The Mystery of Hidden Genes: How Bacteria Encode Outside Their Genome and What It Means for Us

Since the genetic code was first decoded in the 1960s, genes have been seen as an open book. By analyzing our chromosomes as linear sequences, much like reading a novel, scientists can identify genes and understand how alterations in their code impact health.

This straightforward view of genetics was believed to apply universally, from humans to bacteria. However, recent research from Columbia University reveals that bacteria defy this model by creating free-floating, ephemeral genes, suggesting that similar genes might exist outside our own genome.

According to Samuel Sternberg, an associate professor of biochemistry and molecular biology at Vagelos College of Physicians and Surgeons, and Stephen Tang, an MD/Ph.D. student, this discovery challenges the idea that the chromosome contains the complete set of instructions for protein production. In bacteria, there are crucial instructions not encoded in the genome but still essential for survival.

Published in Science, this research has been described as "alien biology," "astonishing," and "shocking" by the scientific community. The unexpected findings led to a shift from skepticism to amazement as the mechanism was uncovered.

Bacteria and their viruses have been in a constant struggle, with viruses trying to insert their DNA into bacterial genomes and bacteria evolving defense mechanisms such as CRISPR. The defense system examined by Sternberg and Tang is unusual, involving an RNA with an unknown function and a reverse transcriptase enzyme that synthesizes DNA from RNA. Unlike typical bacterial defenses that degrade viral DNA, this system uses DNA synthesis, which was initially confusing.

To investigate this defense mechanism, Tang developed a novel technique to identify the DNA produced by reverse transcriptase. The DNA was long and repetitive, derived from multiple copies of a short RNA sequence. This RNA forms a loop, and the reverse transcriptase repeatedly moves around the loop to produce the repetitive DNA. Initially, the researchers questioned their results, suspecting an error, but it was later confirmed that this DNA forms a fully functional, free-floating gene.

The protein produced by this gene, named Neo, is crucial for the bacteria's antiviral defense, blocking viral replication and preventing the infection of other cells.

If similar extrachromosomal genes are found in humans or other higher organisms, it could revolutionize our understanding of genetics. These genes might not be located in the 23 human chromosomes but could be produced in specific conditions, providing essential information for normal physiology.

The research team is now applying their methods to search for human extrachromosomal genes created by reverse transcriptases. With thousands of reverse transcriptase genes in the human genome, many still have unknown functions, potentially uncovering new aspects of genetics.

New gene-editing techniques that combine CRISPR with reverse transcriptase are enhancing gene-editing capabilities. The reverse transcriptase used to create Neo has unique properties that might improve genome editing and gene therapy. Bacteria may hold a wealth of reverse transcriptases that could lead to new technologies once their functions are better understood.