The Disappearing Y Chromosome

The Disappearing Y Chromosome

 The size of the human Y chromosome is only a fraction of what it used to be. Once it was homologous to the X chromosome, but it now contains only 45 out of the 1700 genes it used to have[1]. Based on previous studies and assuming a linear rate of decay, it is expected that the human Y chromosome will disappear in roughly 4.6 million years.

 Does this mean the end of males? Not quite.

 A degenerating sex chromosome seems to be the norm of genetically determined sex[2]. In fact, organisms exist where the male chromosome is completely lacking, supporting the theory of the disappearing Y chromosome[2]. However, a study conducted by Hughes et al. provides new evidence on why the Y chromosome to stay for much, much longer.

 The male specific region of the Y chromosome (MSY) is not capable of genetic recombination with the X chromosome. Without genetic recombination, there are fewer mechanisms for genetic repair, leading to higher rates of mutations, deletions and insertions, all this, pointing to the inevitable degeneration of the Y chromosome.

 Hughes et al. argues that the human Y chromosome has reached stability, where it will not degrade further, by sequencing the genomes of the rhesus macaque and comparing it to that of the chimpanzee and human genome. The study focused on the MSY, identifying five distinct regions or “strata” based on its degree of similarity to the X chromosome.

 Comparison between the macaque MSY and the human MSY revealed that they share the same 18 ancestral genes in strata 1 to 4, indicating that their last common ancestor shared the same genes and that there was no subsequent loss of these genes after the human and macaque lineages diverged 25 million years ago. In strata 5 all species showed significant gene loss, losing 5 ancestral genes (4 for macaque) over the past 30 million years. However, the same genes are found on the human and chimpanzee MSY, indicating that this region has stabilised prior to the human/chimpanzee split.



 The findings of this study contradict the linear model for the degeneration of the Y chromosome as they fail to explain the relative stability of the human MSY genes over the past 25 million years. The results suggest an exponential decay with a baseline constant which extends the lifespan of the human Y chromosome indefinitely into the future.

The Y chromosome isn’t going anywhere… at least for a while

The Y chromosome isn’t going anywhere… at least for a while


Opposing the popular theory about the gradual mutation of the “Y” chromosome in the human male, scientists from the Whitehead Institute for Biomedical Research in Massachusetts have reportedly confirmed that the chromosome's genes are very unlikely to change for at least several million years. Hundreds of millions of years ago, the “X” and “Y” chromosomes in the human genetic makeup matched up very smoothly; in much the same way as the other 22 autosomal chromosome pairs in humans still do to this day.

Originally, the two human sex chromosomes exchanged genes as was necessary for appropriate gene repair, which effectively avoided many serious mutations in the DNA. Approximately 166 million years ago, however, a sizable portion “Y” chromosome was turned around and incorrectly inserted into one mammalian ancestor of humanity, which changed the very shape of the chromosome, giving it the characteristic “Y”-shape that it now possesses. This serious mutation rendered the human sex chromosomes incapable of trading genes, and this was inherited to the next generation. Previously, scientists had accepted the fact this genetic anomaly would result in the gradual elimination of the Y chromosome, leaving the male gender with an “X0” chromosome pair, which is more simply an “X” chromosome not attached to anything else (Hughes, et al, 2012).

Chromosomes reside within cellular genetic material. In a human somatic cell, there are normally 46 chromosomes existing as homologous pairs. In simple terms, a homologous pair is a couple of chromosomes with the same lengths, centromere positions and staining patterns (Reece, et al, 2012). In a homologous pair, both chromosomes possess identical genes for heritable characteristics. Human females carry a distinct homologous pair of sex chromosomes in their genetic makeup, often simply dubbed “XX” in reference to the overall shape of the chromosomes. Males do not possess homologous sex chromosomes, and instead carry one “X” and one “Y” chromosome. These two different chromosomes are only very slightly homologous, which was the primary source of the initial theory that the “Y” chromosome may, in due time, disappear as a genetic mutation (Hamzelou, 2012).

