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Patterns of Gene Expression Differ in Male and Female Primate Brains

NEW YORK (GenomeWeb News) – Male and female primates have distinct patterns of gene expression in at least one region of their brains, new research suggests.
In a paper appearing online today in PLoS Genetics, a team of Swedish and American researchers compared the gene expression in the cortexes of males and females from three primate groups — humans, macaques, and marmosets. They found much greater sexual dimorphism in gene expression in humans and macaques, representing ape and old world monkey groups, than in marmosets, a new world monkey.
Though it’s unclear what the functional consequences of this sex-biased gene expression are, if any, the findings may lead to a better understanding of the molecular differences between the sexes.
Sexual dimorphism, differences between male and female members of the same species, has been documented for many hormonal, behavioral, and physical traits — from color patterns to size. But sex differences in the brain are less well documented.
For this study, senior author Elena Jazin, a behavioral geneticist at Sweden’s Uppsala University, and her colleagues hypothesized that they might find “molecular dimorphism” in primate brains, specifically in terms of gene expression, and that these differences may have evolutionarily conserved regulatory effects.
To begin investigating this hypothesis, they looked at whether they could detect greater gene expression differences between males and females of the same species than from one individual to the next, focusing on the cortex, a brain region that’s responsible for higher level behavioral functions such as memory, language, and attentiveness.
Using a microarray from Sweden’s Royal Institute of Technology, the researchers probed about 14,600 annotated human genes in occipital cortex tissues from four male and four female humans, macaques, and marmosets.
While they found hundreds of genes with sex-biased expression in the humans and macaques tested, they detected a fraction of this sexual dimorphism in marmosets: fewer than ten genes tested showed sex-biased expression in the marmoset cortex.
When the team looked for conserved genes with sex-biased expression that overlapped in two or more of the species tested they found 85 genes with the similar patterns of sex-biased expression in humans and macaques. Just two genes, an X-factor inactivation-specific transcript and a heat shock factor binding protein gene, had the same sexually dimorphic expression pattern in all three primate species tested.
The sexually dimorphic gene expression in the cortex, particularly of humans and macaques, made the team suspect that they’d find similar expression differences in other tissues too. They searched available databases for tissue-specific gene expression patterns in the publicly available SOURCE database and found evidence to suggest that sex-biased genes might be under greater selective pressure in the nervous system than they are in reproductive tissues.
Of the 85 genes with human and macaque sex-biased expression, about 65 percent also had relatively high expression in nervous system tissue. Just slightly more than a quarter of the genes were highly expressed in reproductive tissues. In general, the researchers reported that female-biased genes also seemed to be under greater evolutionary constraints than genes with either male-biased or unbiased expression.
The team also investigated whether these genes were prone to regulation by male and female hormones. Based on the genes’ transcription initiation sites, the researchers reported that more than half of the orthologous genes with sex-biased expression in human and macaque brain contained estrogen response elements. Just over a quarter apparently contained androgen response elements.
“This finding establishes the existence of biological sex differences in gene expression in the human cortex, and further, it unveils the existence of conserved sexual signatures in the primate cortex with possible importance during primate evolution,” Jazin and her co-workers wrote. “Our results suggest that variation in expression of genes in the brain may be an important component of behavioral variation within as well as between species.”
Even so, the researchers have a ways to go before they can discern the functional consequences, if any, of these gene expression differences, lead author Björn Reinius, a researcher in Jazin’s lab, noted in a statement. And, because mismatches in cross-species microarray hybridizations — for instance, in the marmoset or macaque — could hinder their ability to detect differences in gene expression, the researchers conceded that sexually dimorphic gene expression in the primate cortex may be more extensive than this study suggests.
Still, Jazin and her team are confident that this research will lead to a better understanding of the sexual dimorphisms related to everything from physiology and behavior to treatment responses related to brain damage and disease.
Gene expression data from this study is available through the European Molecular Biology Laboratory-European Bioinformatics Institute ArrayExpress database.

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