Sexual dimorphism in cognition and behaviour: the role of X-linked genes

Abstract

Chimpanzees and humans last shared a common ancestor between 5 and 7 million years ago; 99% of the two species' DNA is identical. Yet, since the paths of primate evolution diverged, there have been remarkable developments in the behavioural and cognitive attainments of our species, which ultimately reflect subtle differences in gene structure and function. These modifications have occurred despite evolutionary constraints upon the diversity of genetic influences, on the development and function of neural tissue. Significant species differences can be observed both at the levels of function (gene expression) and structure (amino acid sequence). Protein evolution is driving an accelerating increase in brain complexity and size. Playing centre stage, in terms of the proportion of genes involved in brain development and cognitive function, is the X chromosome. Recently, it has become clear that a long-standing theory, implicating X-linked genes in a sexually antagonistic evolutionary role, is probably correct. Genes on the sex chromosomes can directly influence sexual dimorphism in cognition and behaviour, independent of the action of sex steroids. Mechanisms by which sexchromosomal effects, due to X-linked genes, influence neural development or function are reviewed. These include the biased expression of genes subject to X-inactivation, haploinsufficiency (in males) for non-inactivated genes with no Y homology, sex-specific brain functions and genomic imprinting of Xlinked loci. Evidence supporting each of these mechanisms is available from both human and animal models. Recently, the first candidate genes have been discovered.European Journal of Endocrinology 155 S99-S106

Building up the inactive X chromosome1

“…In addition, an increase in X-linked gene expression was observed in brain, with highest ratios in human, but not in mouse brain. This intriguing data further support earlier speculations on the role of the X chromosome in human cognition, mirrored by the higher frequency of mental retardation loci mapped on the X chromosome (for further reading, see Ropers, 2006;Skuse, 2006).…”

Sex-related variation in human behavior and the brain

“…The proposed link between prenatal testosterone and ASC has also been called into question by evidence that both males and females with gender identity disorder, rather than females only, are at increased risk of ASC 49. One possibility is that prenatal androgen exposure contributes to individual differences within the normal range in behaviors that show sex differences, but that developmental disorders that are more common in males, such as ASC, are more susceptible to direct genetic effects50, perhaps particularly those of genes encoded in the X and Y chromosomes 50-52.…”

A Role for the X Chromosome in Sex Differences in Variability in General Intelligence?

“…We have noted above that a large proportion of the genes encoding for proteins on the X chromosome are expressed in the brain. In addition, among genes expressed in the brain, a large proportion are X-linked and show very sex-biased expression patterns (Skuse, 2006). Together, the rapid evolution and concentration of X-linked genes in the brain suggest that specialization of these genes could be responsible for much of human cortical complexity and brain size.…”