The Science

Bacteria can evolve by exchanging genetic material through a process called recombination. This study used machine learning models combined with functional laboratory experiments to show that after recombination, a bacterial signaling system changed and expanded its protein family, despite considerable selective pressures in place that constrained new modifications.

Four panel graph showing how REC protein domains evolve under different selection pressure constraints. — Models of the evolution of the REC protein family in a sequence-fitness landscape. Courtesy M. Garber.

The Impact

Before this study, it was unclear how proteins could evolve when there is limited room for change and selection pressures are present. This research shows that neutral genetic changes can drive the innovation of new proteins. This discovery advances the current understanding of protein evolution and could help explain how microbes adapt and evolve in contaminated environments by sharing genes.

Summary

Many bacteria employ two-component systems, which are mechanisms made up of a sensor protein and a response protein, to detect and react to environmental changes. It is well understood that evolution of these two-component systems is highly constrained because any mutations that cause unfavorable interactions with other two-component systems encoded in the same genome will not be passed on to future generations. In the absence of such selection pressures, evolution proceeds neutrally. However, how evolution proceeds when selection pressures remain in place is less well understood. To understand how new two-component signaling systems emerge under constrained selection pressures, ENIGMA researchers employed machine learning to investigate the evolution of REC domains, which are common modules in bacterial signaling systems that function as two component sense-response switches, across the bacterial lineage. The researchers identified a within-gene-recombination event in the REC protein family and determined that following gene duplication and within-gene-recombination from this event, the protein evolved: variants of the protein became more genetically different from each other in response to environmental changes. Using the methods developed through collaborations at Berkeley Lab, they tested the predicted model of evolution by direct experimentation and confirmed that the REC protein system significantly changed and expanded its protein family following recombination.

Contact

Aindrila Mukhopadhyay, Staff Scientist, Biological Systems and Engineering Division
Lawrence Berkeley National Laboratory
amukhopadhyay@lbl.gov

Funding

This work was part of the Ecosystems and Networks Integrated with Genes and Molecular Assemblies (ENIGMA) (http://enigma.lbl.gov), a Science Focus Area Program at Lawrence Berkeley National Laboratory (LBNL), and is supported by the U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research, under contract number DE-AC02-05CH11231 between LBNL and the U.S. Department of Energy. A.A.N. was supported by a National Science Foundation Graduate Research Fellowship, fellow ID 2018253421.

Publications

Garber, M. E., Frank, V., Kazakov, A. E., Incha, M. R., Nava, A. A., Zhang, H., Valencia, L. E., Keasling, J. D., Rajeev, L. & Mukhopadhyay, A. REC protein family expansion by the emergence of a new signaling pathway. mBio 14, e02622-23 (2023). [DOI]:10.1128/mbio.02622-23 {PMID}:37991384 OSTI:2221817