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(https://directorsblog.nih.gov/2024/10/17/bacteria-flip-gene-segments-to-alter-proteins-surprisingly-often-with-implications-for-human-health/) Bacteria Flip Gene Segments to Alter Proteins Surprisingly Often, with Implications for Human Health
Oct 17th 2024, 10:00

Some bacteria can produce more than one protein from a gene by “flipping” stretches of DNA. Credit: Donny Bliss/NIH

Proteins are vital to our bodies. They serve as structural building blocks for our tissues and organs and are responsible for their functioning in both health and disease. Genes, like recipes, contain instructions for making proteins. Usually, each essential protein is produced from a single gene. Now, new research shows that some bacteria can actually produce two or more proteins from a single gene by “flipping” underlying stretches of DNA.

While scientists have long known that DNA inversions can occur in bacteria, this study is the first to describe these inversions, or “invertons,” within individual genes. What’s more, the findings, from research supported by NIH and reported in the journal (https://www.nature.com/articles/s41586-024-07970-4) Nature, suggest that this flipping happens more often than scientists suspected.

The findings, from (https://profiles.stanford.edu/ami-bhatt) Ami S. Bhatt at Stanford Medical School in Stanford, CA, and her colleagues, may have important implications, not only for bacteria, but also for human health. For example, bacteria’s ability to flip genes and alter proteins on their surfaces may restrict the ability of our immune systems to recognize and effectively respond to infectious microbes. Invertons also likely play roles in how our (https://www.genome.gov/genetics-glossary/Microbiome) microbiomes, the communities of microorganisms that live in and on us, develop and change within our bodies. Our microbiomes influence our metabolisms, immune responses, and more.

Scientists have long known that Salmonella bacteria, a frequent cause of food poisoning, can undergo phase variation and change proteins on its surface by flipping a certain stretch of DNA. In the new study, Bhatt’s team, including Patrick West and Rachael Chanin, wanted to learn more about how widespread this kind of flipping might be. They combined their expertise in data science, computational biology, microbiology, and bacterial genomics to develop a software tool they call PhaVa, which analyzes DNA sequences to find likely invertons.

PhaVa works by first scanning long-read DNA sequences to find areas that look like they might flip easily. Next, the software creates a catalog of what those sequences would look like if they flipped and compares those predicted sequences to true sequences in bacterial DNA datasets to uncover likely invertons. The software identified thousands of DNA inversions in many microbial species, including 372 invertons within genes in genomes of bacteria and another microbial group known as archaea. Altogether, the findings suggest that this kind of gene flipping is a common occurrence that may enable bacteria to respond to changing environments.

Interestingly, the researchers also looked for invertons in microbiome data collected from people undergoing stem cell transplants. The idea was that those microbes likely had encountered stressors, including chemotherapy and antibiotics, which might make gene flipping even more likely. Indeed, they found that invertons in these samples were especially numerous. The researchers also looked in detail at ten invertons in a bacterium often found in the human gut microbiome called Bacteroides thetaiotaomicron and found that inversions change a protein required to make thiamine (vitamin B1), affecting the way this bacterium grows in different environments. This serves as a good example of how these inversions might lead to important metabolic changes.

The researchers now want to investigate the mechanisms causing inversions. They expect that these findings are just the tip of the iceberg for understanding the role of invertons in bacteria’s ability to adapt and thrive. They also suggest that, as we learn more about links between this process in bacteria and human diseases, we might find ways to harness it for improving human health.

Reference:

Chanin RB, West PT, et al. (https://pubmed.ncbi.nlm.nih.gov/39322669/) Intragenic DNA inversions expand bacterial coding capacity. Nature. DOI: 10.1038/s41586-024-07970-4 (2024).

NIH Support: National Institute of Allergy and Infectious Diseases

Forwarded by:
Michael Reeder LCPC
Baltimore, MD

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