Microbial Genetics

Microbial genetics examines the organisation, transmission and expression of genetic information in microorganisms, encompassing bacteria, archaea, fungi and viruses. Central themes include the structure and replication of chromosomal and extrachromosomal elements; mechanisms of mutation and DNA repair that shape genetic diversity; mobile genetic elements—transposons, plasmids and integrative conjugative elements—that drive horizontal gene transfer; and regulatory circuits that coordinate gene expression in response to environmental cues. Studies of mismatch repair, recombination pathways and genomic rearrangements illuminate how replication fidelity is balanced against adaptability. Conjugation, transformation and transduction mediate the flow of genes conferring traits such as antibiotic resistance or metabolic versatility. Advances in synthetic genetics—refactoring biosynthetic gene clusters, engineering yeast mating-type switches and mapping RNA–RNA interactomes—demonstrate how precise manipulation of microbial genomes can uncover fundamental principles and generate novel biotechnological tools. Insights from microbial genetics underpin our understanding of pathogen evolution, microbial ecology and the development of antimicrobial strategies, while also informing genome editing and synthetic biology approaches across the tree of life.

Research from Nature Portfolio

Engineered mating-type switching in Saccharomyces cerevisiae has been repurposed as a tunable genetic logic gate. By redesigning the recombination machinery and regulatory components, researchers achieved asymmetric cell differentiation within a clonal population. Haploid subpopulations, each bearing complementary mating-type identities, were programmed to express distinct enzymatic modules, enabling sequential bioconversion of xylan to xylose. This work exemplifies how reprogrammed genetic loci can establish controllable multicellular consortia for cooperative bioprocessing.

In methicillin-resistant Staphylococcus aureus, UV cross-linking and ligation of hybrids (CLASH) with RNase III as bait revealed hundreds of small RNA–RNA interactions under host-like conditions. Strikingly, sRNAs were found to converge on transcripts encoding membrane-permeabilising toxins, linking carbon metabolism to virulence factor expression. The study uncovered extensive post-transcriptional regulatory networks and an unexpected RNA sponging interaction between two abundant sRNAs, highlighting the complexity of sRNA-mediated control in pathogenic bacteria.

Research from all publishers

In budding yeast, the presence of nonhomologous 3′-flaps during single-strand annealing (SSA) dramatically increases the rejection of mismatches by the Msh2–Msh6 complex coupled with Sgs1 helicase activity. Engineering constructs with divergent repeats and variable flap lengths demonstrated that long 3′-tails stimulate heteroduplex rejection, whereas their removal shifts repair toward strand-biased correction. These findings clarify how DNA end structures govern the choice between error correction and recombination fidelity.

A genome-wide reporter assay in mouse embryonic stem cells showed that the length of the 3′ DNA overhang at a double-strand break imposes a strong bias on mismatch resolution during SSA. Systematic variation of flap lengths revealed that the strand bearing the longer 3′-flap was favoured by up to 80%, irrespective of break location or mismatch identity. Reversing flap asymmetry reversed the repair bias, underscoring the mechanistic role of end resection in directing mismatch correction.

In Caenorhabditis elegans, RNAi knockdown of the msh-2 gene over 50 mutation-accumulation generations led to a more than twentyfold increase in base substitutions and a 300-fold rise in small insertions/deletions. Whole-genome sequencing revealed an AT mutation bias and distinct rates on the X chromosome versus autosomes, suggesting chromosome-specific repair efficiencies. This metazoan study provides the first genome-wide mutation spectrum under impaired mismatch repair in an obligately outcrossing organism.

Microbial Genetics publication trend

The graph below shows the total number of articles in microbial genetics across all publications each year (not limited to Nature Index journals).

Technical terms

Mismatch repair (MMR): A conserved pathway that recognises and corrects base–base mismatches and small insertion–deletion loops arising during DNA replication or recombination.

Single-strand annealing (SSA): A double-strand break repair mechanism that anneals homologous repeats flanking a break, leading to deletion of the intervening sequence and generation of mismatches at annealed regions.

Heteroduplex rejection: The unwinding and rejection of mismatched DNA intermediates by MMR proteins and helicases to prevent recombination between divergent sequences.

3′-flap: A single-stranded DNA overhang at the 3′ end produced during end resection, which can affect strand discrimination in repair.

tRNA-mediated CLASH: An approach using RNase III cross-linking and ligation to capture in vivo RNA duplexes, enabling the discovery of sRNA–mRNA interactions.

Genetic logic gate: A synthetic genetic circuit engineered to produce defined outputs (gene expression) in response to specific inputs (e.g., recombination events).

References

1. Tunable cell differentiation via reprogrammed mating-type switching. Nature Communications (2024).
2. RNase III CLASH in MRSA uncovers sRNA regulatory networks coupling metabolism to toxin expression. Nature Communications (2022).
3. Nonhomologous tails direct heteroduplex rejection and mismatch correction during single-strand annealing in Saccharomyces cerevisiae. PLOS Genetics (2024).
4. Strand asymmetry influences mismatch resolution during single-strand annealing. Genome Biology (2022).
5. Mutation rate and spectrum in obligately outcrossing Caenorhabditis elegans mutation accumulation lines subjected to RNAi-induced knockdown of the mismatch repair gene msh-2. G3: Genes, Genomes, Genetics (2021).