Homologous chromosomes, including the Y chromosome.
Dr Jennifer Hughes, the head scientist of the team at the research institute, has ultimately proven that this is not the case. It has been stated that although the “Y” chromosome did indeed lose a substantial amount of its original genes at the time of the first known mutation, there has no been no change in the remaining genes since. Hughes infers that these genes serve highly specific, vital functions in the body, which suggests that there is great doubt that any noticeable alterations to this chromosome will take place, at least for many million years. Currently, little has been confirmed regarding why this genetic anomaly first came about, although, naturally, several theories do exist. Upon comparing the human genome to that of the rhesus macaque, a primate species of which human evolutionary ancestry can be traced back approximately 25 million years, Dr Hughes was able to confirm that males of both species retained the exact same percentage of genes in the “Y” chromosome. This genetic breakthrough was able to prove that after 25 million years, there was no further deterioration since the first known anomaly in the “Y” chromosome, thus disproving the idea that, in time, the “Y” chromosome would cease to exist.

Junk DNA

Junk DNA

In 1953 Watson and Crick were the first to discover the 3 dimensional helix shape that we now know is DNA. They determined the role of DNA is to transfer heritable features from one generation to the next.  (Campbell, et al. 2009) However within DNA there is a section they called Junk DNA.  This is an area of non-coding nucleic acids called introns. (Campbell, et al. 2009)
Initially Watson and Crick thought the Junk DNA had no real use and dismissed it as non-coding proteins.  However scientists now believe that the non-coding DNA that makes up 95-98% of the human genome has a much more important role than originally thought.

In recent years more and more research is being performed investigating the real role of the junk DNA and these findings are conflicting with original assumptions.  In 2010 scientist set out to explore the relationship between a non-coding stretch of chromosome (9p21) and heart disease. They said that individuals with a nucleotide mutation along this stretch of DNA are at greater risk of suffering from the disease.  The non-coding stretch of DNA was deleted in a group of mice. The results showed the mice that had the DNA deleted actually died earlier or developed tumours when compared with mice that had the stretch of DNA intact.  They concluded that the genes that may have been deleted on the stretch of DNA may control or ultimately inhibit cell proliferation in heart and other tissues. Meaning that without these genes, cells in arteries divide faster which build up causing restriction of blood flow to the heart which causes heart disease. (Visel et al, 2010)



Another idea of the possible functions Junk DNA performs comes from research done on the genomes of fruit flies. The genome of the fruit fly is approximately 80% junk DNA and it seems that the rate in which the flies DNA mutates is far less than what was expected. This means that because of no mutations the evolution of the fly has effectively come to a halt. Furthermore, they go on to say humans and mice have similar genomes, each consisting of around 30,000 genes.  However the species are hugely different. They think that it’s not the genes that separate the species but in fact the junk DNA. Humans have one of the largest proportions of junk DNA out of all species. This may explain the complexity of our species. (Andolfatto, P.  2005)

From recent research it seems to be emerging the idea that junk DNA plays a more important role in human existence than first thought. Whether or not experiments on animals can be applied to humans is yet to be seen. The nature of this type of work has many ethical issues and may take years until experiments on humans are possible. Could it be that one day junk DNA will be considered no longer trash and instead treasure? Only time will tell.

Human and dolphin genomes

Human and dolphin genomes

Humans and dolphins, what do these two animals have in common? You might think that the only thing they could have in common is that they are both mammals. You’re right, but there is a much more interesting fact. Dolphin and human genomes are almost the same. Dr. David Busbee from the Texas A&M University has been involved in a project that studies the genome of dolphins (Kolber, 2010). His team did a number of experiments using hybrid chromosomes combining human and dolphin chromosomes to identify the homologous traits. The results showed that 36 blocks were matching on both species (Fig.1&2). The experiment consisted in “painting” the chromosomes with a fluorescent chemical that would show the homologous traits (Fig.3). Busbee said that he was very surprised when he got to see the results. Because dolphins seem so different animals compared to humans, they live in oceans, eat fish and their physiology is far from ours. However, scientists believe that at some point humans and dolphins came from the same branch of the evolutionary tree. This is shown by the fact that dolphins are mammals that breathe air just like us, so it is believed that initially they were living on land and moved back to the oceans at a later time.

