The supposition that the X chromosome only constitutes 3.4% seems a little low to me. That's probably close to true for # X coding genes / # total coding genes, but by length it's closer to 4.8%, which predicts the variability data better.
I think it's actually in Falconer where he predicts loci affecting quantitative traits are more likely to exist in non-coding regions even though it wasn't known how many loci were coding versus not. This supports the use of BP length instead of coding genes as the preferred measurement.
I checked, the X chromosome constitutes 4.95% of basepairs, 3.70% of variations, and 4.13% of protein coding regions. This is not too far from my simulation and won't have much effect. (Values computed by X value divided by chromosomes 1-22+X+Y+MT.).
>In women's bodies, each X chromosome is randomly turned on or off, so in effect, women's bodies get a half dose of each allele.
X chromosome effects on the brain escape inactivation:
See: Globally Divergent but Locally Convergent X- and Y-Chromosome Influences on Cortical Development: "The presence of a negative relationship between X dose and brain size—regardless of gonadal sex—is consistent with direct regulation of human brain size by X-chromosome-specific (i.e., non-PAR) genes that escape X-inactivation (Carrel and Willard 2005) although could potentially also arise through mechanisms that are independent of X-chromosome gene content."
An interesting study on the marginal effect of sex chromosomes on the brain (ctrl-f for "inactivation"): A Cross-Species Neuroimaging Study of Sex Chromosome Dosage Effects on Human and Mouse Brain Anatomy: "Total brain size was substantially altered by SCT in humans (significantly decreased by XXY and increased by XYY), but not in mice. Robust and spatially convergent effects of XXY and XYY on regional brain volume were observed in humans, but not mice, when controlling for global volume differences."
"To achieve a balanced gene expression dosage between males (XY) and females (XX), mammals have evolved a compensatory mechanism to randomly inactivate one of the female X chromosomes. Despite this chromosome-wide silencing, a number of genes escape X inactivation: in women about 15% of X-linked genes are bi-allelically expressed and in mice, about 3%. Expression from the inactive X allele varies from a few percent of that from the active allele to near equal expression. While most genes have a stable inactivation pattern, a subset of genes exhibit tissue-specific differences in escape from X inactivation. Escape genes appear to be protected from the repressive chromatin modifications associated with X inactivation. Differences in the identity and distribution of escape genes between species and tissues suggest a role for these genes in the evolution of sex differences in specific phenotypes. The higher expression of escape genes in females than in males implies that they may have female-specific roles and may be responsible for some of the phenotypes observed in X aneuploidy."
Only 15% of X chromosome genes, so that's not so many. But might be important ones:
"To achieve dosage balance of X-linked genes between mammalian males and females, one female X chromosome becomes inactivated. However, approximately 15% of genes on this inactivated chromosome escape X chromosome inactivation (XCI). Here, using a chromosome-wide analysis of primate X-linked orthologs, we test a hypothesis that such genes evolve under a unique selective pressure. We find that escape genes are subject to stronger purifying selection than inactivated genes and that positive selection does not significantly affect the evolution of these genes. The strength of selection does not differ between escape genes with similar versus different expression levels in males versus females. Intriguingly, escape genes possessing Y homologs evolve under the strongest purifying selection. We also found evidence of stronger conservation in gene expression levels in escape than inactivated genes. We hypothesize that divergence in function and expression between X and Y gametologs is driving such strong purifying selection for escape genes."
Interesting that humans have 5x as much escape as mice. Are humans an outlier? Did some searching to get a more systematic comparison with animals but no luck.
From Jordan Peterson lectures I remember that the differences in character traits are small until puberty and only then explode. I would expect the effect to be mediated by hormones, in particular testosterone.
This raises the question how do the male cells know in which direction to vary.
Consider the following thought experiment: take some males, and create a opposite sex clones by replacing the Y chromosome with another copy of his X. Now compare the distribution on say trait T, between the originals and the clones. Assume T_0 is the mean of the distribution. Presumably the female clones would smaller variability than the originals.
Now take a particular male, i, and compare his value of the trait to his clone's, presumably his value T_i for T will be more extreme than her value T_i'. But in order for this to happen the genes need to "know" in which direction to skew the male trait so it moves away from T_0, i.e., his genes need to know the value of T_0 and not just T_i.
Now what happens if we apply directional selection on trait T to the population for a few generations and repeat the experiment?
The supposition that the X chromosome only constitutes 3.4% seems a little low to me. That's probably close to true for # X coding genes / # total coding genes, but by length it's closer to 4.8%, which predicts the variability data better.
https://inquisitivebird.substack.com/p/understanding-greater-male-variability/comment/9632440#comment-9632817?utm_source=activity_item
I think it's actually in Falconer where he predicts loci affecting quantitative traits are more likely to exist in non-coding regions even though it wasn't known how many loci were coding versus not. This supports the use of BP length instead of coding genes as the preferred measurement.
