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Bacterial Genome Analysis Highlights Horizontal Gene Transfer, Recombination Hotspots

NEW YORK (GenomeWeb) – New research suggests bacterial genome diversification is closely tied to the chromosomal hotspots where bacteria tuck away new sequences acquired by horizontal gene transfer (HGT).

Researchers from the Pasteur Institute and the French National Center for Scientific Research (CNRS) scrutinized more than 900 genome sequences to get a look at the distribution of mobile genetic elements and gene families in 80 bacterial species. The results, appearing online today in Nature Communications, pointed to roughly 1 percent of chromosome sites that accommodate transferred genes in bacterial genomes.

The team detected a slew of antibiotic resistance genes and mobile genetic sequences at such sites, along with homologous recombination involving core genes at sites surrounding hotspots where mobile elements did not turn up.

"Over-representation of hotspots, with fewer genetic elements, in naturally transformable bacteria suggests that homologous recombination and horizontal gene transfer are tightly linked in genome evolution," Pedro Oliveira and Marie Touchon, the study's co-first authors, and their colleagues wrote.

For the analysis, the researchers focused on 932 available genomes, representing 80 bacterial species. By teasing out sequences stemming from the core genome in this set, while taking into account the pan genome, accessory gene sets, and phylogenetic relationships between the bugs, they got a glimpse at the distributions of gene families in general as well as sequences specifically acquired through horizontal transfer.

The authors explained that "HGT events are defined gene per gene … not as blocks, because there are no tools available for the latter and because the goal of our work was to study the clustering of genes acquired by HGT without using a priori models."

With this approach, they identified more than 170,000 such genes, dubbed HTgenes. Quantifying the clusters of the HTgenes and tracking their distribution provided a closer look at HGT hotspot usage in the bacterial genomes.

Almost 73 percent of the between-core sequence sites were devoid of accessory gene sequences in the bacterial collection, while more than half of the HTgenes clustered in fewer than 2 percent of those sites — results supported by the team's subsequent simulations. These hotspots also appeared to be somewhat clade-specific, the group found, depending on chromosome size and HTgene content in a given species.

At these hotspots, the researchers often found genes related to processes such as cell motility, cell repair, transcription, replication, antibiotic resistance, or other forms of cell defense. Genes with essential functions turned up far less often and did not appear as prone to horizontal transfer, they noted.

Genetic diversity appeared high around hotspots that lacked HTgenes, too. There, the team saw signs of homologous recombination, leading to phylogenetically inconsistent distributions of some of the genes in the core genome.

"Hotspots concentrate most changes in gene repertoires, between genome diversification and organization, and should be treasure troves of strain-specific adaptive genes," the authors wrote.

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