Very little is known about differences in gene activity between males and females, or what the implications of differences might be
If body physiology differs between males and females, it follows that the activity of genes should be different too.
Males and females have the same genes, except for those few extra genes present on the male-specific Y chromosome. Some of these are needed to build male body parts, such as the testes, while the purpose of others is less clear.
But it is not just the presence or absence of genes that is important in biology: crucial factors also include when and where they are active.
In fact, this has not been extensively studied and very little is known about sex differences in gene activity. In one US study, for example, researchers tried to explain differences in male and female muscle architecture by looking at gene activities. Although there were identifiable differences in the activity, or ‘expression’, of certain genes, it was not obvious how or if these led to physical differences in muscle mass.
Not surprisingly, significant differences are seen in gene expression in ovaries and testes, which share the same origins in the early embryo. In a number of species – including flatfish, mice, chickens and humans – tens, hundreds or even thousands of genes are more active in one or other organ.
Interestingly, studies of fruit flies suggest that some genes involved in immune responses are less active in males than in females. This may have an impact on how males and females fight disease.
Liver gene pool
One organ where sex differences in gene activity have been linked to biological effects is the liver – more than 1,000 genes in this organ are expressed differently in men and women.
One of the liver’s most important roles is in ridding the body of toxins. Central to this activity are an important set of enzymes, the cytochrome P450s. These enzymes metabolise hormones, drugs and toxins.
It is possible that variation in human cytochrome P450 gene activity could explain sex differences in responses to pharmaceuticals. For example, drugs including the antibiotic erythromycin, the immunosuppressant cyclosporine and the blood pressure medicine nifedipine are metabolised by the CYP3a family of cytochrome P450s and are cleared faster by women than men.
The differing gene activity in the liver may be driven by sex differences in growth hormone release. In male and female rodents growth hormone release is cyclical, but the pulses are more common and smaller in females. The molecular mechanisms underlying potential differences in humans are still unexplained.
How important are these differences? In some cases doses of drugs do need to be tailored to someone’s sex. For example, women’s heart rhythms differ slightly from men’s. Drugs that affect heart rhythm as a side-effect (as a number do) can be particularly hazardous to women.
Whether this is an exception or highlights a general need to identify the effects of drugs separately in men and women is still debated. According to some studies, women may be up to twice as likely as men to have an adverse drug reaction. One 2011 study found that women account for around 57 per cent of all hospital admissions related to adverse drug reactions in the Netherlands.
Some say that, overall, the effects of sex are just part of a broad range of genetic responses that vary across different people. Others argue that the differences are big enough to matter. In the near future personalised medicine may offer the opportunity to tailor individual treatments based on genetics. Sex may play an important part.
What about that most critical organ, the brain? There is good evidence to suggest that the genes that are expressed in human brain cells differ between men and women. The differences cover all major areas of the brain and 2.5 per cent of the genes expressed in it – and may affect the susceptibility of men and women to brain disease.Lead image:
courtney/Flickr CC BY NC ND
- Sex-related differences in gene expression in human skeletal muscle (2008)
- Identification of differential genes in ovary relative to testis and their expression patterns in half-smooth tongue sole (2010)
- Gene expression during sex determination reveals a robust female genetic program at the onset of ovarian development (2005)
- Isolation and characterization of sexual dimorphism genes expressed in chicken embryonic gonads (2009)
- Global gene expression in the human fetal testis and ovary (2009)
- Genotype and gene expression associations with immune function in Drosophila (2010)
- X-linked variation in immune response in Drosophila melanogaster (2009)
- Information on cytochrome p450
- Sex differences in the expression of hepatic drug metabolizing enzymes (2009)
- Transcriptional profiling of human liver identifies sex-biased genes...polygenic dyslipidemia and coronary artery disease (2011)
- Women and abnormal heartbeats
- Sex-related differences in hospital admissions attributed to adverse drug reactions in the Netherlands (2011)
- Widespread sex differences in gene expression and splicing in the adult human brain (2013)
- Different gene expression in male and female brains helps explain differences in brain disorders