Scientists crack the genetic code behind nature’s greatest transformation

The transformation of the walking caterpillar into a winged butterfly, known as metamorphosis, is one of nature’s greatest wonders. While the spectacle is well known, the molecular choreography behind this dramatic change has remained a mystery until now.

In a pioneering study, scientists at the University of Brighton have discovered the gene expression and chemical modifications of the caterpillar’s entire genome across every stage of its life cycle, from larva to a mature adult – revealing how it effectively amends the use of its own biological blueprint to become a butterfly.

Led for Brighton by Professor Rameen Shakur, Director of the Brighton Integrated Genomics Unit, the international research team observed how the caterpillar undergoes a complete internal reprogramming to become a butterfly. By analysing DNA and molecular signals, they found that the caterpillar switches off some genes it no longer needs, such as those for storing fat, and activates new ones for building strong muscles, rewiring the brain and producing the energy needed for flight.

Prof. Shakur said, “When I was a child, my mother read me the famous kids’ book The Very Hungry Caterpillar. I was captivated by the pictures of how a growing caterpillar then emerges as a butterfly from its cocoon. This idea of transformation stayed with me even as a clinician scientist. This study was born from that childhood curiosity.

“For the first time, we’ve captured metamorphosis at the level of the whole organism, not just isolated organs or partial snapshots. What we found is extraordinary. The caterpillar doesn’t just change shape - it completely rewrites its genome. That’s a profound lesson in adaptation and survival, with implications for everything from biodiversity to the way humans grow, repair and regenerate.”

Dr Andrew Hesketh, first author and senior bio-informatician from University of Brighton said, “We were able to use the very latest long read sequencing technology to identify methylation of individual DNA base pairs, and to sequence the complete range of intact RNA messages produced from genes. This allowed us to look at the splicing together of the different parts of every gene in the genome as it is transcribed, and to relate this expression to the effect of nearby DNA methylcytosine modifications.”

The study, published in Nature Scientific Reports, was co-led by Professor Patrícia Beldade from the University of Lisbon. She added that: “Most previous studies of butterfly metamorphosis focused on individual body parts, like wings or legs. By sequencing entire bodies across multiple stages, we captured the global reprogramming including splicing that orchestrates this iconic transformation.”

Beyond its scientific significance, the research arrives at a critical time for butterfly conservation. Butterflies are far more than a splash of colour in gardens and fields – they are key pollinators which help maintain plant diversity, which in turn supports insects, birds and mammals further up the food chain. Yet, more than half of Britain’s butterfly species have declined since 1976, with 2024 marking the fifth-worst year on record. Habitat loss, pesticide use, and climate change are accelerating their decline.

Habitat destruction, pesticide use, and increasingly erratic weather linked to climate change are pushing populations down faster than they can recover. Because butterflies react quickly to habitat loss and pollution, they serve as early indicators of environmental stress and climate change. This new genetic insight could help scientists understand how butterflies adapt and inform strategies to protect them.

But the implications go even further.

“Metamorphosis is a living model of whole-body transformation,” said Professor Shakur.

“Our work provides new insights for regenerative medicine, stem-cell research and developmental biology. Understanding how life edits and repurposes its genetic code could inform future therapies for human healing and growth.”

This landmark study provides a rare and dynamic view of metamorphosis at the organism level – and lays the foundation for deeper understanding of development, adaptation and regeneration across species.