Feature: Illuminating coral

One doesn’t often associate the north of England with an abundance of tropical corals. Yet David Miller found himself drawn to them early in life while living in Salford, near Manchester. “My original inspiration to study biology was from seeing TV footage and a movie from Hans and Lotte Hass of Red Sea coral reefs,” says Miller. “I could not believe that I lived on the same planet as these beautiful and strange places.”

Some years later, with a PhD in microbial biochemistry and genetics from the University of Kent and a post-doc in biochemistry from the University of Bristol under his belt, Miller found himself in sunny Townsville, Queensland. “I arrived in Townsville purely by accident and rediscovered corals and coral biology,” he says. “When I came here was not long after mass coral spawning had been discovered. There was a lot of coral biology going on here, but no lab doing molecular genetics or genetics. It seemed like a logical place for me to plug in.”

And plug in, he did. Miller, now a professor at JCU, has worked on a wide range of projects in coral biology since his arrival 24 years ago, such as characterising various gene families in corals, and more recently, a number of express sequence tag (EST) projects. The latter led to a quite remarkable revelation that corals – simple animals though they are – have a genome about as complex as that of ‘higher’ mammals, including a lot of genes that were thought to have evolved long after the phyla to which they belong went their separate ways in their evolutionary history.

“Corals share many genes with vertebrates that are missing from the model invertebrates,” says Miller. “Those genes were thought to have been invented during vertebrate evolution to enable morphological complexity.”

Yet, there they were, in the morphologically simple coral, along with evidence to suggest that their presence was not due to lateral gene transfer. This discovery led to a much-discussed paper in Current Biology and reinvigorated the idea of ancestral genetic complexity: “the idea that the ancestor of all animals was quite complex and contained many genes, and what’s gone on since that time has been largely gene loss.”

Miller is now in the fortunate position to continue to feed his passion for corals and continue exploring the notion of ancestral genetic complexity by diving in to an ambitious new project: the sequencing of the entire genome of, Acropora millepora.

From this project, Miller hopes to not only learn more about the biology and intriguing evolutionary past of corals, but also contribute to the preservation of these wonderful creatures in the face of modern environmental pressures like coral bleaching.

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Illuminating the coral genome

The race is on to develop the first rapid, cost effective whole genome sequencing technology, and the stakes are high, with a multi-billion dollar industry up for grabs in the coming years. One of the major players in this race is the California-based Illumina, which is driving forward with the latest iteration of its popular Genome Analyzer technology, acquired from Solexa in 2006.

Miller has some experience working with Illumina technology from previous research, so when he heard that the Australian Genome Research Facility (AGRF) and Illumina were looking to promote genome science in Australia, he leapt at the opportunity to get on board.

“The AGRF and Illumina wanted to demonstrate that fairly complex animal genomes can be sequenced and assembled in Australia without a large budget, based on the Illumina technology,” he says. “With Acropora we’ve got a smallish genome, it’s the best characterised coral at the molecular level and we have previously worked with AGRF and have runs on the board using Illumina technology thanks to GeneWorks. Corals are also iconic for Australia. So we ticked most of the boxes.”

The result is the coral genome project, which is a collaborative venture between the AGRF, Illumina and the ARC Centre of Excellence for Coral Reef Studies (CoECRS). Miller will be working with Dr Eldon Ball, of the Australian National University, and Rob Saint, who was recently made Dean of Science at Melbourne University.

Dr Kirby Siemering at AGRF is heading up the sequencing and assembly of the genome along with Dr Annette McGrath, head of Bioinformatics at AGRF, and Sylvain Foret at JCU, Matthew Wakefield, Tony Papenfuss, who are members of Terry Speed’s group at the Walter and Eliza Hall Institute of Medicar Research, and David Edwards at the University of Queensland.

The long and the short

Miller and his team had a chance to try out next generation sequencing technologies from both 454 at the AGRF, and Illumina at GeneWorks when they were doing transcriptome characterisation, but the heavy lifting in this project will be handled by AGRF using Illumina’s latest Genome Analyzer IIx. “It’s fast and you get a massive amount of data for the money,” he says. “Compared to 454 you get 10-100 times the data per dollar with Illumina.

“But the downside is that reads are shorter. 454 reads are typically over 500 bases, whereas the available Illumina does 75 bases, although Illumina is talking about 100 bases within weeks or months. So far we’ve been really impressed by the quality of the data we’ve got using Illumina. And certainly the volume of data is just overwhelming.”

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After you get the mountain of data, you then need to put it all together. And having shorter reads makes that an even more daunting challenge. As for how long that will take, it all depends on how far McGrath and the Bioinformatics group at AGRF decide to push the assembly. “Genome projects are never really finished,” says Miller, “you just get better and better assemblies. But we don’t need a human genome type assembly. We just need a working assembly.”

The first round of sequencing is already done, but Miller anticipates they’ll need a second round, which should be completed this year. Then, all going well, the “final” (working) assembly should be available during 2010.

Simply complex and the payoff for coral biology

Despite the dazzling array of vast metropolises they construct and inhabit, corals are relatively simple organisms – about as simple as you can get for a true animal. It’s also one of the best characterised, but having the whole genome on hand will help answer some perplexing questions about coral, such as how they construct their skeletal homes. One way to do this is to compare the coral genome to that of its near relative, the sea anemone, which had its genome sequenced in 2006.

“There are of lots of interesting comparisons we can do,” says Miller. “These are fairly close evolutionarily – I always say sea anemones are corals without skeletons. So if you want to learn about what genes are required for coral specific traits, like building a massive skeleton, symbiosis and so on, that comparison is likely to be particularly informative.”

Corals are also potentially able to tell us a great deal about the original roles of many of the genes implicated in human disease. The fruit fly Drosophila has yielded powerful insights into the molecular bases of many human genetic disorders, but corals have more genes in common with humans than Drosophila, and human genes are often more similar to a coral gene than to their fly counterparts.

The coral genome will should provide insights into animal genome evolution, such as the notion of ancestral genetic complexity, but it also has many potential applications to coral biology. One example is a better understanding of the impact of climate change on corals. The genome sequence will enable unbiased screens for changes in the expression of every coral gene during heat stress or at elevated carbon dioxide levels. “With this knowledge in hard, we can then look at key loci to find alleles that correlate with tolerance, potentially enabling coral husbandry – farming corals to enable reseeding of damaged reefs,” says Miller.

Genomics holds great promise for the future of coral reefs, and the coral project represents a milestone in Australian biology. Australia enters the genomics club with an iconic species at a time when the future of coral reefs will be critically dependent on a better understanding of their molecular genetics.