Bronchitis and pneumonia may be harmful, but by studying the genetic structure of the bacteria that causes them, EU-funded scientists have been able to gain a better understanding of how genes function. Their research suggests DNA is organised the same way in all living organisms, a finding that may hold the key to new vaccines and drug therapies.
Mycoplasma pneumoniae, one of the smallest known bacteria and the source of countless infections in humans and animals, has been found to have the same genetic structure as all living cells. The discovery, by EU-funded scientists based in Barcelona’s Centre for Genomic Regulation (CRG), shows that even in small organisms, genes are arranged in clusters that switch on or off together, with potential implications for new medicines and industrial processes.
By using super-resolution microscopy and a technique known as Hi-C, the scientists – supported by three EU-funded projects, CELLDOCTOR, 4D-GENOME and MYCOSYNVAC – were able to generate a 3D ‘map’ showing how Mycoplasma DNA is arranged or packaged. Their findings, published in the journal ‘Nature Communications’, prove that genes are grouped in different ‘domains’ even in the smallest of organisms, and that genes in the same domain tend to act together.
‘We had suspected that the Mycoplasma genome might have a similar overall organisation to other bacteria, but we were completely surprised to find that it was also organised into domains,’ said Marie Trussart, the lead author on the paper. ‘This research shows that the organisation and control of genes cannot be understood by just looking at the linear sequence of DNA in the genome.’
‘Big technical challenge’
Mycoplasma pneumoniae contains only 680 genes, makes just 20 or so DNA-binding proteins, and its chromosomes are five times smaller than larger bacteria like E. coli. And, unlike most bacteria, it lacks a cell wall, making it easily cultivated and genetically manipulated.
However, because of its size, the project was a ‘big technical challenge’, Trussart said, taking five years to complete. But thanks to expertise in Mycoplasma and structural genomics within the CRG, researchers led by Professor Luis Serrano were able to use the Hi-C technique – which reveals interactions between different pieces of DNA – to study more detailed patterns of organisation in the tiny bacterium.
What they found was that the Mycoplasma chromosome is organised into 44 chromosome interacting domains (CIDs), regions similar to those found in more complex cells. Genes inside the CIDs tended to be co-regulated, suggesting chromosome organisation influences gene transcription. And, scientists discovered, the way bacteria use supercoiling to pack in their chromosomes may play a role in the regulation of the domains.
These findings, together with the results of previous studies of larger bacteria, show that chromosome organisation in cells is not random – it is a common phenomenon of all life. Chromosomes are organised in a functional and dynamic manner – the only difference is they are packed into the nucleus in the case of eukaryotes, and into the cell in the case of bacteria.
The unexpected results suggest that researchers need to look beyond the long strings of genetic information contained in DNA. ‘Indeed, to get the full picture of gene regulation we need to look at the three-dimensional organisation of the chromatin that also coordinates gene activity,’ said Trussart.
The research leading to these results was jointly funded by the European Union Seventh Framework Programme, through the European Research Council, and the European Union‘s Horizon 2020 research and innovation programme.