The turn of the worm

Like any adolescent, the cotton bollworm has a tendency to wreak the maximum amount of havoc possible. Everything on a crop that is important to humans, it likes to eat: the boll of cotton plants, where the cotton fibre is produced; the head of corn, where it finds the juicy kernels; the fruit of the tomato plant, which needs no explanation.

Catholic in its tastes, it will go after “anything that’s green and vertical”, as Professor Phil Batterham puts it, in the process causing an estimated $5 billion in damage worldwide, every year.

After many years of trying, however, the genome of the cotton bollworm is about to be sequenced. In a multidisciplinary initiative, the CSIRO and the University of Melbourne are leading a global project to sequence the genome of Helicoverpa armigera, and to do a light coverage of some of its relatives, including Helicoverpa zea, its American cousin.

H. armigera is found in Australia, Asia, southern Europe and Africa; H. zea is found in North and South America. Together, the moth inhabits any part of the globe that is vaguely warm and therefore agriculturally significant, Batterham says.

Indeed, the two species are so closely related that many argue they are one – if they are crossed, their progeny is fertile, fulfilling the biological species concept.

Genetic analysis, however, is showing a few differences, and while they might not yet be different species, they are probably well on their way to being so, Batterham says.

“They are very closely related so anything you learn about the genome of one of the species is immediately applicable to the other. Furthermore, there are a number of other Helicoverpa species that are also pests, so what you really have is a cluster of pest species.”

Batterham, a geneticist from the University of Melbourne, is a well-known figure on the Australian genomics scene, both as the head of the Centre for Environmental Stress and Adaptation Research (CESAR) and as convenor of the Australian Genome Alliance.

He was one of the primary forces behind pushing for Australia to conduct a genome sequencing project – any genome sequencing project, to be fair – which eventually resulted in the Tammar wallaby consortium.

Although he rejects any credit for any role in that project getting up, anyone who has met him will know just how dear to his heart the Helicoverpa project is, promising as it does incredible insight into one of the world’s most destructive agricultural pests but also many downstream benefits that few in government, the public or perhaps even the wider scientific community understand.

“I had previously put to the Federal Government, as convener of the Australian Genome Alliance, a proposition that Australia invest in genomics as a starting point for research pipelines that could deal with significant issues for Australia,” he says.

“The previous government bypassed all opportunities to take that up and I hope that with the drop in sequencing costs we could really do something significant now as a country, to take control of our biodiversity and to use it. I’m hoping that this project will actually be the first of many.”

---PB--- Caterpillar genes

The two key partners in the Helicoverpa project are the Batterham’s team from the University of Melbourne and the CSIRO Division of Entomology, in particular the chief scientist in that division, Dr John Oakeshott, who worked on the Honey Bee Genome project, and another scientist in the division, Dr Karl Gordon, who has described telomeres and identified the gene for telomerase in honey bees.

While this project is almost exclusively Australian funded – and, scientifically, Australia is taking the lead – we can’t actually do it all alone and nor do we want to, Batterham says.

Other partners include a team led by David Heckel from the Max Planck Institute for Chemical Ecology and another team from INRA, the National Institute for Agricultural Research in France, led by Rene Feyereisen.

Feyereisen has already done some sequencing of the Helicoverpa genome, information that will be used in piecing it all together.

The bulk of the sequencing work will be done by Richard Gibbs’ team at Baylor College of Medicine’s Genome Centre, which has worked on the wallaby, the platypus, the cow, the human and a large number of insects.

Batterham says most of the sequencing will be devoted a deep and thorough job on Helicoverpa armigera, but a light coverage will also be done on a number of other Helicoverpa species.

“So far we’ve got 3.6-fold coverage of the genome,” he says. “That means we already have some sequences of probably almost every gene in the genome but the sequence is all in pieces. There are probably roughly around 14 or 15,000 genes in this genome – we’ve got a piece of all of them, but we can’t piece together whole genes yet and we can’t piece all of the genes together yet until we finish the sequencing.

“We are doing light coverage of other species and we are also doing very detailed analysis of genes that are expressed in key tissues. For example, the mid-gut of an insect is really important – that is where a lot of the metabolism of a lot of insecticide occurs, and that is where some of the primary targets might be found, because if you want to use insecticides, the protein that they are going after needs to be in tissues that the insecticide will reach.

“So the mid-gut is always considered to be a good target tissue, but we’ll look at a range of tissues to see which genes are expressed there and we’ll also look at the expression of genes throughout development, because some stages of development are clearly more important – the caterpillar is the most important.”

---PB--- Resistance

Batterham says one of the main aims is to find novel targets and proteins that the cotton bollworm produces that others don’t, or that are significantly different in this organism to others, to which new insecticides can bind.

One of the main problems with the pest is that it is resistant to nearly every class of chemical pesticide. Because proteins may be different or unique in this insect, it is hoped that the development of a targeted insecticide will calm fears of killing other organisms in the environment.

“I also want to understand the defence systems, because these organisms have very sophisticated defence systems, enzymes that can break down chemicals. And sometimes these enzymes are able to break down lots of different chemicals and so pose an ongoing threat.

“We need molecular markers to know where this moth comes from and goes to. If it can use a hundred different fruit, if it is so polyphagous, so catholic in its tastes, then we need to understand where it is moving to.

“Is it moving from one crop to another, is it moving from one area to another? How big is the population? Is Australia a whole population? Is the whole world a population? We need to understand that because if you don’t know where it comes from and goes to you can’t control it at the source.

“And we need to understand the relationship between this organism and its plant hosts. Why is it so darn good at using so many different plants?”

The first step is to do the deep sequence, a process which is underway now and is hoped to be complete later this year. Once that is done, the job of stitching the information together to see how the genes are aligned begins, followed by a deeper analysis of individual types of genes, and then the fun starts with the biology, Batterham says.

“It takes a long time, but I think there will be some benefits quickly. Our capacity to track this moth – we’ll have tools to do that within a year, good tools. But with novel pesticides, that might be 10 years out, but the benefit will roll out over the next one to 10 years.

“But what is really important is that that genome sequence is forever – we’ve done so those benefits will be in perpetuity. We will always have the capacity to intelligently control this moth, rather than what we’ve done in the past which is shooting shots in the dark, not knowing what we were really shooting at.”