Why the Y? Why is it important?

07/11/2018 by Campion Fund


The Y chromosome emerged at least 180 million years ago, some say 300 million years ago.  It evolved in a slow-step-wise fashion from autosomes along with the X. Over eons the Y chromosome became smaller than the X, a process that became known as Y degeneration. During its evolution the Y genes underwent a process of reordering their location on the chromosome compared to where they were on the proto- Y chromosome. The sex chromosomes allow for a greater genetic diversity in offspring as opposed to reproduction by cell-division in which a daughter cell contained the exact same genes as the parent.  Sexual reproduction which occurs when a male reproductive cell and a female reproductive cell meet and join allows for greater exchange of genes and thus enables every individual to be unique.  (Unless the individuals are identical twins, but that is another story).  Because sexual reproduction evolved, plants, animals and humans have thousands and thousands of individual traits that allow all the numerous and diverse species to develop that make our world vibrant and special.  The Y chromosome is vital for testis determination and for spermatogenesis in an adult. Spermatogenesis is an elegant biological process that begins with mitotic cell division (a process which allows each cell to have 46 chromosomes) of spermatogonia to give rise to primary spermatocytes that then in turn divide during meiosis (a process where each cell only has 23 chromosomes) to form secondary spermatocytes. Meiosis has to happen otherwise when one spermatozoa and an egg meet the offspring would have too many chromosomes. In fact, without meiosis the number of chromosomes will double with each generation. During this process genes can be exchanged by crossing over to another chromosome that is homologous with it. The secondary spermatocyte under goes a second meiosis to produce haploid round spermatids which go on to produce elongated spermatids and finally mature spermatozoa.  Hormones, local secretory factors and testis-specific genes contribute to this process as well.

The human SRY (Sex- determining region of the Y) is essential for the development of maleness in the embryo as it supports the differentiation of the bi-potential gonad into a testis.  It was first described in the 1990s and is located on the short arm of the Y chromosome (Yp).  In rare situations a subset of 46XX individuals are phenotypically male because the SRY region is translocated to the X chromosome.  This fact really shows that SRY is a male determining gene.

The long arm of the Y (Yq) contains many palindromes (symmetrical arrays of continuous repeats of long DNA sequences that point in opposite directions and are joined by a “spacer segment”) and amplicons (high-order organization of palindromes).  95 % of the Y chromosome is designated MSY (Male specific region) and does not recombine with a partner chromosome during meiosis. It does not recombine with other Y genes on another Y since most individuals have only one Y.  The palindromes and amplicons, however, made it easy for self-recombination to occur during spermatogenesis and enabled many intra-chromosomal deletions.  However, there are regions of the Y at the tips of the arms called PAR1 and PAR2 (pseudoautosomal regions) which consists of nucleotides that are homologous to pseudoatuosomal region on the X chromosome and can pair and recombine with them during meiosis. But these genes are not inherited in a strictly sex-linked manner. Some of the genes on the long arm are regulatory genes that are essential for life and have homologues on the X chromosome.

The long arm of the Y contains a region known as AZF (Azoospermic Factor).  Intra-chromosomal microdeletions in AZFa, AZFb, AZFc are known to cause male infertility.  It is estimated that the world-wide prevalence of Yq microdeletions is about 7.5% in infertile men, with the highest prevalence in Americans and East Asians. The microdeletions are transmitted to 100% of male offspring and are also associated with testicular cancer and neuro-psychiatric conditions.  Other Y genes have been reported to cause male infertility but they are uncommon.

For many years many genes on the Y were thought to be inert.  One writer called most of the Y to be a “functional wasteland”.  Now we know more about the Y genes and they are becoming increasingly important to male health as well as important in reproduction. The Y contributes to  complex traits and in males is a determinant of male autoimmunity.  A recent study has reported that men in the haplogroup I of Europeans have an increased incidence of coronary artery disease.   The reason cited is very interesting. Downregulation of genes found on the Y chromosome that have to do with antigen processing and presentation along with an up-regulation of Y genes in the inflammatory pathways and leukocyte migration combine to cause a significant inflammatory response and contribute greatly to atherosclerosis of blood vessels.  Therefore, study of other Y gene in the MSY regions are to be encouraged and may lead to other disease susceptibility genes.  The Y may not be so “inert” after all.  In summary, the Y is important in sex differentiation, in the development of the testis, in spermatogenesis and most likely plays an important role in the long-term health of men.  To learn more about the Y see the reading list below.

Further reading:

Colaco S, Modi D, Genetics of the human Y chromosome and its association with male infertility. Reproductive Biology and Endocrinology. 2018: 16: 14 do: 10.1186 Evolution of the Y Chromosome. ThIS IS A PART OF The Meaning of Sex: Genes and Gender

Hughes JF, Page DC. The biology and evolution of mammalian y chromosome. Annual Review of Genetics. 2015: 49: 507-527.

Maan AA.  The Y chromosome: a blueprint for men’s health. European Journal of Human Genetics: 2017. 11: 1181-1188.


Phyllis Leppert, MD, PhD