Study Finds Many Human Genes Function Like On-Off Switches

Gene expression, the process where cells use the genetic information encoded in DNA to produce proteins, has often been compared to a dimmer switch, with gene activity rising and falling as needed. However, University at Buffalo researchers have discovered that many human genes behave more like on-off switches, being either fully active or completely inactive.

By analyzing genetic data from over 900 individuals across 27 tissue types, the team identified nearly 500 “switch-like” genes. Unlike the gradual variation seen in most genes, these genes show expression levels that are either very high or very low. This research, published in Nature Communications, represents the first systematic study of such genes in multiple tissues.

The study points to hormones, genetic variation, and epigenetic markers as likely factors influencing this switch-like behavior. According to Omer Gokcumen, a co-corresponding author, “Understanding why we differ from each other, the sources of human diversity, is one of the fundamental questions in human genetics and anthropology. Our study provides new answers.”

Some switch-like genes are linked to various diseases and conditions, including infertility, impaired immune response to COVID-19, and vaginal atrophy in postmenopausal women. Gokcumen notes, “We believe switch-like genes could one day be used to diagnose and perhaps even treat diseases.”

The identification of these genes was made possible by recent advances in population-level RNA sequencing. The project began as an undergraduate research effort led by Naoki Masuda, aiming to analyze gene networks across organs. Unexpectedly, the team found that 473 genes displayed bimodal distributions—either on or off—unlike the typical unimodal, dimmer-like genes.

Most switch-like genes were tissue-specific, while a few were universally switch-like. The researchers suggest hormones drive tissue-specific switching, while DNA influences universal switching. As first author Alber Aqil states, “Hormones and DNA are two powerful factors that can push a gene into being switch-like. Typically, lots of small factors nudge a gene, causing its activity to vary, like a dimmer, but it appears that switch-like genes are controlled by one or just a few factors that have big effects.”