REC protein family expansion by the emergence of a new signaling pathway

Megan E Garber; Vered Frank; Alexey E Kazakov; Matthew R Incha; Alberto A Nava; Hanqiao Zhang; Luis E Valencia; Jay D Keasling; Lara Rajeev; Aindrila Mukhopadhyay

doi:10.1128/mbio.02622-23

REC protein family expansion by the emergence of a new signaling pathway

mBio. 2023 Nov 22;14(6):e0262223. doi: 10.1128/mbio.02622-23. Online ahead of print.

Authors

Megan E Garber^{1

2}, Vered Frank², Alexey E Kazakov³, Matthew R Incha^{2

4}, Alberto A Nava^{2

5}, Hanqiao Zhang^{2

6}, Luis E Valencia^{2

6}, Jay D Keasling^{2

4

5

6

7

8}, Lara Rajeev², Aindrila Mukhopadhyay^{1

2

3}

Affiliations

¹ Department of Comparative Biochemistry, University of California, Berkeley, California, USA.
² Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
³ Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
⁴ Department of Plant and Microbial Biology, University of California, Berkeley, California, USA.
⁵ Department of Chemical and Biomolecular Engineering, University of California, Berkeley, California, USA.
⁶ Department of Bioengineering, University of California, Berkeley, California, USA.
⁷ Center for Biosustainability, Danish Technical University, Lyngby, Denmark.
⁸ Center for Synthetic Biochemistry, Shenzhen Institutes for Advanced Technologies, Shenzhen, China.

Abstract

We explore when and why large classes of proteins expand into new sequence space. We used an unsupervised machine learning approach to observe the sequence landscape of REC domains of bacterial response regulator proteins. We find that within-gene recombination can switch effector domains and, consequently, change the regulatory context of the duplicated protein.

Keywords: domain swapping; evolution; gene regulation; genetic recombination; large protein families; response regulator; signal transduction; two-component regulatory systems.