In a paper appearing in the August 5 issue of the journal Nature, a team of researchers led by Daniel Rokhsar of the University of California, Berkeley, and the Department of Energy's Joint Genome Institute (JGI), report the draft genome sequence of the sea sponge Amphimedon queenslandica and several insights the genome gives into the origins of both the first animals and cancer.
All living animals are descended from the common ancestor of sponges and humans, which lived more than 600 million years ago. A sponge-like creature may have been the first organism with more than one cell type and the ability to develop from a fertilized egg produced by the merger of sperm and egg cells.- that is, an animal.
"Our hypothesis is that multicellularity and cancer are two sides of the same coin," said Rokhsar, program head for computational genomics at JGI and a professor of molecular and cell biology and of physics at UC Berkeley. "If you are a cell in a multicellular organism, you have to cooperate with other cells in your body, making sure that you divide when you are supposed to as part of the team. The genes that regulate this cooperation are also the ones whose disruption can cause cells to behave selfishly and grow in uncontrolled ways to the detriment of the organism."
As part of the new analysis, the team looked in the sponge genome for more than 100 genes that have been implicated in human cancers and found about 90 percent of them. Future research will show what roles these genes play in endowing sponge cells with team spirit.
Sponges are often described as the "simplest" living animals, while humans are considered relatively "complex," but how this differential complexity is encoded in the genome is still a major question in biology The new study shows that, while the sponge genome contains most of the gene families found in humans, the number of genes in each family has changed significantly over the past 600 million years. By analyzing which gene families were enriched or depleted in different groups of animals, the authors identified groups of gene functions that are associated with morphological complexity.
"The genome raises questions of what it means to be an animal," said first author Mansi Srivastava, a former UC Berkeley graduate student who now is a post-doctoral associate at the Whitehead Institute for Biomedical Research in Cambridge, Mass.
"Though we think of a sponge as a simple creature whose skeleton we take to the bathtub, it has a lot of the major biochemical and developmental pathways we associate with complex functions in humans and other more complex animals," she said. "But there are certain missing components. Future studies will reveal how sponges operate as bona fide animals without those components, and how the addition of those components led to the evolution of more complex animals."
Some of the missing components are involved in the cell cycle, the series of steps cells go through in order to divide. Among these is the enzyme family known as cyclin-dependent kinase 4/6 (CDK 4/6), which in mammals is crucial to transitioning between phases of the cell cycle. Though CDK4/6 was not found in the sponge genome, it is present in the sea anemone genome, raising the question of whether the appearance of CDK4/6 in the ancestor of "true" animals (eumetazoans) changed the animal cell cycle in a fundamental way. Inhibitors of CDK 4/6 halt the cell cycle and are used to treat breast cancer.
The authors also identified in the sponge many of the same genes that characterize all other animals: genes involved not only in cell division and growth, but also in programmed cell death; the adhesion of cells to other tissue and to one another, signaling pathways during development, recognition of self and non-self; and genes leading to the formation of different cell types.
What sponges lack, however, are a gut, muscles and neurons.
"This incredibly old ancestor possessed the same core building blocks for multicellular form and function that still sits at the heart of all living animals, including humans," said coauthor Bernie Degnan, a professor of biology at the University of Queensland, Australia, who collected the sponge whose genome was sequenced from the Great Barrier Reef. "It now appears that the evolution of these genes not only allowed the first animals to colonize the ancient oceans, but underpinned the evolution of the full biodiversity of animals we see today."
According to Degnan, essentially all the genomic innovations that we deem necessary for intricate modern animal life have their origins much further back in time that anyone anticipated, predating the Cambrian explosion by tens if not hundreds of millions of years.
"What marked the evolutionary origin of animals was the ability of individual cells to assume specialized properties and work together for the greater good of the entire organism. The sponge represents a window on this ancient and momentous event," said coauthor Dr. Kenneth S. Kosik, the Harriman Professor of Neuroscience at UC Santa Barbara and co-director of the Neuroscience Research Institute.
"Remarkably, the sponge genome now reveals that, along the way toward the emergence of animals, genes for an entire network of many specialized cells evolved and laid the basis for the core gene logic of organisms that no longer functioned as single cells," he said, "but as a cooperative community of specialized cells all geared toward the survival of a complex multi-cellular creature."
"The beauty of having this genome is that now we can ask about all known biological processes, and go through hundreds of genes to tell definitively whether or not our common animal ancestor had them or not," Srivastava said.
The sponge genome may also have more practical implications, according to Degnan.
"Sponges produce an amazing array of chemicals of direct interest to the pharmaceutical industry," he said. "They also biofabricate silica fibers directly from sea water in an environmentally benign manner, which is of great interest in communications. With the genome in hand, we can decipher the methods used by these simple animals to produce materials that far exceed our current engineering and chemistry capabilities."
The research was funded primarily by the Department of Energy through JGI and by the Australian Research Council.