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Monday, December 23, 2019

What does the Y chromosome do?

Is it really possible for a person to change sex? Do other animals have Y chromosomes? Some facts about our most beloved chromosome

T here seems to be a lot of confusion among the general public about sex and biology these days. Here are some facts about the Y chromosome, that small but beloved piece of DNA that determines whether you are a male or a female.

1. What is a chromosome?

A chromosome is a long linear strand of DNA that is packed into a compact unit along with a large number of proteins (mainly histones) that control the expression of the proteins that the DNA codes for. Every somatic cell in your body has two copies of each of the 23 chromosomes, for a total of 46. Sex is determined by the X and Y chromosome: females have XX and males have XY.

2. What does the Y chromosome do?

The Y is transmitted unaltered from father to son. The presence of a Y chromosome means that males are very slightly more genetically complex than females. In practice, this doesn't mean much because much of our DNA is repressed and not really used. However, it does mean that females tend to cluster more around the mean in some traits, while males tend to be more variable. It also means if there's a genetic disorder like color blindness that is caused by a mutation on the X chromosome, males are more likely to suffer from it.

3. What genes are on the Y chromosome?

There are 568 genes on the Y chromosome. The most important one is Sry, a transcription factor that determines maleness during embryogenesis. Sry is also expressed in the brain, and changes the brain's function directly (that is, not through testosterone). This happens especially in dopamine-containing regions, and it's been speculated that this could account for sex differences in Parkinson's disease (which is higher in males) and mood disorders (which are higher in females)[1][2].

The Y chromosome was formed in evolution by duplication of the X, and lost most of the duplicated genes over time. The Y chromosome has only 36% as much DNA as the X. Only 71 of the 568 Y-chromosome genes can be translated into proteins; 27 of these are male-specific, which is to say they don't have a paralogue on the X chromosome. Most of them are related to male traits like spermatogenesis, but some, like PCDH11Y (which codes for protocadherin 11Y), are brain-specific[3].

At one time, some researchers thought that the Y chromosome was destined to disappear. It is now known that the Y influences important immune and inflammatory processes in men that provide advantages as well as risks. This is very important for health: twice as many women as men have Alzheimer's disease, and women comprise 60% of stroke-related deaths. It's thought that this is caused by differences in anti-inflammatory responses to brain injury[4]. Sex differences in the microglia, which are the immune cells of the brain, account for many of the differences in how male and female brains repair themselves[5].

Many gene products activate or inhibit the expression of proteins encoded on other chromosomes. An example is anti-Müllerian hormone, or Müllerian inhibiting substance, a protein on chromosome 19 that mediates male sexual differentiation.

Thanks to the Human Genome Project, we also know that half the expressible genes on the Y are expressed in non-gonadal tissue including the brain. We also know that the earlier theory that all sex differences in brain are due to testosterone is false[6].

4. Why are women called mosaics?

Since females get two doses of X, researchers think that female cells need to balance the dosage to prevent cells from expressing twice as many X chromosome proteins as they need. This is called Ohno's hypothesis. One way this happens, Ohno hypothesized, is by X-chromosome inactivation.

Inactivation is caused by Xist (X inactivation-specific transcript), which is a non-coding gene on the X chromosome[7]. Xist is a long noncoding RNA molecule that inactivates the extra X during embryogenesis, silencing its expression. In each cell with two or more X's, this long non-coding RNA turns all but one of the X's into a Barr body, where it remains for life, even after the cells divide.

This means that half the cells in each female contain an X chromosome from the mother and half contain an X chromosome from the father. This is called mosaicism. In cats, where the gene for fur coloration is found on the X chromosome, mosaicism results in tortoiseshell and calico coloration in the female. Male tortoiseshell cats are rare and usually sterile.

X-chromosome silencing is not perfect; about 15–25% of the inactivated chromosome's genes are actually transcribed, though at a lower level. These are called escape genes. Humans have more escape genes than other species, and thus they have more genetic diseases that occur in one sex but not the other. By contrast, 40% of the genes on the active X chromosome are expressed. It has been estimated that 10% of these genes cause mental retardation when they have a mutation.

As with Sry, it has been speculated that Xist might have female-specific effects on autosomes (non-sex chromosomes). In fact, hundreds of genes are expressed differently in brain between males and females. Studies on mice showed that many of these changes are independent of testosterone.[8] These differences contradict the earlier belief that male and females brains are identical. In fact, only about 95% of the genome is the same between the two sexes.[6]

5. What is aneuploidy and how does it affect your brain?

Aneuploidy is a condition when the number of chromosomes in the person's cells is incorrect. Down syndrome, where there are three copies of chromosome 21, is an example. There are four main types of sex chromosome aneuploidy:

Most common types of sex chromosome aneuploidy
 Name    Sex    Karyotype  
Klinefelter syndrome M XXY, XXXY, or XXXXY
Trisomy X F XXX
Turner syndrome F X0 (sometimes called XO)
XYY syndrome M XYY
If viewing on a cell phone, drag table left or right to scroll.

