The mysteriously evolving Y chromosome…
Posted by on January 18, 2010 - 8:52am

I know what you’re thinking, this is a Women’s Health Blog - but we like men here too.  A recent study published in Nature (and featured in the New York Times) reveals some interesting new insight into the X-chromosome’s somewhat puny-looking counterpart.  Researchers Jennifer Hughes and David Page at the Whitehead Institute have discovered that the Y-chromosome appears to be evolving much faster than the rest of the genome.

Humans have 23 pairs of chromosomes (46 total); two of those chromosomes, called the sex chromosomes, are responsible for determining the sex of a human. Women have two of the same chromosomes, named X (see “What’s with the dancing X chromosomes?"), while men have one X chromosome and one Y chromosome, thus resulting in a mismatched pair.  Scientists have known for quite some time that the Y chromosome originally contained the same genes as the X chromosome, but has lost most of those genes through evolution.  Because of this, scientists have believed that the Y chromosome has been degrading through gene loss and has reached, or will reach a static state.

This new research however may prove otherwise.  In their study, Drs. Page and Hughes compared the genetic makeup of the human and the chimp.  Since chimps and humans shared a common ancestor just six million years ago, the differences in the genomes can help determine rates of evolution in the species.  The researchers found that while the chimp and human genomes differed in less than 1 percent of their DNA, comparison of the Y-chromosomes shows a difference of 30%.  This data indicates that this chromosome in particular is not static, but is in fact evolving at a greater rate than the rest of the genome.

The researchers suggest that some of this rapid evolutionary diversity might be attributable to differences in the mating patterns of humans and chimps and the large role of genes on the Y chromosome in sperm production.  A unique feature of the Y chromosome is that because it occurs in a mismatched pair with the X chromosome, it cannot exchange genes (called crossing-over) prior to meiotic cell division the way that the other twenty-two chromosomes do.   This places increased selective pressure on the Y chromosome, since a change in one gene must affect the reproductive fitness of the others.  In addition, the structure of the Y chromosome provides it with the opportunity to exchange genes with itself, which could accelerate the rate of change in its genetic sequence.

So does this mean that men are evolving faster than women?  No it doesn’t (sorry guys).  However, according to Andrew Clark, a geneticist at Cornell University (see NYT article), the rapid changes of the Y chromosome could have broader effects on the rest of the human genome.  Only further research will tell…

Science Mini-Lesson: X chromosome inactivation
Posted by on October 21, 2009 - 10:00am
Image: Indigo Instruments

Image: Indigo Instruments

In a recent post called, "Autoimmunity and Gender", we mentioned that one reason women are more prone to autoimmune disorders, or those conditions where the body's immune system attacks its own cells, is because of chromosomal influence, but we didn't elaborate. If you're guessing that it has something to do with the sex chromosomes, the X and Y, you are totally correct...but it may not be for the reason you think. It is not merely the presence of the two X chromosomes in genetic females that leads to autoimmune disorders, but the way the body handles them.

Genetic females have two X chromosomes while genetic males have one X and one Y, so females have twice as many X genes as males, right? Wrong! The X chromosome is incredibly rich in genes that are then made into proteins, while the Y has significantly fewer important genes. Fortunately, the body recognizes this potentially harmful difference in gene number and corrects the problem by a process called X-chromosome inactivation. In this process, every cell in the body chooses one X chromosome, either the one inherited from the mother or the one from the father, to make inactive. That DNA in that chosen chromosome is then wound up very very tightly to form what is called a barr body. Because it is wound up so very tightly (a formation called heterochromatin), the genes from the barr body can not be made into proteins, so it is considered inactive.

If genetic females have one active X chromosome, and so do males, how does this influence the risk of autoimmune disorders? Well, remember that every cell chooses which X chromosome to inactivate and that they do this independently of each other. One heart cell may inactive the X chromosome from the mother, while another right beside it inactivates the X chromosome inherited from the father. This makes all genetic females a type of genetic mosaic: our cells can express two different sets of chromosomes depending on which X chromosome is inactivated.

Image: Haane-Mugaas.com

Image: Haane-Mugaas.com

Getting to the point, think about immune cells: they're these destroyer cells whose sole mission is to hunt down and kill any cells that don't match their DNA code. Usually, this is a good way to target the bacteria and viruses that don't belong, but the immune cells can also get a little too good at their job. If an immune cell that has inactivated the maternal X chromosome meets a nerve cell that has inactivated the paternal X chromosome, that immune cell could be triggerred to destroy the "invader." That, in the end, is how having two X chromosomes can lead to increased risk of autoimmune disorders in genetic females.

PS- Why the picture of the calico cat? Besides the fact that cats rule, fur color is also X linked and depends on X chromosome inactivation. One fur cell decides to inactivate the maternal X carrying orange color, so that cell (and all the cells that come from it) are black or white. Nearby, the opposite happens and you get a patch of orange fur from Mom's X chromosome staying active. It's science in action!

For more information:

What's with the dancing X chromosomes?
Posted by on August 4, 2009 - 10:42am

Trademarked logoHave you noticed the Institute for Women’s Health Research logo?

Our logo features two "dancing" X-chromosomes shaded in spring green - representing fresh approaches to conducting research, and purple to show our commitment to creating interdisciplinary research teams in search of breakthrough sex- and gender-specific research at NU, whose official color is purple.

Now, onto the lesson plan, the following is what you will read in a physiology textbook.....With the exception of egg and sperm cells (germline cells), each cell (somatic cells) in the human body contains 46 chromosomes. These 46 chromosomes are divided into 22 pairs of autosomes and 1 pair of sex chromosomes.  Autosomes contain genes that are responsible for the development of the human body; they give us characteristics such hair and eye color or blood type. Sex chromosomes determine genetic sex and are generally made up of two X chromosomes (XX) in women or an X and a Y chromosome (XY) in men. The sex chromosomes contain genes that are responsible for the development of internal and external sex organs.

What is not discussed in traditional physiology textbooks are the relatively newer scientific discoveries surrounding the fact that EVERY cell in your body has a sex (not just your egg or sperm cells). For instance, a pancreatic islet cell will contain 22 pairs of autosomes and an XY pair in a male, but in a female the pancreatic islet cell will contain 22 pairs of autosomes and an XX pair. In other words a pancreatic islet is not exactly the same in a female and a male. Genes on the sex chromosomes are expressed differently in males and females and therefore the sex of cells needs to be taken into account when we conduct scientfic research. Because of these basic molecular differences scientists are starting to uncover distinct health differences (beyond the reproductive system) between males and females. The incessant problem of the past is that most research has been conducted in males (XY) and then applied to both women and men with sometimes devastating effects to women. The Institute for Women's Health Research promotes scientific discoveries regarding the contribution of sex and gender to the overall experience of health and disease. Not only do we advocate for increased inclusion of females in research studies, we stress the importance of designing studies so they look specifically at sex and gender variables and that the results are reported appropriately to reflect any differences.