This article is part of a fortnightly column exploring contemporary concepts and issues in genetics.
The Y chromosome, often referred to as the “master of maleness”, has long captivated scientists and historians alike. In humans, in addition to the 22 pairs of chromosomes in each, we have a pair of sex chromosomes called X and Y. Sex as a specification is determined by these sex chromosomes. They carry sex-determining genes. All biological males have X and Y chromosomes and all biological females have two X chromosomes. The ‘sex-determining region Y’ on the Y chromosome determines the biological male sex.
How is the Y chromosome characterised?
Estimated to have emerged around 200-300 million years ago in a common ancestor of all mammals, the Y chromosome has had a unique genetic journey, and embedded within its DNA lies a remarkable tale of evolution. Scientists published the complete genetic sequence of the Y chromosome in 2003. This sequence provided an outline of 23 million bases of the 60 million or so bases that together make up the Y chromosome. In total, the chromosome encoded for only 55 genes and accounted for around 2% of the genetic material inside a cell.
Many researchers jokingly refer to the Y chromosome as the “juvenile delinquent” among chromosomes thanks to its abundance of repetitive sequences, poor functional utility (with a small number of genes), reluctance to socialise (i.e. recombine with other chromosomes), and a high proclivity to degenerate over the course of evolution.
Indeed, because it has little potential to recombine, the diminutive Y chromosome has been passed from father to son, carrying the legacy of generations. Scientists have extensively studied it to understand human migration and evolution. It has also fuelled countless debates, unravelled the mysteries of paternity, revealed genetic diversity, and illuminated the intricate tapestry of our shared past.
Why does the Y chromosome matter?
In a landmark genetic study, published in March 2003 in the American Journal of Human Genetics, researchers reported that around 0.5% of all the men in the world have inherited a Y chromosome from the Mongol emperor Genghis Khan or one of his descendants. While the Y chromosome has been at the centre of many scientific and social controversies involving sex determination and gender discrimination, we would be better off not underestimating its influence on other aspects of health as well.
In fact, contrary to initial assumptions that the chromosome is degenerating and shrinking over time, and possibly has little functional role, researchers have discovered of late that the Y chromosome possesses genes that are vital to biological functions, including those linked to ageing and lifespan regulation (recent studies have shed light on an intriguing connection between the human Y chromosome and longevity).
In the animal kingdom (including mammals), scientists have noticed substantial differences in lifespan between the sexes: the females tend to live longer than the males. This phenomenon has been attributed largely to the absence of a second Y chromosome in males, exposing the deleterious mutations in the X chromosome. It is also well known that men lose the Y chromosome (LoY) with age and that this is associated with a higher frequency of cancers, Alzheimer’s disease, and a shorter lifespan. This has been corroborated by studies on mice models that showed that LoY resulted in shorter lifespans and that older mice with LoY displayed significant memory deficiencies compared to younger mice.
However, a recent study in fruit flies from France’s National Centre for Scientific Research, published in the journal Nature Ecology and Evolution on June 12, attributed the longevity to the phenotypic sex of the animal rather than the presence of a Y chromosome. Phenotypic sex refers to an individual’s sex as deduced from their genitalia.
Do humans lose the Y chromosome?
Studies conducted by researchers at the University of Virginia School of Medicine, U.S., and Uppsala University, Sweden, together with others have shown that LoY in humans occurs with age and is associated with several debilitating medical conditions – a finding that has been validated in mice with LoY, resulting in weak heart muscles (cardiomyopathy), stretched or thickened heart tissue (fibrosis), and heart failure. Scientists corroborated these observations with association studies in large human cohorts, such as the UK Biobank.
Yet all is not in vain for the male members of the species: researchers have also found that the pathological effects observed on account of LoY in mice’s hearts could be negated by transforming growth factor β1-neutralising antibodies, suggesting a potential treatment for this medical condition in future.
In another paper published in the same journal, on June 2, researchers performed an analysis of 29 primate sex chromosomes and suggested that in the last 80 million years, there has been a rapid evolution of the Y chromosome. This is exemplified by the fact that the human Y chromosome is about one-third as big as the X chromosome. So, many animal species, including humans, have a genuine fear of losing the Y chromosome in the distant future.
What lies ahead?
In fact, this has already happened in some species, such as rodents, which have naturally lost their Y chromosome. Such animals provide us with models to understand the process of sex-chromosome turnover and a means to repurpose another chromosome (i.e. one of the autosomes) into a sex chromosome.
Further, the evolutionary path leading to the appearance of modern humans provides clues as to what could be in store for the Y chromosome. Genome sequences of the Neanderthals, an ancient relative of the modern human, harbour telltale signs of the replacement of the Y chromosome beginning from modern humans.
This suggests that such replacement is not new to the human lineage, and that it is quite possible that the Y chromosome may have to relinquish its coveted title of “master of maleness” to another chromosome in the times to come.
Sridhar Sivasubbu and Vinod Scaria are scientists at the CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB) . All opinions expressed are personal.
- Estimated to have emerged around 200-300 million years ago in a common ancestor of all mammals, the Y chromosome has had a unique genetic journey, and embedded within its DNA lies a remarkable tale of evolution. Scientists published the complete genetic sequence of the Y chromosome in 2003.
- Researchers have discovered of late that the Y chromosome possesses genes that are vital to biological functions, including those linked to ageing and lifespan regulation (recent studies have shed light on an intriguing connection between the human Y chromosome and longevity).
- In another paper published in the same journal, on June 2, researchers performed an analysis of 29 primate sex chromosomes and suggested that in the last 80 million years, there has been a rapid evolution of the Y chromosome.
