HAVE YOU EVER ASKED YOURSELF WHY MENS ARE USUALLY TALLER THAN WOMEN
Human height is regarded as a prominent physical characteristic, and noticeable variation between the sexes is displayed through it, with greater average height being typically observed in adult males than in females. Although this difference is widely recognised, a complete understanding of the precise biological mechanisms driving this sexual dimorphism has not yet been achieved. However, light is being shed by recent research by pnas on the significant role played by gene dosage effects from the X and Y chromosomes.
One leading hypothesis is pointed to by scientists, involving differential expression of genes located in the pseudoautosomal region 1 (PAR1) on the X and Y chromosomes . Particular interest is being given to the SHOX gene, which is considered a key height-related gene within the PAR1. While it is generally thought that two functional copies of PAR1 genes are present in both sexes, owing to the region escaping typical X inactivation in females, evidence has been suggested that SHOX expression is reduced on the inactive X chromosome (Xi) compared to the active X in females. It is hypothesised that this differential expression results in higher SHOX expression in males (46,XY) than in females (46,XX), and thus, the observed height difference is contributed to by this mechanism.
The impact of sex chromosome gene dosage has been explored by using sex chromosome aneuploidies (SCAs) as models, which are kinda like natural experiments. These SCAs get characterised by having an unusual number of X or Y chromosomes—think Turner syndrome (45,X), Klinefelter (47,XXY), 47,XYY, or 47,XXX. By looking at folks with these conditions, the contributions of different genomic factors to height were figured out, like how the Xi chromosome’s dosage plays in or the Y chromosome’s role without male hormones.
A big study, which was done on over 928,000 people (including 1,225 adults with SCAs), gave some solid insights. Heights were compared across different chromosome setups, and five sex-related factors got modelled: Xi dosage, Y dosage (separate from male hormones), male hormones themselves, and syndromic stuff specific to Turner and Klinefelter. Turns out, the Y chromosome’s influence on height was found to be stronger than the X’s, which kinda surprised researchers.
It was found that an extra Y chromosome seems to give a bigger boost to height than an extra X chromosome does, even when stuff like male hormones is taken into account. Like, for each extra Y chromosome, about 3.1 cm more height was added compared to each extra Xi chromosome. This difference (they called it the ΔXiY effect, I think) was estimated to explain about 22.6% of the height gap between 46,XY males and 46,XX females, even if you ignore hormones and all that. So, the idea that less SHOX gene expression on the Xi chromosome in females is part of why men are taller got more support.
Also, the study looked at what happens if there’s a bad variant in the SHOX gene. Apparently, when there’s a loss-of-function SHOX variant, it seems to make a bigger dent in height for males than for females. This fits with the idea that X-inactivation messes with the PAR1 region on the female X, so if the SHOX variant is on the Y or the active X in males, it kinda hits harder.
Beyond just height, it is thought that SCA research could be used to shed light on how sex differences show up in various medical conditions, like autoimmune and neuropsychiatric disorders and some other things too. The effects of sex hormones and genomic variation are still being figured out, but by separating these, new insights might be gained into how these conditions actually come about. In the future, it is hoped that studies looking at gene expression in people who have unusual chromosome complements especially in important tissues like musculoskeletal tissue could help us understand more about how the number of sex chromosomes affects the way people look or function.
Although the findings of the study were mostly similar for different ancestry groups, there was an exception noticed for people of African ancestry. In this group, the height difference between 47,XXY and 46,XY was found to be bigger than the difference between 47,XXX and 46,XX, which seems a bit odd. This possible difference probably needs to be looked at more closely in SCA cohorts that are more ancestrally diverse.
In conclusion, strong evidence has been provided by this research that differences in gene dosage from the X and Y chromosomes especially when it comes to SHOX expression are probably the main reason for the sexual dimorphism that’s seen in human height. It was shown that the Y chromosome seems to contribute more to height than the Xi chromosome does, even when hormones aren’t taken into account, which really highlights how important genetic factors are for differences between the sexes. It’s hoped that more research using SCAs and looking closely at gene expression will keep helping us understand the complicated relationships between sex chromosomes, gene dosage, and human health.
