Howarth, D. | bioRxiv Science

bioRxiv2025

On/off switches in the DIVARICATA-based regulatory network evolved through gene duplication, fusion, and truncation.

DIVARICATA (DIV) genes are MYB genes involved in many developmental processes in flowering plants. DIV-based regulatory networks involve paralogs of DIV (LFG and RADIALIS) that compete with DIV for either DNA or protein targets (like, the cofactor DRIF which is a distant paralog of DIV). These interactions act as on/off switches defining contrasting phenotypes. DIV proteins have multiple MYB domains; RADIALIS, LFG, and DRIF each have one. We determined the origin of these genes through Bayesian phylogenetic reconstruction. We report that DIV genes are a fusion of two simpler MYB genes. The first gene had two MYB domains (MYBA-MYB1), and the other gene had one MYB domain and a non-MYB HDI domain (MYB2-HDI). The ancestral DIV genes, hence, had four domains in the following sequence: MYBA-MYB1-MYB2-HDI. The MYBA domain was later lost, likely through a non-gradual truncation event leading to the following configuration in later-diverging DIV: MYB1-MYB2- HDI. The MYBA and MYB2 domains were derived from the SHAQKY clade. The MYB1 of DIV and the MYBD domains of DRIF were derived from the clade associated with the SANT2 domain of ZUO1/ZRF genes. LFG genes evolved from DIV by truncation of the MYB1 domain and the gain of repressor domains. We discuss how truncation of multi-domain DIV into RADIALIS and LFG was recruited towards on/off switches. Components of the DIV-based regulatory network, or their homologs, are present in a diversity of eukaryotes suggesting that their interaction may be ancestral to a large group of eukaryotes.

evolutionary biology↗

bioRxiv2020

Identification of colonisation and virulence determinants of Streptococcus pneumoniae via experimental evolution in mouse infection models

Streptococcus pneumoniae is a commensal of the human nasopharynx and a major cause of respiratory and invasive disease. Pneumococcus stimulates upper respiratory tract inflammation that promotes shedding from mucosal surfaces and transmission to new hosts. Colonisation and transmission are partially antagonistic processes. Adhesion to surfaces and evasion of host responses favours the former, whilst detachment, promoted by inflammation, is necessary for the latter. We sought to determine how adaptation and evolution of pneumococcus within its nasopharyngeal niche might progress when selective pressures associated with transmission were removed. This was achieved by serial passage of pneumococci in mouse models of nasopharyngeal carriage, manually transferring bacteria between mice. To assess the role of host environmental factors on pneumococcal evolution, we also performed analogous experimental evolution in a mouse pneumonia model, passaging pneumococci through lungs. Nasopharynx-passaged pneumococci became more effective colonisers, whilst those evolved within lungs showed reduced virulence. We observed selection of mutations in genes associated with cell wall biogenesis and metabolism in both nasopharynx and lung lineages, but identified prominent examples of parallel evolution that were niche specific. We focussed on gpsA, a gene in which the same single nucleotide polymorphism arose in two independently evolved nasopharynx-passaged lineages. We identified a single nucleotide change conferring resistance to oxidative stress and enhanced nasopharyngeal colonisation potential. We show that gpsA is also a frequent target of mutation during human colonisation. These findings highlight the role played by the host environment in determining trajectories of bacterial evolution and the potential of experimental evolution in animal infection models for identification of novel pathogen virulence and colonisation factors.

microbiology↗