Notes on: A fresh look at the male-specific region of the human Y chromosome

Posted 2 January 2014 by M. Wilson Sayres

I think that it would be useful or me to take notes on the papers I'm reading, and I figured it might be useful to share them online because, open science and all. These papers will be in my area of study: sex chromosome evolution and sex-biased processes. If you're interested, please go read the paper, and we can have a discussion in the comments. The link to the paper and full citation are found at the bottom. Let's jump right in!

Jangravi et al. (2013) introduce the Chromosome-centric Human Proteome Project (C-HPP), focusing on the Y chromosome (Y-HPP). Their project is scheduled to run over the next 10 years, and they state that "the objective of Y-HPP is to map and annotate all proteins encoded by genes on the MSY sequences." In this, Jangravi et al. (2013) give an excellent overview of the Y chromosome, contribute new synthesis of previous work, and describe the plans for their group's project.

As background, the male specific region of the Y (MSY) is composed of three broad regions, originally described together by Skaletsky et al (2003):

X-degenerate region (relics of the ancestral sex chromosomes)
X-transposed region (transposed from the X to the Y after chimpanzee-human divergence)
Ampliconic region (repetitive region, mostly acquired from the autosomes)

In addition to the male-specific region, the human Y has two pseudoautosomal regions that are shared with the X chromosome. I'm still not sure about using images from papers in blog posts, so go here to see a schematic of the Y chromosome regions from Skaletsky et al. (2003).

Some notes from the paper:

There are 60 unique genes (loci) on the male-specific region (MSY) of the Y chromosome, but there is not yet reliable protein evidence for 20 of these. This means that, although the DNA sequence seems like it should make a functioning product, and we have evidence of transcripts for most of these, we have not yet observed whether a protein is made. Not making a protein doesn't necessarily mean the gene is non-functional.

"Of the MSY proteins, 16.0% do not have a known molecular function."

"The sub cellular localizations of 25.0% of proteins remains undescribed."

"About 15% of all XY sex-reversed individuals have been known to carry SRY mutations."

"...SRY causes differentiation of pre-Sertoli cells to produce a testis and suppress genes that favor the formation of the female gonad" starting at 7 weeks of development.

Sertoli cell-only syndrome, a condition characterized by the presence of complete Sertoli cells in the testes but a lack of spermatozoa in the ejaculate, results from mutations in DDX3Y and USP9Y. DDX3Y (an ATP-dependent RNA helicase) and USP9Y (encodes a protease with activity specific to ubiquitin and is involved in the regulation of protein metabolism (protein turnover)).

One in six prostate cancer specimens showed at least some Y chromosome-specific genes lost in most specimens. Especially interesting (to me) is that decreased (< 20) copy number of TSPY is associated with increased incidence of prostate cancer.

A database of protein interactions of Y-linked genes available in the PPI section of the Human Y chromosome Proteome Database: http://www.hupo.ir. This will be very useful, especially as they add more to it.

Post-translational modifications (modifications made to the protein that we cannot currently predict from the DNA sequence of the gene) are still poorly understood. For the Y-linked gene DDX3Y at least 67 post-translational modifications have been identified, falling into five types: phosphorylation, deamination, acetylation, ubiquitination, and methylation. I'm really curious what the effects of all of these are.

Cool. I am very excited to keep tabs on the results coming out of this project. For all that we have yet to understand about the genome, we have even more to understand about how genes actually function as proteins (and/or RNA).

2013 Jan 4;12(1):6-22. doi: 10.1021/pr300864k. Epub 2012 Dec 20.

A fresh look at the male-specific region of the human Y chromosome.

21 Comments

DS · 2 January 2014

X-degenerate region (relics of the ancestral sex chromosomes)
X-transposed region (transposed from the X to the Y after chimpanzee-human divergence)
Ampliconic region (repetitive region, mostly acquired from the autosomes)

It would be interesting to see how anyone who denies the common ancestry of humans and chimps would explain this organization of the Y chromosome. Most likely they will ignore it or make up some story about why the "designer" wanted to do it this way. Y remains a mystery to them.

M. Wilson Sayres · 2 January 2014

Agreed. The Y chromosome is an excellent example of evolution in action!

pngarrison · 3 January 2014

A recent paper indicates that at least some people have a third pseudoautosomal region (where recombination has happened) in an X-transposed segment on the Y. I have only seen the abstract.
http://www.ncbi.nlm.nih.gov/pubmed/23708688

DS · 3 January 2014

pngarrison said: A recent paper indicates that at least some people have a third pseudoautosomal region (where recombination has happened) in an X-transposed segment on the Y. I have only seen the abstract. http://www.ncbi.nlm.nih.gov/pubmed/23708688

Thanks for the reference. Looks like evolution of the Y chromosome continues.

