Humanitarian Media Hub provides a brief from an article by Jenny Graves, Honorary Professor of Genetics and Research Associate to the Vice-Chancellor at La Trobe University, for the scientific media The Conversation.Differences between men and women in terms of intelligence and behaviour have been debated and disputed for decades. Now, more and more scientific evidence shows that hundreds of genes act differently in the brains of people of different sexes. Some of these genes may be linked to brain diseases that have a gender bias, such as Alzheimer’s or Parkinson’s disease. These differences are formed early in development and may therefore play a role in brain development. And they are not unique to humans, as similar findings have been observed in other primates.
Gene activity in the brains of men and women
Decades of research have confirmed differences between men and women in brain structure and function, as well as in susceptibility to mental disorders. Less clear was the extent to which these differences were due to genes and to environment. The influence of genetics can be assessed by directly measuring gene activity in the brains of men and women. Thanks to the complete sequencing of the human genome, it is now easy to determine how any of the approximately 20,000 genes are activated.
Genes are sections of DNA. In order for them to manifest themselves, their sequence is copied into messenger RNA (mRNA) molecules, which are then translated into proteins. These proteins perform the work necessary for the structure and functions of the body. Therefore, by sequencing all RNA (transcriptome) and comparing these sequences with known genes, scientists can measure the activity of each gene in a specific tissue — even within a single cell.
When the transcriptomes of brain tissues from hundreds of men and women were compared after death in 2017, significant differences in gene activity patterns were found. One-third of all 20,000 genes were more prominent in one sex than the other in certain tissues. The biggest differences were observed in the testicles and other reproductive organs, but interestingly, most other tissues also showed gender differences. For example, different RNA profiles were found in muscle samples from men and women, corresponding to differences in muscle physiology. A study of brain transcriptomes published earlier this year showed 610 genes more active in men and 316 in women.
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Which genes demonstrate sexual differences in the brain?
It is expected that genes located on sex chromosomes act differently in men (XY) and women (XX). Approximately 90% of genes with sex differences are located on regular chromosomes, two copies of which are present in both men and women. This means that their activity is influenced by a specific sex-specific signal. This is likely to be sex hormones — testosterone and oestrogen — as many “sex-biased” genes in the brain respond to them.
How are gender differences formed in the brain?
Differences in brain gene activity appear early in foetal development — long before puberty or even the formation of testicles and ovaries. Another study in 2025, which analysed 266 post-mortem foetal brain samples, showed that more than 1,800 genes were more active in males and more than 1,300 in females. These groups of genes overlapped with those observed in the adult brain. This suggests that some of the differences are caused by the direct influence of genes on sex chromosomes, rather than just hormonal changes.
Does this mean that men’s and women’s brains work differently?
It would be surprising if the difference in the activity of such a large number of genes had no effect on brain function. But at present, we do not know exactly which functions differ. Some patterns are already apparent. Many “female” genes are responsible for the functioning of neurons, while “male” genes are responsible for cell membranes and nuclear structures. Some genes are sex-specific only in certain areas of the brain, indicating their local role. At the same time, differences in RNA levels do not always lead to changes in proteins — cells can compensate for this imbalance, so not every difference has a functional consequence. Sometimes different developmental mechanisms lead to the same result.
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Brain health
It is particularly interesting that gender differences may be linked to susceptibility to certain brain diseases. Many genes associated with Alzheimer’s disease are more active in women, which may explain the double incidence of this disease among them. Studies in rodents have shown that the presence of the SRY gene, which is found only in males, may worsen the course of Parkinson’s disease.
The evolution of sex differences in brain gene function
Such patterns of gene expression are not unique to humans — they have also been found in rats, mice and monkeys. The sets of “male” and “female” genes in monkeys largely coincide with those in humans, indicating that these differences originated from a common ancestor that lived about 70 million years ago. Natural selection likely favoured genes that provided slightly different behavioural traits in males and females of our primate ancestors — and possibly even earlier, in the ancestor of all mammals or even all vertebrates. In fact, sex differences in gene expression during brain development have been found in all animals — even in the simplest ones, such as roundworms.
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