A Small Genetic Shift May Have Launched Vertebrate Evolution

From frogs and fish to birds and humans, vertebrates span an enormous range of forms. They include animals with backbones, complex nervous systems, and specialized organs that distinguish them from their invertebrate relatives. How that transition unfolded at the genetic level remains an open question.

Now, researchers at the University of St Andrews report that a small group of genes behaved differently as vertebrates emerged. In a study published in BMC Biology, the team found that these genes, which help cells communicate during development, began producing a wider range of protein forms at that point in evolution. The change appeared specifically in genes that sit at the end of signaling chains, where they influence how cells decide what to become.

“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,” said lead author David Ferrier in a press release.

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The Role of Signaling Genes in Vertebrate Evolution

All animals rely on signaling pathways, networks of genes and proteins that allow cells to communicate. These pathways help determine how embryos develop and how tissues and organs form.

At the end of each pathway are transcription factor effectors, proteins that control how genetic instructions are carried out. They determine which genes are switched on or off in response to signals.

To see how this system changed over time, the researchers compared three species that sit at important points in evolution: a sea squirt, which represents an invertebrate relative of vertebrates; a lamprey, one of the earliest vertebrates; and a frog, a more recently evolved vertebrate. Comparing these species allowed the team to identify changes that appeared specifically at the boundary between invertebrates and vertebrates.

Expanding Protein Diversity

Vertebrates do not have many more genes than simpler animals. Humans, for example, have roughly the same number of genes as some invertebrates. That suggests complexity may depend less on adding new genes and more on expanding what existing genes can do.

Using long-read DNA sequencing, the researchers captured full-length versions of gene transcripts to see how many protein forms each gene produced. This allowed them to measure protein diversity in greater detail than had been possible before.

They found that in vertebrates, a small group of signaling genes generates many more distinct protein forms than it does in the sea squirt. This increase was not widespread across the genome. It was specific to these regulatory genes.

Having more protein variants may give developing cells more flexibility. Small differences in protein structure can influence how cells respond to signals and what types of tissues they form. Rather than inventing entirely new genes, early vertebrates may have broadened the range of functions carried out by genes they already had.

Implications Beyond Evolutionary History

The results suggest that expanding the range of protein forms in a small set of genes may have helped shape traits such as specialized organs and complex tissues.

These same signaling systems are active in human development and are often involved in disease. Learning how their protein diversity emerged could offer insight into how they operate today.

The next step is to determine how each protein variant functions during development. “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,” explained Ferrier.

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