Horizontal gene transfer helps bacteria to obtain foreign genes from the environment, which is not only an important driving force of bacterial evolution, but also the main way for transmitting virulence and drug resistance genes among different bacteria. However, the unregulated expression of newly acquired foreign genes will often adversely affect bacteria. For this reason, bacteria use xenogeneic silencers to identify foreign genes and inhibit their expression, a process called "xenogeneic silencing". Under appropriate conditions, the inhibition can be lifted, and the expression of foreign genes will enhance the survival competitiveness of the recipient bacteria. At present, researchers have found several families of xenogeneic silencers in different bacteria, including H-NS and MvaT in γ-proteobacteria, Bv3F in α, β, and γ-proteobacteria, Lsr2 in Actinobacteria, and Rok in Bacillus (Fig. 1). Xenogeneic silencers all use their C-terminal DNA binding domains to recognize foreign genes which are AT-rich, and self-oligomerize through their N-terminal domains, which can change the structure of DNA, inhibit transcription, and regulate the expression of foreign genes, especially those related to virulence and drug resistance.
Figure 1. Distributions of xenogeneic silencers H-NS, Bv3F, MvaT, Rok, and Lsr2 in different bacteria.
Over the past decade, Professor Xia Bin's research team has systematically studied the three-dimensional structures of known bacterial xenogeneic silencers Lsr2, H-NS, Bv3F, MvaT,and Rok, along with their molecular mechanisms for selective recognition of DNA,in collaboration with Professor Jun Liu and Professor William Wiley Navarre of the University of Toronto, and Professor Simon Dove of Harvard University. The related studies have been published on Proc Natl Acad Sci U S A (2010,107: 5154-9; 2011,108: 10690-5), Curr Opin Microbiol (2012,15: 175-81), PLoS Pathog (2015,11: e1004967), and Nucleic Acids Res (2018, 46: 10514-29; 2020, 48:9372-86). Recently, they published a review article "Xenogeneic Silencing and Bacterial Genome Evolution: Mechanisms for DNA Recognition Imply Multifaceted Roles of Xenogeneic Silencers" on Molecular Biology and Evolution, which comprehensively summarized the previous studies, compared the DNA binding preferences of different xenogeneic silencers, and described the corresponding structural features and molecular mechanisms in detail (Fig.2).
Figure 2. Structures and DNA recognition mechanisms of the DNA binding domains of Lsr2, H-NS, Bv3F, MvaT, and Rok.
Meanwhile, they further analyzed the distributions of xenogeneic silencers and the genomic characteristics of the host bacteria, and found that the DNA binding preferences of different xenogeneic silencers are closely related to the base composition characteristics of the corresponding bacterial genomes, so that xenogeneic silencers could effectively distinguish foreign genes from core genomic genes. The analysis also revealed that the genomic AT contents of bacterial species with the same xenogeneic silencer family proteins are distributed in a limited range, and are generally lower than those species without any known xenogeneic silencers in the same phylum/class/genus(Fig. 3), indicating that xenogeneic silencers play multifaceted roles on bacterial genome evolution. Their gene silencing functions not only enhance the ability of bacteria to obtain new genes through horizontal gene transfer, but also act as a selective pressure to eliminate adverse mutations, which promote bacterial evolution while help to maintain the stability of bacterial genomes.
Figure 3. Comparison of genomic AT contents of bacteria with or without xenogeneic silencers H-NS, Bv3F, MvaT, Lsr2, and Rok.
Professor Xia Bin's research group has long been devoted to the studies of the structures and interactions of biological macromolecules such as proteins and nucleic acids, as well as the molecular mechanisms by which they perform their biological functions. The first and co-corresponding author of this review paper is Dr. Duan Bo, a postdoctoral fellow in Prof. Xia’s research group. This work is supported by the National Natural Science Foundation of China, the National Key Research and Development Program of the Ministry of Science and Technology, and Beijing National Laboratory for Molecular Sciences.
Link to the article:
https://doi.org/10.1093/molbev/msab136
