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Bacterial Genome Diversification Closely Tied To Chromosomal Hotspots

The gene repertoires of bacterial species are often very diverse, which is central to bacterial adaption to changing environments, new ecological niches, and co-evolving eukaryotic hosts. Novel genes arise in bacterial genomes mostly by horizontal gene transfer (HGT), a pervasive evolutionary process that spreads genes between, eventually very distant, bacterial lineages.

It is believed that the majority of genes acquired by HGT are neutral or deleterious and thus rapidly lost. Yet, HGT is also responsible for the acquisition of many adaptive traits, including antibiotic resistance in nosocomials.

Hence, genome diversification is shaped by the balancing processes of gene acquisition and loss, moderated by positive selection on some genes, and purifying selection on many others.

When bacteria accept new genetic material into their genomes, the gene shuffling usually occurs in a specific location, which Dr. Oliveira and his other colleagues from the Pasteur Institute in Paris identify as recombination hotspots.

The team at 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. And the results point

to roughly 1 percent of chromosome sites that accommodate transferred genes in bacterial genomes.

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.

In the course of their study using the procedure, they were able to identified more than 170,000 such genes, dubbed HTgenes. 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.

In a nutshell, we found that almost all bacteria make use of dedicated ‘reservoirs’ dispersed throughout the genome…to accommodate the flow of incoming genetic information,” notes Oliveira. The hotspots are representative of many of the adaptive traits of the genome; hotspots are areas that “undergo frequent renovation by genetic turnover,” according to Oliveira.

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.

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