IIT-Bombay Research: Tiny DNA Hitchhiker Outsmarts Yeast To Ensure Survival Across Generations
Mumbai: A team of researchers from the Indian Institute of Technology Bombay (IIT-B) has shed light on how a seemingly useless piece of DNA manages to outsmart yeast cells and ensure its survival across generations.
Published in a recent review, scientists Deepanshu Kumar and Professor Santanu Kumar Ghosh from the Department of Biosciences and Bioengineering at IIT-B detail the survival strategy of a small, circular DNA molecule found in yeast, known as the 2-micron plasmid. Despite constituting only about 0.25–0.37% of the yeast’s total DNA and offering no apparent benefit to its host, this “selfish” DNA has found a way to ensure its inheritance.
“Instead of floating freely and risking uneven distribution, the 2-micron plasmid has evolved a clever trick of hitchhiking,” explained Prof. Ghosh. “It attaches itself to the host cell’s chromosomes, ensuring it gets separated along with them during division.”
The research outlines how yeast, which reproduces by budding, duplicates its chromosomes before dividing. Similarly, the 2-micron plasmid duplicates itself, clustering into 3–4 tightly bound groups out of the 40–100 copies typically found in a yeast cell. These clusters remain evenly distributed only due to a sophisticated strategy involving two plasmid proteins—Rep1 and Rep2—and a protein complex from the host cell.
The IIT-B team discovered that only one version of a yeast protein complex, called RSC2, facilitates the plasmid’s attachment to chromosomes. “RSC2 interacts with both the Rep proteins and the cell’s division machinery, acting as a bridge to attach the plasmid to the chromosomes,” noted Prof. Ghosh.
Interestingly, the plasmid prefers to anchor itself to inactive regions of chromosomes, such as the ends and ribosomal DNA zones, which are compact and not heavily involved in protein production—an ideal spot for a genetic hitchhiker looking to stay out of sight.
Supporting proteins like cohesins and condensins—typically involved in chromosome separation—also join the plasmid’s ‘partitioning complex’, but only in the presence of Rep proteins. When these Rep proteins are missing or altered, the plasmid fails to distribute properly between cells.
“The exact role of cohesins and condensins in plasmid attachment to chromosomes is still unclear, but they may act as cementing agents that help keep plasmids attached,” Prof. Ghosh added.
The review also addresses the question of why evolution hasn’t eliminated the plasmid. The answer lies in its mimicry of chromosomes. “By hitchhiking along with the host’s chromosomes, the 2-micron plasmid avoids the metabolic cost of developing its own segregation mechanism,” said Prof. Ghosh. This deception makes the yeast cell incapable of identifying the plasmid as an invader, allowing it to persist harmlessly.
Interestingly, this hitchhiking mechanism is not unique to yeast. Similar strategies are used by certain viruses, including the human papillomavirus (HPV), which tethers its DNA to human chromosomes via viral proteins. The similarities suggest an evolutionarily conserved strategy and present new avenues for antiviral research.
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