Adam's rib, revisited: Evolutionary divergence of mammalian sex chromosomes

Apr 18, 2012 by Stuart Mason Dambrot feature
X expression and autosomal expression in large protein complexes versus others. For each tissue, the ratio of the medians of X gene expression of large complexes and of X gene expression of other protein complexes was computed (the XL/XO ratio, in red). The ratio of the medians of autosomal gene expression of large complexes and of autosomal gene expression of other protein complexes—the AL/AO ratio (blue)—was computed similarly. The two green dashed lines indicate expectations with a twofold increase of expression (ratio of 2) and without any change in expression (ratio of 1). Image Copyright © PNAS, doi: 10.1073/pnas.1116763109

(Phys.org)—Males and females... Mars and Venus... XY and XX chromosomes—all are common memes. At the same time, the evolution of therian (placental and marsupial) sex chromosomes is less widely understood. More to the point, these arose some 150 million years ago from a pair of autosomes, or non-sex chromosomes. Having appeared, the X and Y chromosomes – both with the same ancestral genes – began diverging, with the Y chromosome evolving into a state in which (except for two small autosomal regions) it never recombines. As a result, the Y chromosome has degenerated, losing most of its genes in the process. On the other hand, the X chromosome does recombine, retains many ancestral genes – and has gained new genes, and evolved new expression patterns, as well.

The increased imbalance of X/Y chromosomal loci led to the emergence of loci-specific X chromosome inactivation, which has been seen as compensating for differential gene dosage (the number of copies of a given gene present in a cell or nucleus) by making expression of X-linked genes similar in males and females. Recently, using RNA sequencing, or RNA-seq, data (more precise than previously-analyzed microarray data), scientists in the Laboratoire de Biométrie et Biologie Évolutive, Université Lyon, Centre National de la Recherche Scientifique, in Villeurbanne, France, found support for the hypothesis that XCI acts as a dosage-compensation mechanism. At the same time, the scientists explored the contribution of dosage-sensitive genes to phenotype expression in X aneuploidy – a condition, relatively common in humans, in which one or more extra or missing chromosomes leads to an unbalanced chromosome complement, resulting in conditions such as Turner (X0) and Klinefelter (XXY) syndromes.

Associate Professor Gabriel A. B. Marais, PhD student Eugénie Pessia and other researchers faced a number of challenges in designing and implementing research to determine how and why female somatic inactivation evolved in mammals – especially given that it has been poorly understood. "When X-chromosome inactivation, or XCI, was first described in the 1960s, Susumu Ohno suggested that XCI evolved as part of a dosage compensation mechanism involving X chromosome hyperexpression in both sexes coupled with inactivation of one of the X chromosomes in females," Marais tells Phys.org. "However, the X hyperexpression part of Ohno's scenario has remained completely speculative for a very long time. Only recently, several studies have tried to compare the global X versus autosomal expression – the so-called X/A expression ratio – using microarray or RNA-seq data. Some found an X/A close to 1, others close to 0.5 – but the most recent studies from 2011 found a ratio of 0.7, which was difficult to interpret. We thought that maybe only some of X-linked genes need to be hypertranscribed and dosage-compensated, which would explain the X/A of 0.7 when all X-linked genes – that is, some with an X/A of 1 and some with an X/A of 0.5 – are analyzed together. We thought that it would make perfect sense if only the dosage-sensitive genes on the X chromosome would have an X/A of 1, as they're the ones that need a precise dosage."

The research team addressed these issues by studying gene expression of dosage-sensitive genes on the X chromosome – but since those are not very well known. "Based on studies in plants, yeasts and also in humans, we thought we should focus on protein-complex genes," Marais explains. "Protein complexes require a precise stochiometry to be functional, which means that if one protein is much more abundant than the other proteins of the complex, it is likely to be nonfunctional, which may be harmful for the cell." They used the data on human complexes from the HPRD database to get our list of protein-complex genes on the X chromosome.

"For large complexes," Marais continues, "we found that the expression levels estimated by RNA-seq are similar for X-linked and autosomal genes of a same complex. This is quite striking because both in male and female, only one X is present or expressed, whereas both autosomes are expressed. The X-linked genes have only one expressed copy and the autosomal two, so the expression of the X-linked genes should be half that of the autosomal ones, but we found it to be the same, which means the X-linked genes are hyperexpressed. How this hyperexpression is achieved remains an open question, but recent data in mice suggests that RNA polymerase II could be more abundant on these X-linked genes, probably because of epigenetic marks."