3.4% was mentioned by https://journals.sagepub.com/doi/abs/10.1111/j.1745-6924.2009.01168.x. I should have checked.
https://en.wikipedia.org/wiki/Human_genome#Molecular_organization_and_gene_content
I checked, the X chromosome constitutes 4.95% of basepairs, 3.70% of variations, and 4.13% of protein coding regions. This is not too far from my simulation and won't have much effect. (Values computed by X value divided by chromosomes 1-22+X+Y+MT.).
>In women's bodies, each X chromosome is randomly turned on or off, so in effect, women's bodies get a half dose of each allele.
X chromosome effects on the brain escape inactivation:
See: Globally Divergent but Locally Convergent X- and Y-Chromosome Influences on Cortical Development: "The presence of a negative relationship between X dose and brain size—regardless of gonadal sex—is consistent with direct regulation of human brain size by X-chromosome-specific (i.e., non-PAR) genes that escape X-inactivation (Carrel and Willard 2005) although could potentially also arise through mechanisms that are independent of X-chromosome gene content."
An interesting study on the marginal effect of sex chromosomes on the brain (ctrl-f for "inactivation"): A Cross-Species Neuroimaging Study of Sex Chromosome Dosage Effects on Human and Mouse Brain Anatomy: "Total brain size was substantially altered by SCT in humans (significantly decreased by XXY and increased by XYY), but not in mice. Robust and spatially convergent effects of XXY and XYY on regional brain volume were observed in humans, but not mice, when controlling for global volume differences."
2005 probably useless. Later replication
https://link.springer.com/article/10.1007/s00439-011-1011-z
"To achieve a balanced gene expression dosage between males (XY) and females (XX), mammals have evolved a compensatory mechanism to randomly inactivate one of the female X chromosomes. Despite this chromosome-wide silencing, a number of genes escape X inactivation: in women about 15% of X-linked genes are bi-allelically expressed and in mice, about 3%. Expression from the inactive X allele varies from a few percent of that from the active allele to near equal expression. While most genes have a stable inactivation pattern, a subset of genes exhibit tissue-specific differences in escape from X inactivation. Escape genes appear to be protected from the repressive chromatin modifications associated with X inactivation. Differences in the identity and distribution of escape genes between species and tissues suggest a role for these genes in the evolution of sex differences in specific phenotypes. The higher expression of escape genes in females than in males implies that they may have female-specific roles and may be responsible for some of the phenotypes observed in X aneuploidy."
Only 15% of X chromosome genes, so that's not so many. But might be important ones:
https://academic.oup.com/mbe/article/27/11/2446/1120317?login=false
"To achieve dosage balance of X-linked genes between mammalian males and females, one female X chromosome becomes inactivated. However, approximately 15% of genes on this inactivated chromosome escape X chromosome inactivation (XCI). Here, using a chromosome-wide analysis of primate X-linked orthologs, we test a hypothesis that such genes evolve under a unique selective pressure. We find that escape genes are subject to stronger purifying selection than inactivated genes and that positive selection does not significantly affect the evolution of these genes. The strength of selection does not differ between escape genes with similar versus different expression levels in males versus females. Intriguingly, escape genes possessing Y homologs evolve under the strongest purifying selection. We also found evidence of stronger conservation in gene expression levels in escape than inactivated genes. We hypothesize that divergence in function and expression between X and Y gametologs is driving such strong purifying selection for escape genes."
Something to look into later, I guess.
Interesting that humans have 5x as much escape as mice. Are humans an outlier? Did some searching to get a more systematic comparison with animals but no luck.
Is greater male variability also seen in birds? They have the opposite chromosome configuration with females being WZ and males ZZ.
This paper says yes, but isn't terribly convincing:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423667/
From Jordan Peterson lectures I remember that the differences in character traits are small until puberty and only then explode. I would expect the effect to be mediated by hormones, in particular testosterone.
This raises the question how do the male cells know in which direction to vary.
Consider the following thought experiment: take some males, and create a opposite sex clones by replacing the Y chromosome with another copy of his X. Now compare the distribution on say trait T, between the originals and the clones. Assume T_0 is the mean of the distribution. Presumably the female clones would smaller variability than the originals.
Now take a particular male, i, and compare his value of the trait to his clone's, presumably his value T_i for T will be more extreme than her value T_i'. But in order for this to happen the genes need to "know" in which direction to skew the male trait so it moves away from T_0, i.e., his genes need to know the value of T_0 and not just T_i.
Now what happens if we apply directional selection on trait T to the population for a few generations and repeat the experiment?