosomes play a part in male sex development, therefore it is essential to understand that the Y chromosome is not the only one that defines male sex characteristics. Typically, a father provides either a Y to sons or in the case of daughters a X. The Y chromosome does not contain many genes compared to other chromosomes. About 107 of the genes on the Y encode for proteins, but because a number of these genes are repeated, the numbers of “exclusive “ protein coding genes is about 42. The Y chromosome was first reported in 1905. However, it was not until 1920 that the scientific community discovered that the Y chromosome is a sexually determinant gene. Because the X chromosome was discovered before the Y the chromosome determining male sex was named Y as Y is the letter that follows X in the alphabet. The names of these chromosomes have nothing to do with their shape because chromosomes in cells unless undergoing mitosis are seen microscopically as a blob. The Y chromosome is thought to have evolved around 300,000 years ago. About 60% of the Y chromosome consists of repetitive DNA. This repetitive DNA consists of palindromes (the DNA base sequences read the same backwards or forwards), tandem repeats (2 or more DNA sequences repeated head to tail numerous times) and segmented duplications ( large DNA sequences that are repeated in a chromosome, either in tandem or interspersed). While autosomes undergo recombination with their autosome pairs, the Y chromosome cannot recombine with the X except in a very small part of the chromosome, the PARS or pseudoautosomal region located at the ends of the chromosome near the telomeres. A region called the NRY of non-recombining region is the male-specific region. A gene called SRY in this region causes the embryo to develop a testis. If the SRY gene does not code its protein or produce a functional protein the embryo will not develop a testis. Interestingly, the NRY region genes, SNPs (single nucleotide polymorphisms) are used by scientists interested in determining direct ancestral lines. Another important gene in this region is AZF which influences that number of sperm produced in the testis of a mature adult. Deletions in this gene is a known cause of male infertility. Other genes on the Y chromosome can be used by archeologists to determine the sex of human skeletal remains, especially in situations where only partial skeletal remains are excavated. A list of all the genes of the Y chromosome can be found on the National Human Genome Research Institute website (2). Sex determination is not always typical, however. “Biological sex” is both genotype and a phenotype. At birth it is the phenotype that parents and those who have attended the birth observe when they proclaim: “It’s a boy” or “It’s a girl”. There are situations when the Y chromosome, (the genotype), does not correlate with the physical appearance of a newborn, (the phenotype). These situations have demonstrated the complexities of sex determination and development in the human embryo. One of these situations is 46XY androgen insensitivity. This occurs when the individual has an alteration in a gene that binds a male hormone, androgen to cells. Thus, the individual affected has a male genotype, XY but a female phenotype. Occurring in 2-5/100,000 newborns, the child is raised as a female. They have a testis that is in the abdominal cavity, and a short vagina but no uterus. Although many are happily married to men, they are infertile. This situation can be even more complex, as the individual might display a mild expression of the phenotype. 46XX testicular sex development is a condition where the SRY gene is translocated to the X Chromosome. Therefore, an XX individual has a female genotype and a male phenotype, born with male genitalia. The testis is small and does not produce sperm. 1 in 20,000 newborns are affected and because they have a male phenotype at birth are raised a male. This situation can present as variations in the phenotype demonstrating the complexities of embryonic sexual development. 47XXY individuals develop a male phenotype and are able to father children. Often taller than others they generally have delayed development and learning as well as social and emotional disabilities. This situation occurs in 1/1000 births. 48XXYY individuals are born with a male phenotype. These individuals have small testis and decreased testosterone. They are often very tall and exhibit developmental and behavior issues and have impaired intellect. They are infertile. It is thought that the presence of two XX chromosomes interferes with embryonic sexual development. Persons with these conditions of altered sexual genotypes with atypical phenotypes deserve to lead the life that suits them and allows them to thrive. In many human cultures they are accepted for who they are as themselves. Human development is unique to every individual and persons with atypical genotypes/ phenotypes deserved to be treated with respect. These conditions are discussed in this blog to remind us that each life is complex and unique. As science discovers more about the Y chromosome, ideas of what is “typical” sex differentiation evolves. In the future, scientists will uncover more information. References
(1) Rhie A, Nurk S, Cechova M, Hoyt SJ, Taylor DJ, Altemose N, Hook PW, Koren S, Rautiainen M, Alexandrov IA, Allen J, Asri M, Bzikadze AV, Chen NC, Chin CS, Diekhans M, Flicek P, Formenti G, Fungtammasan A, Garcia Giron C, Garrison E, Gershman A, Gerton JL, Grady PGS, Guarracino A, Haggerty L, Halabian R, Hansen NF, Harris R, Hartley GA, Harvey WT, Haukness M, Heinz J, Hourlier T, Hubley RM, Hunt SE, Hwang S, Jain M, Kesharwani RK, Lewis AP, Li H, Logsdon GA, Lucas JK, Makalowski W, Markovic C, Martin FJ, Mc Cartney AM, McCoy RC, McDaniel J, McNulty BM, Medvedev P, Mikheenko A, Munson KM, Murphy TD, Olsen HE, Olson ND, Paulin LF, Porubsky D, Potapova T, Ryabov F, Salzberg SL, Sauria MEG, Sedlazeck FJ, Shafin K, Shepelev VA, Shumate A, Storer JM, Surapaneni L, Taravella Oill AM, Thibaud-Nissen F, Timp W, Tomaszkiewicz M, Vollger MR, Walenz BP, Watwood AC, Weissensteiner MH, Wenger AM, Wilson MA, Zarate S, Zhu Y, Zook JM, Eichler EE, O'Neill RJ, Schatz MC, Miga KH, Makova KD, Phillippy AM. The complete sequence of a human Y chromosome. Nature. 2023 Sep;621(7978):344-354. doi: 10.1038/s41586-023-06457-y. Epub 2023 Aug 23. PMID: 37612512; PMCID: PMC10752217.