Sex differences in genes

Genes are not just inherited instructions; cells also decide how strongly to use them, and a new Science study found small but widespread sex-linked differences in that activity across the adult human cortex. (science.org) The researchers analyzed more than 1 million individual cells from 169 postmortem samples taken from 30 adults — 15 females ages 26 to 71 and 15 males ages 27 to 78 — across six cortical regions. (science.org) Looking cell by cell let the team measure gene expression, the molecular readout of which genes are turned up or down, instead of averaging signals across whole chunks of brain tissue. The study reported that sex effects were patterned by cortical region, cell type, and gene rather than showing one uniform male-female split. (science.org) Most of the recurring signals came from autosomes, the 22 pairs of non-sex chromosomes, not just from X and Y chromosome genes. The authors said those autosomal signatures were linked to cortical architecture, hormone-responsive regulation, and genetic risk for disorders that differ by sex. (pubmed.ncbi.nlm.nih.gov) That matters because many brain conditions already show uneven rates by sex. Nature’s report on the paper said schizophrenia is diagnosed more often in males, while Alzheimer’s disease is more common in females, and the new dataset offers one route for studying those gaps at the level of specific brain cells. (nature.com) The paper does not argue that male and female brains fall into two sharply separate biological types. A 2024 Science Advances review noted that sex explains only a small share of variation in healthy adult brain structure, and the new work likewise described subtle expression differences rather than categorical divides. (science.org) The study also has limits built into its design. It focused on the cerebral cortex in adult postmortem tissue, so it does not by itself show how these patterns arise during development, how they change over time, or whether they directly cause disease. (science.org) Researchers have been building toward this kind of map for years. A 2020 Science paper from the Genotype-Tissue Expression, or GTEx, project cataloged sex differences in gene expression across 44 tissue sources and 16,245 RNA-sequencing samples from 838 adults, showing that sex-biased gene activity extends well beyond reproductive tissues. (science.org) What this new paper adds is resolution: not just whether a gene differs on average, but which exact cortical cell types show the difference and in which brain regions. The authors described the dataset as a resource for testing why risk genes for some neurological and psychiatric disorders may operate differently in females and males. (science.org)