How jumping genes and RNA bridges promise to shake up biomedicine Premium

Discover the revolutionary world of transposons, 'jumping genes' that shape genetics and evolution, with potential for gene therapy.

The year was 1948. It had only been about half a century since scientists had rediscovered Gregor Mendel’s work on inheritance in pea plants. This year, a scientist working on the genetics of the maize plant would challenge the then prevailing concept that genes are stable and arranged in an orderly manner on the chromosome. Barbara McClintock at the Carnegie Institution found that some genes were able to move around within the genome. These genes were called mobile elements or transposons.

Prof. McClintock also made another significant observation: depending on where the mobile elements were inserted, they had the ability to reversibly alter gene expression. She used corn kernels’ colours as a surrogate to understand hereditary characteristics, and this way figured out transposons moved about in the genome of the maize plant. She was awarded the Nobel Prize in Physiology or Medicine in 1983 for this work.

Between 1948 and 1983, researchers found transposons in an array of life-forms, including bacteriophages, bacteria, plants, worms, fruit flies, mosquitos, mice, and humans. They were nicknamed ‘jumping genes’.

The discovery of transposons revolutionised our understanding of genetics, in particular their role in enabling nature’s wondrous diversity. Transposons influence the effects of genes by turning ‘on’ or ‘off’ their expression using a variety of epigenetic mechanisms. They are thus rightly called the tools of evolution, for their ability to rearrange the genome and introduce changes.

More than 45% of the human genome consists of transposable elements. Just as they create diversity, they also create mutations in genes and lead to diseases. However, most of the transposons have themselves inherited mutations and have become inactive, and thus can’t move around within the gnome.

Over the years, researchers have attempted to resurrect inactive transposons from the genomes of the animal kingdom, hoping that the results will be useful in biomedical applications like genetic correction to cure a disease or for gene therapy.

For example, in 1997, researchers studied the genomes of fish and reconstructed a transposon called ‘sleeping beauty’ at the molecular level. This transposon became dormant in vertebrates millions of years ago. The researchers elegantly reprogrammed the synthetic avatar to work in human cells. In future, a similar synthetic transposon inspired by nature may be able to turn off a problem gene or over-express another to accentuate some desirable characteristic.