Researcher Traces Gene Development In "Last Common Link"; Two Genes Diverge From One

Jeremy Gibson-Brown, Ph.D., assistant professor of biology at Washington University in St. Louis, studies amphioxus, a small marine worm, a primitive invertebrate species that is the closest living invertebrate related to vertebrates like ourselves. Gibson-Brown has found that a gene involved in the development of a body layer in invertebrates duplicated within the vertebrate lineage after the development of amphioxus.

However, in vertebrates, this gene, AmphiEomes/Tbr1, gave rise to two genes, Eomesodermin and T-brain-1, involved in brain development. While the vertebrate Eomesodermin gene has retained its original function in forming the mesoderm, or "middle skin" layer,in all vertebrate studies from fish, to amphibians to humans, the duplicate copy has lost that function and instead has evolved a role in forebrain development.

"This shows us how ‘old’ genes can give birth to new ones, and how the origins of novel developmental functions can be traced," said Gibson-Brown, who will have his results published in a forthcoming issue of the Journal of Experimental Zoology. His next step will be to look for these genes in lampreys, primitive jawless fish similar to the ancestors of later vertebrates.

"I want to see whether this gene duplication predated the separation of jawless fish and vertebrates and whether the role in forebrain development had yet been acquired."

Fruit flies, mice, worms and apes share an amazing amount of genetic information with us humans and with each other. For instance, there is only one-tenth of one percent genetic variation between a human and a chimpanzee.

A field of research has arisen to address what kinds of genetic change over time have occurred in different species to account for so many physical differences despite such genetic similarity. It is called evolutionary development.

"Evo-devo," as Gibson-Brown affectionately refers to this budding discipline, combines the principles of traditional evolutionary and developmental biology in examining the change in gene sequence and regulation that over time lead to the development of new species and eventually new body plans.

"We seek to unravel the history of the evolution of developmental programs in animals," Gibson-Brown explained. Gibson-Brown is studying the evolution of T-box genes, a group of genes that encode transcription factors regulating gene expression in embryogenesis, or the development of embryos.

Simply put, T-box genes control when and where a particular gene is turned on (expressed) or turned off during the course of an animal’s development. The vast diversity of body plans seen in animals alive today — and those who have lived in the past — are due in part to different expression patterns of these genes. T-box genes are present both in vertebrates and invertebrates, and so offer valuable insight into the emergence of new developmental programs, and hence new body plans, during the course of evolution.

Amphioxus is a small marine worm, a primitive invertebrate species whose last common ancestor with humans lived 600 million years ago. Amphioxus is the closest living invertebrate relative to the vertebrates, making it a very attractive target for Gibson-Brown’s research. He is interested in how these T-box genes, present in Amphioxus, humans and everything in between, have adapted their function and expression patterns to yield such a vast array of body plans, from worms to mice to humans.

"What I’ve been looking at is where and when these T-box genes are expressed in the development of amphioxus in order to understand the function of those genes in the last common ancestor of amphioxus and humans," Gibson-Brown said.

He has just begun work with lampreys, a very primitive vertebrate and one of the last species of jawless fish still alive today. Because lamprey ancestors evolved relatively shortly after the divergence of vertebrates from invertebrates they provide the next stepping stone in the story of T-box gene evolution.

By comparing the expression of T-box genes in Amphioxus, lamprey and mice, Gibson-Brown hopes to better understand the role that changes in gene regulation have played in the evolution of T-box genes.

"I want to understanding the regulatory elements controlling the expression of T-box genes in different species because the evolution of new developmental functions by genes is primarily achieved by the evolution of regulatory elements," he said.