In women with XXX karyotype or men with Klinefelter syndrome, all but one of the X chromosomes are inactivated. Women with Turner syndrome have characteristic swollen neck (neck webbing), low-set ears, cardiovascular abnormalities, ADHD, and normal IQ, but poor math and spatial visualization ability, and are usually infertile.

Humans with aneuploidy have a high risk of neuropsychiatric disorders, further demonstrating the importance of sex chromosomes in the brain.

Neuropsychiatric disorders associated with sex chromosome aneuploidy
 Karyo­type    % with autism   % with ADHD   % psychotic dis­orders*    % with anxiety dis­order   % with de­pres­sion 
XY 7.312.9
XXY 25 35 12 20.526.9
XXX 15 30 13 19.517–54
XYY 30 69 8** 26 13
If viewing on a cell phone, drag table left or right to scroll.
*schizophrenia or bipolar disorder ** bipolar reported only

6. Do other species have Y chromosomes?

Yes. Most mammals and some insects have the XX/XY system.

7. Can you have a male brain in a female body, or vice versa?

Feminists sometimes claim that male and female brains are identical. If that is the case, then the answer is no. However, a large amount of scientific evidence confirms that male and female brains differ in significant ways, both in size and in how the neurons are interconnected, which is to say males and females think differently. Obviously a person can feel more masculine or more feminine than average, but the brain cannot be a different sex than the rest of the body, so the answer is still no.

The idea that there are hundreds of genders and that one can change from one to the other at will without any visible external change has little empirical support, so it is generally regarded in science as a social construction. The fact that a person's ‘gender’ so used has no practical consequence means that the term ‘gender’ has an ambiguous meaning and is actually confusing, which might explain why its use is falling out of favor in science (though not in sociology, where being confusing is considered an advantage).

8. How could a person change from a male into a female or vice versa?

When a person requests a sex change, they are given surgery and hormones that make the person appear more like the opposite sex. This is done in the belief that it will make the person happier. However, it does not really convert the person into a member of the opposite sex. Biologically the only way to do this would be to change the chromosome composition at the earliest stage of embryogenesis before development begins.

To be female, a person needs the potential ability to be fertilized and produce babies. Giving female hormones to a male does not create the biological machinery to do this, nor does it rewire the brain to experience the world as a female does. It also does not eliminate the Y chromosome, which makes every cell in the body irrevocably male. Likewise, giving male hormones to a female cannot change her into a male or create a Y chromosome where none exists.

Merry Christmas to all. I mean, it is anticipated that the reader is currently experiencing satisfactory Christmas-related phenomena.

1. Dewing P, Chiang CWK, Sinchak K, Sim H, Fernagut PO, Kelly S, Chesselet MF, Micevych PE, Albrecht KH, Harley VR, et al. (2006). Direct regulation of adult brain function by the male-specific factor SRY. Curr Biol 16:415–420.

2. Czech DP, Lee J, Correia J, Loke H, Moller EK, Harley VR. (2014). Transient neuroprotection by SRY upregulation in dopamine cells following injury in males. Endocrinology 155:2602–2612.

3. Maan AA, Eales J, Akbarov A, Rowland J, Xu X, Jobling MA, Charchar FJ, Tomaszewski M1. (2017). The Y chromosome: a blueprint for men's health? Eur J Hum Genet. 25(11), 1181–1188. PMID: 28853720 PMCID: PMC5643963 DOI: 10.1038/ejhg.2017.128

4. Kerr N, Dietrich DW, Bramlett HM, Raval AP. (2019). Sexually dimorphic microglia and ischemic stroke. CNS Neurosci Ther. 25(12), 1308–1317. PMID: 31747126 PMCID: PMC6887716 DOI: 10.1111/cns.13267 Link

5. Rahimian R, Cordeau P, Kriz J (2019). Brain response to injuries: when microglia go sexist. Neuroscience 205, 14–23.

6. Arnold AP. (2017). A general theory of sexual differentiation. J Neurosci Res. 2017 95(1–2):291–300. PMID: 27870435 PMCID: PMC5369239 DOI: 10.1002/jnr.23884

7. Noordam MJ, Repping S. (2006). The human Y chromosome: a masculine chromosome. Curr Opin Genet Dev. 16(3), 225–232. PMID: 16650761 DOI: 10.1016/j.gde.2006.04.018

8. Xu J, Disteche CM. (2006). Sex differences in brain expression of X- and Y-linked genes. Brain Res. 1126(1),50–55. PMID: 16962077 DOI: 10.1016/j.brainres.2006.08.049

9. Posynick BJ, Brown CJ. (2019). Escape From X-Chromosome Inactivation: An Evolutionary Perspective. Front Cell Dev Biol. 7, 241. PMID: 31696116 PMCID: PMC6817483 DOI: 10.3389/fcell.2019.00241 Link

dec 23 2019, 9:25 am. edited dec 24 2019, 4:34 am

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