One is a creature of the briny deep, a bizarre survivor of a long-forgotten era that holds clues to how our marine ancestors grew limbs and clambered onto land. The other is the bestriped occupant of household aquariums that could prove to be a valuable weapon against a range of genetic disorders.
Two fish with life histories so different they would never meet in the wild. Yet this week the ponderous coelacanth (SEE-lah-canth) and the perky zebrafish are sharing the scientific limelight. They are the latest in a growing club of species to have their complete genomes published – a sign of how crucial animal genomes are to understanding human origins and disease.
“We’re finding it’s very important to sequence other organisms, including strange ones, because it actually tells us about the human genome itself and about how evolution works,” said Jessica Alfoldi, a researcher at the Broad Institute in Cambridge, Mass., who was part of the coelacanth study.
The concept of a genome as a biological and commercial resource is evolving too. Earlier this week, the U.S. Supreme Court heard arguments in a case that may ultimately determine whether certain human genes that are relevant to disease can be considered intellectual property.
Yet the ability to read all the billions of base pairs that make up a human’s or another animal’s entire DNA sequence – an increasingly affordable option in research – is a development as potent as the discovery of the structure of DNA itself, which touched off the genetic revolution when it was first published 60 years ago this month.
What whole genome sequencing offers is ready access to the myriad of variations that distinguish the DNA of individuals and species from one another. By identifying and comparing those variations, researchers can hope to untangle the roles that individual genes play in biological function and development. This, in turn, can reveal the underlying causes of disease or expose the molecular markers that record the history of all life on Earth.
Taken together, the two fish genomes, both published Thursday in the journal Nature, are emblematic of this double power.
On one hand, the zebrafish is a go-to laboratory animal, often used in studies of cellular processes that are present in humans. Because they grow from externally fertilized eggs, zebrafish offer a quick and convenient way to watch how genes orchestrate the earliest stages of life.
“The rudiments of all their major organ systems are in place by 24 hours after fertilization – which is amazing,” said Ashley Bruce, a developmental biologist at the University of Toronto who works with zebrafish.
In contrast, the coelacanth could scarcely be a more challenging research subject. It belongs to a lineage that was believed to have disappeared along with the dinosaurs, until one was hauled up from South African waters in 1938. Living unseen at great depth, coelacanths do not survive being brought to the surface.
Yet they are biological superstars too, because they belong to the line that once gave rise to land vertebrates. In evolutionary terms, they are more closely related to humans than to zebrafish.
“Everyone is interested in how our aquatic ancestors developed this ability to crawl up on land,” said Chris Amemiya, an evolutionary biologist at the Benaroya Research Institute in Seattle, and lead author of the coelacanth genome paper.
In a first step towards an answer, Dr. Amemiya and his collaborators were able to identify an element of the coelacanth genome whose equivalent in humans gives rise to hands and feet. As to what that gene does in the coelacanth, “that’s the million-dollar question,” Dr. Amemiya said, and a starting point for future studies.
The zebrafish genome also marks a beginning rather than an endpoint, though it is the product of a nine-year effort. That includes work towards a systematic understanding of the roughly 26,000 zebrafish genes that serve as blueprints for producing specific proteins, 70 per cent of which have close human analogs.
For Derek Stemple of the Wellcome Trust Sanger Institute in London, one of the leaders of the zebrafish study, the payoff is the creation of a resource that researchers can turn to whenever a suspect gene is implicated in a rare disease.
“We can often disrupt the expression of that gene in zebrafish and find that it produces an effect that’s similar to what you see in humans,” Dr. Stemple said. Such studies offer the potential not only to confirm the cause of a disorder but a way to test treatments for it.
In a related article in Nature, Alexander Schier, a molecular biologist at Harvard, writes: “It is now obvious that the full impact of the human genome sequence was not apparent upon its release.”
As the two fish genome studies seem to demonstrate, we only get to the full impact of DNA sequencing when other species are along for the ride.