New research from the University of St Andrews has discovered a crucial piece in the puzzle of how all animals with a spine - including all mammals, fish, reptiles and amphibians - evolved.
In a paper published today (2nd February) in BMC Biology, researchers found an intriguing pattern of gene evolution which appears to be significant for the evolutionary origin and diversification of vertebrates.
All animals have major signalling pathways that their cells use to communicate with each other, which control things like how their embryos and organs develop. The signalling pathways are fundamental to animal development and are major targets in disease-causing mutations and for the development of pharmaceuticals.
Proteins at the base of these signalling pathways are crucial as they control the final output from them, like a traffic system, directing cells into specific responses and gene expression.
Researchers created new gene sequencing data in sea squirts, a lamprey and a type of frog. They found the genes that make these signalling output proteins have evolved in a distinctive way. The sea squirt is an invertebrate that helped to distinguish the change when moving from invertebrates to vertebrates. Lampreys are an early branch in the vertebrate group, which pinpoints that this change happened at the invertebrate-to-vertebrate transition.
Researchers used long-molecule DNA sequencing, which allowed them to distinguish the different transcripts from each gene. Long-molecule sequencing had never been done on the genes expressed in these particular animals before. Therefore, researchers were able to characterise the real range of the transcripts and proteins produced from these genes in vertebrate development for the first time ever.
Unlike the invertebrate sea squirt, the lamprey and frog made higher numbers of different forms of proteins from the individual signalling output genes, compared to all sorts of other types of genes.
This significant change with the evolution of vertebrates is very striking. Given the importance of these pathways in how animals decide what types of cells, tissues and organs to make, it is highly likely these proteins have had a major role in making vertebrates (animals with backbones) different and more complex than invertebrates.
It was very surprising to us to see how this small selection of very particular genes stands out in the way that they are behaving compared to any other sort of gene we looked at.It will be exciting to determine how these various different protein forms work in distinct ways to generate the diversity of cell types we now see in vertebrates."
Professor David Ferrier, lead author of the study, School of Biology, University of St Andrews
These diverse protein variations not only shed light on the origins of how we, and most other animals with backbones have evolved, but will also be important for future work on understanding how these proteins and pathways might be manipulated in disease management.
Source:
Journal reference:
Torres-Aguila, N. P., et al. (2026). Long-read sequencing reveals increased isoform diversity in key transcription factor effectors of intercellular signalling at the invertebrate-vertebrate transition. BMC Biology. doi: 10.1186/s12915-026-02522-w. https://link.springer.com/article/10.1186/s12915-026-02522-w