Looking ahead, Marais notes, "We'd like to study the other dosage-sensitive genes on the X chromosome, as we know that protein-complex genes are not the only ones. Genes involved in regulatory networks are probably dosage-sensitive. However, we need better characterization of these networks in humans before extending our analysis to these other dosage-sensitive genes."

Marais adds that the team would like to understand how XCI originated. "We showed that XCI is part of a dosage compensation mechanism for dosage-sensitive X-linked genes, because XCI downregulates their expression to get a balanced X and autosomal expression, and thereby avoid an X/A of 2, in females. However," he acknowledges, "our study does not provide insights on how XCI evolved in the first place. X-inactivation is found in placentals and marsupials – and in marsupials and in some tissues of some placentals, it is the paternal X that is always inactivated. David Haig has proposed that X-inactivation might originally be a form of genetic imprinting, which evolved because of parental conflicts. We'd like to test this idea."

Marais also points out that it might well be possible to transition to in silico modeling. "Actually, there's very little theoretical work on the of dosage compensation. The hypothesis proposed by David Haig has not been modeled at all," he notes, "and it would be important to show by simulation that his scenario can work."

Regarding research, technology and applications might benefit from their findings, Marais notes that in humans, most aneuploidies (aberrant number of chromosomes) are lethal. "Trisomy 21 is an exception, but there are strong effects on the phenotype known as Down syndrome. The X chromosome is another exception, and X aneuploidies have surprisingly mild effects given the size of this chromosome and the number of genes it contains compared to chromosome 21 – one of the smallest chromosomes in our genome. This is because all the supernumerary X are inactivated by XCI, so in XXY individuals or X0 individuals, only one X is expressed just like in XX or XY individuals. However, about 15% of the genes located on the human X chromosome escape XCI, and for these ones X aneuploidies will have consequences on gene dosage. Our results suggest that the consequences will be stronger for the dosage-sensitive genes." Marais concludes. He suggests that genes being both dosage-sensitive and XCI-escapees are probably the best candidates for underlying X aneuploidy syndromes such as Turner (X0), Klinefelter (XXY) and Triple-X. "The identification and characterization of such would of course help develop treatments that some patients affected by these very frequent syndromes need."

Explore further: Rock-paper-scissors model helps researchers demonstrate benefits of high mutation rates

More information: Mammalian X chromosome inactivation evolved as a dosage-compensation mechanism for dosage-sensitive genes on the X chromosome, Published online before print March 5 2012, PNAS April 3 2012 vol. 109 no. 14 5346-5351, doi: 10.1073/pnas.1116763109

4 /5 (14 votes)

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verkle
1 / 5 (22) Apr 18, 2012
Let's just study these chromosomes how they are today, and quick trying to posture what happened supposedly millions of years ago. Evolution will never be proven in the scientific sense. Focus your resources on the present.

P.S. It really is OK to believe in Adam. :)

BradynStanaway
4.2 / 5 (5) Apr 18, 2012
"P.S. It really is OK to believe in Adam. :)"

Maternal genes transfer.
Eve is more likely.

lrn2genetics.
Lurker2358
1 / 5 (6) Apr 18, 2012
"P.S. It really is OK to believe in Adam. :)"

Maternal genes transfer.
Eve is more likely.

lrn2genetics.


Not really.

You can make a female clone starting only with one male parent, assuming you have some sort of laboratory technology to grow the clone in an artificial maturation chamber.

You cannot make a male clone when starting only with a female parent.
jeandavid54
not rated yet Apr 18, 2012
In fact, in first place, sex chromosomes were simple A-type (A for autonomous, no replication). Then arrived B-type (B for Bored to be alone). Then C-type came in for Copy-that. Then type-D for Double-all, E-type erased after copy, and so on until X-type appeared (for crossing-needed) inviting Y-type to say "yes, mam !". Waiting now for Z-type to come (Z for zombies ?). Just kidding !
smd
5 / 5 (2) Apr 18, 2012
Waiting now for Z-type to come (Z for zombies ?). Just kidding !


Actually, Z chromosomes already exist - in birds.
Urgelt
5 / 5 (6) Apr 18, 2012
And so the commenters have taken us from Creationist nonsense to zombie birds.

If PhysOrg had a comment irrelevance meter, it would be pegged in the red about now.
CardacianNeverid
4.5 / 5 (8) Apr 19, 2012
Physorg editors should be shot! They present what is quite a technical article and then slap on a tard headline alluding to religious bullshit, just to stir things up. And it's worked, with the very first post by verkle tard. Waiting for kevin...
JVK
1 / 5 (1) Apr 19, 2012
In our 1996 Hormones and Behavior paper titled: From fertilization to adult sexual behaivor we mentioned that sex differences are apparent in the MAT locus of genes in yeasts that link them to sexual "orientation." It has become more clear that it is the epigenetic effect of nutrient chemicals on the MAT locus, and resultant changes in the mating factors of yeasts that clearly support the advent of sexual reproduction in unicellular organisms.
smd
not rated yet Apr 19, 2012
In our 1996 Hormones and Behavior paper titled: From fertilization to adult sexual behaivor (sic)...


