Aditi Kaveti ‘23

Natural genetic processes can lose their function over long-term evolution if that function requires too many resources to continue throughout generations. Scientists have been studying evolutionary reversibility, which is the ability to regain a lost function, in order to repair natural systems that have lost such valuable evolutionary processes. To this end in the field of synthetic biology, researchers employ and manipulate gene circuits–assemblies of biological parts encoding RNA or protein that enables individual cells to respond and interact with each other–in order to manually encode specific cellular regulatory mechanisms and gene activity.

Gábor Balázsi, Professor of Physical Physical and Quantitative Biology at Stony Brook University, has been studying the reversibility of evolutionary breakdown using yeast cell populations. Balázsi and his team employ a synthetic, positive-feedback gene circuit in which the man-made genetic material has been integrated with the yeast DNA. In the nature of the positive feedback mechanism, the more the products of the gene circuit are used up, the more that circuit functions, thus allowing the yeast to thrive have a better chance of passing on its genetic material to the next generation. In one study, the researchers integrated this circuit into haploid (possessing a single set of chromosomes) Saccharomyces cerevisiae cells to test if the population can restore this “lost” function. The goal of this experiment was to expose mutant populations to conditions where adaptation selection of gene circuit function would be beneficial. 

The researchers studied the activity of 7 positive-feedback mutant strains in the presence of drugs. Using drug resistance as a marker for positive feedback activation, scientists noticed 3 adaptation scenarios through genomic mutations that enhanced positive-feedback expression and affected transcription, translation, degradation, and other fundamental cellular processes. In these scenarios, the nonfunctional mutants were able to gain drug resistance, while the quasi-functional and dysfunctional mutants developed a high degree of basal, normal-level expression. The results of this study show how positive-feedback and synthetic biological mechanisms can be successfully employed gainfully to revitalize important networks of evolutionary dynamics.

Works Cited

[1] Kheir Gouda, M., Manhart, M., & Balázsi, G. (2019). Evolutionary regain of lost gene circuit function. Proceedings of the National Academy of Sciences of the United States of America, 116(50), 25162–25171. https://doi.org/10.1073/pnas.1912257116

[2] Image retrieved from: https://www.sciencephoto.com/media/493184/view/dna-gene-switch-circuit-board