M. Wilson Sayres · 3 January 2014

pngarrison said: A recent paper indicates that at least some people have a third pseudoautosomal region (where recombination has happened) in an X-transposed segment on the Y. I have only seen the abstract. http://www.ncbi.nlm.nih.gov/pubmed/23708688

The region their referring to is the X-transposed region, listed above. All human Y chromosomes have the X-transposed region, but it is not yet clear whether it recombines in all males.

Frank J · 5 January 2014

DS said: X-degenerate region (relics of the ancestral sex chromosomes) X-transposed region (transposed from the X to the Y after chimpanzee-human divergence) Ampliconic region (repetitive region, mostly acquired from the autosomes) It would be interesting to see how anyone who denies the common ancestry of humans and chimps would explain this organization of the Y chromosome. Most likely they will ignore it or make up some story about why the "designer" wanted to do it this way. Y remains a mystery to them.

Unfortunately they get away with that because too many of us let them. By "get away" I don't mean necessarily convince any fence-sitters "leaning toward evolution" to lean the other way. But merely to fool most nonscientists into thinking that common ancestry (by whatever mechanism) and "some designer did something at some time" are equivalent alternatives. So whenever they pull that trick, one must always mention that the formal equivalent is not what they pretend it to be, but rather that 2 lineages originated independently from nonliving matter (with or without designer intervention). Skilled anti-evolution activists nowadays know better than to specifically deny "common ancestry (by whatever mechanism)." Rather they might deny "macroevolution" (their own nonstandard definition), or be otherwise vague. That technically leaves the door open to the possibility of "in vivo" speciation that they would not consider "evolution." They're very unlikely to bring up that possibility, however, preferring keep the audience accepting the "evolution or Genesis" stereotype. Regardless of the denier's rhetorical skill, this is always an opportunity to demand that they clearly state their alternate explanation, i.e., does it require 2 or more origin-of-life events, and when they think those events (or only one if they so admit) occurred. Non-skilled evolution-deniers will be caught off guard with such unexpected questions, but even skilled ones will show all but the most hopelessly compartmentalized members of the audience that they refuse to play on a level playing field. Or as I often say, they "expel themselves." They'll do anything they can to take the focus off of their alternate "theory" and back to "weaknesses" of "Darwinism."

Bobsie · 5 January 2014

I may have misunderstood but I've heard that for birds, the XY chromosome is female and XX is male. Does the Y-HPP study have anything to say about the Bird sex chromosome?

M. Wilson Sayres · 5 January 2014

Bobsie said: I may have misunderstood but I've heard that for birds, the XY chromosome is female and XX is male. Does the Y-HPP study have anything to say about the Bird sex chromosome?

In birds, ZW individuals are females and ZZ are males. This Y project will likely not have anything to say about birds. They'll have their hands full just figuring out what all the proteins on the Y chromosome do, where, and when!

John Harshman · 6 January 2014

Bobsie said: I may have misunderstood but I've heard that for birds, the XY chromosome is female and XX is male. Does the Y-HPP study have anything to say about the Bird sex chromosome?

There are a number of systems for sex determination in animals. When the male sex chromosomes are different, we conventionally call them X and Y, even though those chromosomes in various different groups aren't homologous. When the female sex chromosomes are different, we conventionally call them Z and W, and again these are not homologous among groups. Nor are sex chromosomes homologous between XY and ZW groups. Over evolutionary time, sex determination genes and systems come and go, sometimes quickly. See, for example, Ogata, M., H. Ohtani, T. Igarashi, Y. Hasegawa, Y. Ichikawa, and I. Miura. 2003. Change of the heterogametic sex from male to female in the frog. Genetics 164:613-620.

Bobsie · 6 January 2014

Thanks, IANAB but that makes some sense. I always thought the X and Y chromosomes we're so named due to their apparent physical two allele shape. Couldn't vision a W or Z chromosome but understand now those must just be labels for different sex chromosomes.

M. Wilson Sayres · 7 January 2014

Bobsie said: Thanks, IANAB but that makes some sense. I always thought the X and Y chromosomes we're so named due to their apparent physical two allele shape. Couldn't vision a W or Z chromosome but understand now those must just be labels for different sex chromosomes.

That is an easy mistake to make because all chromosomes (X, Y and non-sex chromosomes) look like X's part of the time. We have two copies (one from mom, one from dad) of each non-sex chromosome. Each of those will make a copy of itself. That leads to two X-shaped bodies of two sister chromatids, connected at the centromere, that are then pulled apart into the daughter cells: Here is a cartoon of mitosis. And here is a picture of the human chromosomes all with sister chromatids: karyotype.

