Neurons, Genes, and Gene Expression
- Published29 Nov 2022
- Author Diane A. Kelly
- Source BrainFacts/SfN
Neurons inside the brain can differ in appearance and function. They can produce different types of neurotransmitters, determining whether their signals have excitatory or inhibitory effects in their circuits. They can have different assortments of neurotransmitter receptors, determining the cells’ sensitivity to the effects of specific neurotransmitters. And, in their cell membranes, neurons possess different combinations of receptors capable of detecting neuromodulators that influence neuronal behavior — for example, hormones such as vasopressin, estradiol, or cortisol.
All cells in your body, including neurons, contain the same DNA housing the same genes. Differences among your neurons result from differences in which genes direct cellular activities, a process called gene expression. Each cell (or cell type) builds proteins from a slightly different subset of genes in its genetic code, the same way different children will build different structures from the same starting set of Lego blocks.
The mechanisms that cause neurons to express some genes and not others are currently an area of intense research. Many of these mechanisms depend on chemical changes to chromatin, the complex of protein and DNA that compactly packages the long DNA molecule inside the nucleus. Genes that a cell is using to build proteins need to be accessible and are associated with open, unfolded chromatin, while unexpressed genes are typically in tightly packed regions. Chemical changes that tighten or spread out chromatin complexes can, respectively, shut down or activate the genes on that segment of DNA. These changes are reversible, giving neurons flexibility to alter the genes they express in response to hormonal cues and environmental changes.
The genes that affect neuron structure and function can also differ between individuals. Gene variants, or alleles, reflect differences in the nucleotide sequences that make up a gene. While different alleles code for forms of the same protein, the variants can produce structural differences that affect their function. An allele might code for a version of an enzyme that is less effective than the usual version, and specific alleles of some genes can even cause neurological diseases. For example, Tay-Sachs disease, a fatal degenerative neurological condition, is caused by mutations in a gene that codes for part of a fat-metabolizing enzyme called beta-hexosaminidase A. Because the variant enzyme is poor at breaking down specific fats, these build up in neurons and become toxic. There are many cases where small changes in genetic sequence affects how our brain can function, and in the next 10 years — with our capacity to sequence a person’s entire genome now possible — we will be able to move much closer to understanding the genetic basis of brain disorders.
Adapted from the 8th edition of Brain Facts by Diane A. Kelly.
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