Myxobacterial Genomics and Post-Genomics: A Review of Genome Biology, Genome Sequences and Related ‘Omics Studies

Myxobacteria are fascinating and complex microbes. They prey upon other members of the soil microbiome by secreting antimicrobial proteins and metabolites, and will undergo multicellular development if starved. The genome sequence of the model myxobacterium Myxococcus xanthus DK1622 was published in 2006 and 15 years later, 163 myxobacterial genome sequences have now been made public. This explosion in genomic data has enabled comparative genomics analyses to be performed across the taxon, providing important insights into myxobacterial gene conservation and evolution. The availability of myxobacterial genome sequences has allowed system-wide functional genomic investigations into entire classes of genes. It has also enabled post-genomic technologies to be applied to myxobacteria, including transcriptome analyses (microarrays and RNA-seq), proteome studies (gel-based and gel-free), investigations into protein–DNA interactions (ChIP-seq) and metabolism. Here, we review myxobacterial genome sequencing, and summarise the insights into myxobacterial biology that have emerged as a result. We also outline the application of functional genomics and post-genomic approaches in myxobacterial research, highlighting important findings to emerge from seminal studies. The review also provides a comprehensive guide to the genomic datasets available in mid-2021 for myxobacteria (including 24 genomes that we have sequenced and which are described here for the first time).

Functional human genes typically exhibit epigenetic conservation

Recent DepMap CRISPR-Cas9 single gene disruptions have identified genes more essential to proliferation in tissue culture. It would be valuable to translate these finding with measurements more practical for human tissues. Here we show that DepMap essential genes and other literature curated functional genes exhibit cell-specific preferential epigenetic conservation when DNA methylation measurements are compared between replicate cell lines and between intestinal crypts from the same individual. Culture experiments indicate that epigenetic drift accumulates through time with smaller differences in more functional genes. In NCI-60 cell lines, greater targeted gene conservation correlated with greater drug sensitivity. These studies indicate that two measurements separated in time allow normal or neoplastic cells to signal through conservation which human genes are more essential to their survival in vitro or in vivo.

Functional Human Genes Typically Exhibit Epigenetic Conservation

Recent DepMap CRISPR-Cas9 single gene disruptions have identified genes more essential to proliferation in tissue culture. It would be valuable to translate these finding with measurements more practical for human tissues. Here we show that DepMap essential genes and other literature curated functional genes exhibit cell-specific preferential epigenetic conservation when DNA methylation measurements are compared between replicate cell lines and between intestinal crypts from the same individual. Culture experiments indicate that epigenetic drift accumulates through time with smaller differences in more functional genes. In NCI-60 cell lines, greater targeted gene conservation correlated with greater drug sensitivity. These studies indicate that two measurements separated in time allow normal or neoplastic cells to signal through conservation which human genes are more essential to their survival in vitro or in vivo.

Bacterial protein interaction networks: connectivity is ruled by gene conservation, essentiality and function

Background: Protein-protein interaction (PPI) networks are the backbone of all processes in living cells. In this work we relate conservation, essentiality and functional repertoire of a gene to the connectivity k (i.e. the number of interactions, links) of the corresponding protein in the PPI network. Methods: On a set of 42 bacterial genomes of different sizes, and with reasonably separated evolutionary trajectories, we investigate three issues: i) whether the distribution of connectivities changes between PPI subnetworks of essential and nonessential genes; ii) how gene conservation, measured both by the evolutionary retention index (ERI) and by evolutionary pressures, is related to the connectivity of the corresponding protein; iii) how PPI connectivities are modulated by evolutionary and functional relationships, as represented by the Clusters of Orthologous Genes (COGs). Results: We show that conservation, essentiality and functional specialisation of genes constrains the connectivity of the corresponding proteins in bacterial PPI networks. In particular, we isolated a core of highly connected proteins (connectivities k≥40), which is ubiquitous among the species considered here, though mostly visible in the degree distributions of bacteria with small genomes (less than 1000 genes). Conclusion: The genes that support this highly connected core are conserved, essential and, in most cases, belong to the COG cluster J, related to ribosomal functions and to the processing of genetic information.

Genetic comparison of planted and natural Quercus robur stands in Russia

Genetic diversity and the optimal genetic composition are essential for the adaptability and adaptation of tree populations. Artificial regeneration of stands might reduce the genetic diversity and increase family structures if the seeds were collected from a limited number of mother trees. We did a genetic inventory in 12 pedunculate oak stands in Russia using a set of 366 nuclear gene markers (361 SNPs, 5 Indels) in order to look for differences in the genetic composition among natural and artificial stands. Our results did not reveal any systematic differences among both types of stands. However, we found two extreme cases of limited genetic diversity and increased proportion of full-sibs and half-sibs in urban man-made stands. The implications for the forestry and gene conservation programs were discussed.

FlaGs and webFlaGs: discovering novel biology through the analysis of gene neighbourhood conservation

Summary Analysis of conservation of gene neighbourhoods over different evolutionary levels is important for understanding operon and gene cluster evolution, and predicting functional associations. Our tool FlaGs (standing for Flanking Genes) takes a list of NCBI protein accessions as input, clusters neighbourhood-encoded proteins into homologous groups using sensitive sequence searching, and outputs a graphical visualization of the gene neighbourhood and its conservation, along with a phylogenetic tree annotated with flanking gene conservation. FlaGs has demonstrated utility for molecular evolutionary analysis, having uncovered a new toxin–antitoxin system in prokaryotes and bacteriophages. The web tool version of FlaGs (webFlaGs) can optionally include a BLASTP search against a reduced RefSeq database to generate an input accession list and analyse neighbourhood conservation within the same run. Availability and implementation FlaGs can be downloaded from https://github.com/GCA-VH-lab/FlaGs or run online at http://www.webflags.se/. Contact [email protected] Supplementary information Supplementary data are available at Bioinformatics online.