John Harshman · 7 January 2014

Bobsie said: Thanks, IANAB but that makes some sense. I always thought the X and Y chromosomes we're so named due to their apparent physical two allele shape. Couldn't vision a W or Z chromosome but understand now those must just be labels for different sex chromosomes.

The X and Y chromosomes *were* originally named, in mammals, based on shape. But the term was then generalized to cover all species in which males were heterogametic, regardless of chromosome shape. Though in fact Y chromosomes tend to be smaller in all species than X because they suffer lots of deletion.

John Harshman · 7 January 2014

How many sex-determination systems are there? They fall into two classes: genetic and environmental. The latter includes temperature-dependent and age or hormone-dependent sex determination. The former includes XY, ZW, X0, haplodiploid, and allelic sex determination. What else is there? (I would consider monotremes just a weird version of XY.)

M. Wilson Sayres · 7 January 2014

John Harshman said: The X and Y chromosomes *were* originally named, in mammals, based on shape.

Cool, I didn't know that. Do you have a reference?

M. Wilson Sayres · 7 January 2014

John Harshman said: How many sex-determination systems are there? They fall into two classes: genetic and environmental. The latter includes temperature-dependent and age or hormone-dependent sex determination. The former includes XY, ZW, X0, haplodiploid, and allelic sex determination. What else is there? (I would consider monotremes just a weird version of XY.)

U/W systems are pretty cool. Haploids are either female, with the U, or male, with the V. They sometimes sexually reproduce, but live most of their lives as haploid males/females.

M. Wilson Sayres · 7 January 2014

U/V (not U/W)

John Harshman · 7 January 2014

M. Wilson Sayres said: U/V (not U/W)

I was thinking only of animals. Plants have lots of weird stuff, and protists even weirder.

John Harshman · 7 January 2014

M. Wilson Sayres said:
John Harshman said: The X and Y chromosomes *were* originally named, in mammals, based on shape.
Cool, I didn't know that. Do you have a reference?

Whoops. According to Wikipedia, this is an urban legend. But it's such a good one. Because it's nearly acrocentric, the Y looks more like a Y than most chromosomes. By the way, Wikipedia also says there are ZO systems, though it annoyingly gives no examples.

Wallace Barbosa de Souza · 11 January 2014

When are people here going to talk about the huge and surprising differences between human and chimp Y chromosome and how that flies on the face of evolution 'theory'? Reference: Nature 463, 536-539 (28 January 2010) doi:10.1038/nature08700

Wallace Barbosa de Souza · 11 January 2014

DS said: X-degenerate region (relics of the ancestral sex chromosomes) X-transposed region (transposed from the X to the Y after chimpanzee-human divergence) Ampliconic region (repetitive region, mostly acquired from the autosomes) It would be interesting to see how anyone who denies the common ancestry of humans and chimps would explain this organization of the Y chromosome. Most likely they will ignore it or make up some story about why the "designer" wanted to do it this way. Y remains a mystery to them.

No, it doesn't... Mystery for you is this: http://www.nature.com/nature/journal/v463/n7280/full/nature08700.html "By comparing the MSYs of the two species we show that they differ radically in sequence structure and gene content, indicating "rapid evolution" during the past 6 million years" Lol rapid evolution is an explaining away for huge differences between 'related' species that put evolution in great trouble..

DS · 11 January 2014

Wallace Barbosa de Souza said:
DS said: X-degenerate region (relics of the ancestral sex chromosomes) X-transposed region (transposed from the X to the Y after chimpanzee-human divergence) Ampliconic region (repetitive region, mostly acquired from the autosomes) It would be interesting to see how anyone who denies the common ancestry of humans and chimps would explain this organization of the Y chromosome. Most likely they will ignore it or make up some story about why the "designer" wanted to do it this way. Y remains a mystery to them.
No, it doesn't... Mystery for you is this: http://www.nature.com/nature/journal/v463/n7280/full/nature08700.html "By comparing the MSYs of the two species we show that they differ radically in sequence structure and gene content, indicating "rapid evolution" during the past 6 million years" Lol rapid evolution is an explaining away for huge differences between 'related' species that put evolution in great trouble..

That's funny, the reference you cited didn't conclude that this was a problem for evolution at all. In fact, they concluded that changes like this are quite common in evolution. I also noticed that you provided no alternative explanation. How do you explain these observations? Is this the way that an "intelligent designer" would have done things? Why?