Fig1: Homologies between human and dolphin chromosomes detected by chromosome painting

Fig.2: Matrix showing the distribution of conserved chromosome segments between dolphin  and human

 


Fig.3: Painting of dolphin chromosomes with biotinylates human chromosome-specific paints. Yellow are matching traits.

But how is this discovery useful to science and to us? Evans (2010) discussed that because dolphins have such similarity, they are affected by the same toxins and diseases that affect us. For example, they are affected by red tide toxins, chemicals that are present in wastes which we dump in the sea and other toxins that are present in ocean life. Furthermore, not only have dolphins been affected by the same toxins but they also have learned how to fight or block the effects of these dangerous chemicals. So in other words, if we were able to find out how they are able to have immunization to what affects us, we could use this information to cure or fight the diseases that are caused in humans! For example, we could synthetize a vaccine for diseases. Another important fact is that dolphins can fight type 2 diabetes by simply “switching off” the gene that is affected by the illness and so block the effects of it (Gill, 2010). That would mean that we could cure thousands of people much faster. Another way in which this discovery could help science is that scientists have been studying the dolphin’s genome for years, but with little progress because of lack of resources. But with knowing that it is so similar to our genome it would speed up research by up to 20 years! That would save up a lot of time and money.

Chromosome mutations in yeast cells caused by stress

Chromosome mutations in yeast cells caused by stress

When we consider the concept of evolution, we think of genetic changes in a population over time – perhaps over hundreds or thousands of years. However, some organisms appear to have the ability to genetically evolve in just a few days by inducing chromosome mutations in response to stressful conditions. This phenomenon was studied by a team from the Stowers Institute for Medical Research in 2011. By examining the effects of several stressors, including heat and extreme chemical concentrations, they found that chromosomal variations and consequent drug resistance is the result of the action of heat-shock protein 90 (Hsp90).

In the experiment, yeast cells were submitted to high and low concentrations of a variety of chemicals for 12 to 14 hours. Then, the number of colonies of yeast cells that had an uneven number of chromosomes was compared with the number of colonies with the normal number of chromosomes. Many different stress factors increased chromosomal instability in yeast cells. Most significantly, the result of exposing yeast cells to the drug radicicol, even at a low concentration, was a chromosome loss rate about 300 times higher than the control in stress-free conditions. Exposure to a temperature of 50.9°C produced a similar result.

Graph displaying effects of stress conditions on frequency of colonies that are missing chromosomes

Images displaying effects of stress conditions; red colonies have chromosomal abnormalities

The reason for this surprising result is that radicicol binds to the Hsp90 molecule and disrupts its performance and heat also inhibits the protein. Hsp90 aids the correct duplication of chromosomes during cell division so that the daughter cells contain the same number of chromosomes as the parent cell.When Hsp90 is inhibited, replicated cells are more likely to demonstrate aneuploidy, meaning that they are missing or have an extra copy of a single chromosome.

The genetically diverse colonies of yeast produced by radicicol treatment were then exposed to several different drugs and their performance compared to control colonies. The results showed that the survival rates of the radicicol-treated colonies were much higher against all three drugs.


Images displaying comparison of control yeast colonies and radicicol-treated yeast colonies after exposure to drugs

So how does genetic diversity give a population such an advantage when it comes to survival? Genes within chromosomes determine which proteins are produced in a cell. The number of copies of a gene present in a cell may influence the expression of the gene and thus the final physical characteristics of the organism.For example, four of the yeast colonies that survived exposure to fluconazole demonstrated aneuploidy by containing an extra copy of chromosome 8, and by consequence, an extra copy of the ERG11 gene.This gene helps make organisms more resistant to fluconazole, which normally causes damage to the cell wall of fungal cells.


While the study helps explain one of the mechanisms that make some strains of yeast cells drug resistant, it could be useful in predicting the response of cancer cells to certain treatment. The researchers highlighted similarities between yeast and cancer cells, which often have unusual numbers of chromosomes. This is significant because, previously, some drugs were thought to be able to fight cancer by inhibiting Hsp90 and damaging protein production in the cancer cells.However, these drugs may actually produce drug-resistant cancer cells instead of treating cancer.