Can you provide a link or DOI for your paper?
smd
not rated yet Apr 19, 2012
And so the commenters have taken us from Creationist nonsense to zombie birds.


The avian Z chromosome is real and has nothing to do with zombies :)
JVK
1 / 5 (1) Apr 19, 2012
1996 Hormones and Behavior paper titled: From fertilization to adult sexual behavior. Authors copy:
http://www.hawaii...ion.html

See also:
Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors
http://www.socioa...ew/17338
Citation: Socioaffective Neuroscience & Psychology 2012, 2: 17338 - DOI: 10.3402/snp.v2i0.17338

JVK
1 / 5 (1) Apr 19, 2012
Recently published in "Nature" by Jones, F et al is an article that extends my argument for nutrient chemical dependent calibration of individual survival and metabolism to pheromones that standardize and control reproduction from microbes to insects (invertebrates) to threespine stickleback fish (vertebrates). The conserved molecular mechanisms seem to be depend on pre-existing genetic variability, not random mutations.
smd
not rated yet Apr 19, 2012
1996 Hormones and Behavior paper titled: From fertilization to adult sexual behavior. Authors copy:
http://www.hawaii...ion.html
Citation: Socioaffective Neuroscience & Psychology 2012, 2: 17338 - DOI: 10.3402/snp.v2i0.17338


Thank you for both replies - much appreciated.
Deathclock
5 / 5 (3) Apr 20, 2012
Let's just study these chromosomes how they are today, and quick trying to posture what happened supposedly millions of years ago. Evolution will never be proven in the scientific sense. Focus your resources on the present.

P.S. It really is OK to believe in Adam. :)



Please don't ever pretend to be a scientist.

Science doesn't "prove" anything, for starters... that's pretty basic and you managed to f*ck it up anyway.

Epistemology, how does it work? Some people are so used to dogma they can't seem to shake it.
smd
5 / 5 (5) Apr 20, 2012
Science doesn't "prove" anything, for starters... that's pretty basic and you managed to f*ck it up anyway.


Thank you for making this important point. To expand on it, the scientific method is the process of trying to disprove an assertion through experimentation and observation. The longer a theory resists being disproved, the closer it comes to being regarded as "true" or "factual" (here's where epistemology and the sociology of knowledge come in).

A key example is Einstein's theories of relativity: for now, they've held up to all challenges. Note that conceptual or untested hypotheses don't count until they are duly tested: an accepted "theory" can have predictive value without any conformance to physical reality (e.g., ancient "turtles all the way down" cosmology).

Most importantly, herein lies the fundamental difference between science/knowledge and religion/belief: science seeks to disprove its assertions; religion seeks to uphold them at all costs.
HydraulicsNath
not rated yet Apr 23, 2012
is it possible that the beginning chromosomes were possibly A-sexual and throughout time various groups of chromosomes lost that ability and had become Reproductive through gene transfer?

Just a hypothesis but i would like to see an opinion or so.
Ethelred
3 / 5 (2) Apr 23, 2012
is it possible that the beginning chromosomes were possibly A-sexual
More like almost completely certain. Though chromosomes don't have sex on their own.

Simpler life doesn't have chromosomes. It has DNA rings and those rings can be captured from other organisms. Either by non-hostile exchange or eating each other.

Ethelred
JVK
3 / 5 (2) Apr 23, 2012
Simpler life doesn't have chromosomes. It has DNA rings and those rings can be captured from other organisms. Either by non-hostile exchange or eating each other.


I don't think ingestion of heterospecific DNA by microbes is widely known, and was reluctant to suggest it as a precursor to the self / non-self recognition that accompanies the adaptive evolution of sex differences in yeasts. But, I did in:
Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors
http://www.socioa...ew/17338 My academic and commercial interest in this complex ability in bacteria that suppress reproduction with pheromones when insufficient nutrients are available led me to sponsor the video game "Bacillus." One entitlement is that I get to name an organism and attribute to it a characteristic. If a named organism eats the DNA of other bacteria, I named it!
Citation: Socioaffective Neuroscience & Psychology 2012, 2: 17338 - DOI: 10.3402/snp.v2i0.17338

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