Researchers created a tailor-made gene sequencing method to accurately measure a biochemical, DNA tagging system, which switches genes on or off. This helped them study the system in any cell type, including human, plant and bacterial cells. While the results supported the idea that this system may occur naturally in non-bacterial cells, the levels were much lower than some previous studies reported and were easily skewed by bacterial contamination or current experimental methods. Experiments on human brain cancer cells produced similar results.

To address this, the scientists created a tailor-made gene sequencing method which relies on a new machine learning algorithm to accurately measure the source and levels of tagged DNA. This helped them distinguish bacterial DNA from that of human and other non-bacterial cells. While the results published in Science supported the idea that this system may occur naturally in non-bacterial cells, the levels were much lower than some previous studies reported and were easily skewed by bacterial contamination or current experimental methods. Experiments on human brain cancer cells produced similar results.

«Pushing the boundaries of medical research can be challenging. Sometimes the ideas are so novel that we have to rethink the experimental methods we use to test them out,» said Gang Fang, PhD, Associate Professor of Genetics and Genomic Sciences at Icahn Mount Sinai. «In this study, we developed a new method for effectively measuring this DNA mark in a wide variety of species and cell types. We hope this will help scientists uncover the many roles these processes may play in evolution and human disease.»

The study focused on DNA adenine methylation, a biochemical reaction which attaches a chemical, called a methyl group, to an adenine, one of the four building block molecules used to construct lengthy DNA strands and encode genes. This can «epigenetically» activate or silence genes without actually altering DNA sequences. For instance, it is known that adenine methylation plays a critical role in how some bacteria defend themselves against viruses.

For decades, scientists thought that adenine methylation strictly happened in bacteria whereas human and other non-bacterial cells relied on the methylation of a different building block — cytosine — to regulate genes. Then, starting around 2015, this view changed. Scientists spotted high levels of adenine methylation in plant, fly, mouse, and human cells, suggesting a wider role for the reaction throughout evolution.

However, the scientists who performed these initial experiments faced difficult trade-offs. Some used techniques that can precisely measure adenine methylation levels from any cell type but do not have the capacity to identify which cell each piece of DNA came from, while others relied on methods that can spot methylation in different cell types but may overestimate reaction levels.

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Materials provided by The Mount Sinai Hospital / Mount Sinai School of Medicine. Note: Content may be edited for style and length.