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Noisy genes drive cells to distraction

A new article, Ordered patterning of the sensory system is susceptible to stochastic features of gene expression, published in the journal eLife on February 26, uncovers a fascinating discovery that sheds light on a fundamental question in biology. Molecules, including biomolecules, move and collide with one another randomly. Yet the biomolecules that make-up cells do so without necessarily making the cells behave randomly. How is this accomplished?

To answer this important question, investigators in the NSF-Simons Center for Quantitative Biology studied sensory cells in the Drosophila wing. Ritika Giri, a Ph.D. candidate in the Northwestern Interdisciplinary Biological Sciences Program was co-advised by Northwestern faculty Richard Carthew and Madhav Mani.

All animals are equipped with their body parts positioned and numbered in stereotyped ways. Some species are more stereotyped than others. In the animal kingdom, the fruit fly Drosophila is a superstar of stereotypic organization of its body pattern. Sensory neuron numbers and positions are highly reproducible between individual flies. Giri focused on the biomolecule Senseless, which programs cells to become sensory neurons. Senseless must be synthesized in cells for them to become neurons, but Giri found that Senseless molecule numbers fluctuate up and down randomly. Why then don’t cells randomly become neurons if Senseless numbers bounce up and down.

Giri found that cells control one another by communicating with each other, and this communication prevents fluctuating Senseless from spontaneously triggering neurogenesis. However, she found that if the Senseless gene was located in a certain neighborhood of the genome, the fluctuations became very large and overcame the built-in communication system. This caused random cells to become neurons and the flies had disordered body patterns.  

Giri’s work suggests that the genome can have “quiet” and “noisy” neighborhoods. If a gene like Senseless is located in a noisy neighborhood, then the random behavior of its biomolecular products causes random behavior in the cells that contain it. The work hints that the genome might be organized so that genes such as Senseless are evolutionarily selected to reside in quiet neighborhoods.

Richard Carthew is a professor of molecular biosciences, and the director of NSF-Simons Center for Quantitative Biology at Northwestern University.

Madhav Mani is an assistant professor of engineering sciences and applied mathematics, and an investigator with the NSF-Simons Center for Quantitative Biology at Northwestern University.

Citation information: Giri R, Papadopoulos DK, Posadas DM, et al. Ordered patterning of the sensory system is susceptible to stochastic features of gene expression. Elife. 2020;9:e53638. Published 2020 Feb 26. doi:10.7554/eLife.53638

Funding for this research was provided by the National Institutes of Health R35GM118144, Simons Foundation 597491, National Science Foundation 1764421, Pew Charitable Trusts Pew Latin American Fellows Program, Max Planck Society MPI Funding, Chancellor’s Fellowship of University of Edinburgh, the Northwestern University Data Science Initiative, and the Robert H Lurie Comprehensive Cancer Center.

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