Antagonistic genes control rice growth

Scientists at the Carnegie Institution, with colleagues, have found that a plant steroid prompts two genes to battle each other – one suppresses the other to ensure that leaves grow normally in rice and the experimental plant Arabidopsis thaliana, a relative of mustard. The results, published in the December 15, 2009, issue of The Plant Cell, have important implications for understanding how to manipulate crop growth and yield.

In plants, steroid levels reflect environmental and internal signals and control many processes. Steroid hormones called brassinosteroids (BRs) start their action on the surface of the cell and, through a molecular relay, send signals into the cell's nucleus to turn on or off specific genes, particularly those that are critical to regulating plant growth and development.

Dark solution to Darwin's mystery

A solution to Darwin's 'mystery of the mysteries' emerges from the dark matter of the genome

Biological species are often defined on the basis of reproductive isolation. Ever since Darwin pointed out his difficulty in explaining why crosses between two species often yield sterile or non-viable progeny (for instance, mules emerging from a cross between a horse and a donkey), biologists have struggled with this question.

New research into this field by basic scientists at Fred Hutchinson Cancer Research Centre, published online Oct. 22 in Science Express, suggests that the solution to this problem lies within the "dark matter of the genome": heterochromatin, a tightly packed, gene-poor compartment of DNA found within the genomes of all nucleated cells.

"Speciation is one of the most fascinating, unsolved problems in biology," said Harmit Malik, Ph.D., an associate member of the Hutchinson Centre’s Basic Sciences Division and corresponding author of the paper.

Malik and first author Joshua Bayes, Ph.D., a former graduate student in the Malik lab, focused on understanding the cellular function of a particular fruit fly (Drosophila) gene dubbed Odysseus. The gene is so named because of its ability to cause havoc and male sterility when introduced into the genome of another species. Odysseus is a gene that is derived from a transcription factor, and it was long believed to be a protein that turned on expression of other genes in Drosophila testis.

Odysseus also had been previously shown to rapidly evolve in its DNA-binding domain.

Based on this observation, Bayes and Malik reasoned that Odysseus must interact with some rapidly evolving DNA in the genome. They tested the hypothesis, first proposed by Malik and Hutchinson Centre colleague Steven Henikoff, Ph.D., that such hybrid-sterility proteins may bind repetitive satellite DNA in heterochromatin. Such repeats are believed to evolve rapidly due to an "arms-race" for preferential transmission during the process of forming an egg, whereby only one of four chromosomes is non-randomly chosen to be included into the egg.

Consistent with this hypothesis, Bayes found that Odysseus proteins localize to heterochromatic DNA found next to centromeres and on gene-poor chromosomes, which leads to their decondensation. Dramatically, the hybrid-sterility-associated Odysseus from one species showed additional localization to the Y chromosome of the other species.

Through experiments in cell lines and transgenic flies, Bayes further showed that Odysseus localization has rapidly evolved during recent evolution, evidence of the "arms-race" that drives rapid evolution of satellite DNA repeats. Altered expression and localization has profoundly deleterious consequences for the process of sperm formation, a process that remains a mystery and is under active study in the Malik lab.

The finding that rapidly evolving heterochromatin may underlie this phenomenon also ties in with other work in Malik's lab that explores how "mismatches" originating from rapid evolution of DNA and proteins could lead to chromosome segregation defects and aneuploidy events that are sometimes precursors in transitions to cancer.

Will genomics help prevent the next pandemic?

This week, the Public Library of Science, an open-access publisher, presents the "Genomics of Emerging Infectious Disease," a collection of essays, perspectives, and reviews that explores how genomics – with all its associated tools and techniques – can provide insights into our understanding of emerging infectious disease.

As pandemic H1N1 2009 influenza (commonly referred to as swine flu) continues to spread around the globe, people want to know if this flu poses more of a threat than other seasonal flu strains, how fast it's spreading (and where), and what can be done to contain it. The increasing speed at which complete genome sequences and other genome-scale data can be generated provides tremendous opportunities to address these questions by identifying the molecular changes in disease agents such as influenza viruses that will enable us to track their spread and evolution and to generate the vaccines and drugs necessary to combat them.

The "Genomics of Emerging Infectious Disease" collection discusses the challenges involved and how scientists and public health professionals might take advantage of these opportunities and advances to prevent the next pandemic.

Emerging infectious diseases are caused by a wide range of organisms, but they are perhaps best typified by zoonotic viral diseases, which cross from animal to human hosts and can have a devastating impact on human health. These zoonotic diseases include monkeypox, Hendra virus, Nipah virus, and severe acute respiratory syndrome coronavirus (SARS-CoV), in addition to influenza A and the lentiviruses (HIV) that cause AIDS. As Albert Osterhaus and colleagues from the Erasmus Medical Centre, Rotterdam, The Netherlands, point out in their article in the collection, the apparent increased transmission of pathogens from animals to humans over recent decades can be attributed to the unintended consequences of globalisation as well as environmental factors and changes in agricultural practices.

Articles in the collection also shine a spotlight on specific pathogens, some familiar and widespread, such as the influenza A virus, some "reemerging," such as the Mycobacterium tuberculosis complex that causes tuberculosis, and some identified only relatively recently, such as the bacterium Helicobacter pylori, which is associated with peptic ulcers and gastric cancer.

Others discuss the broader implications of genomics research in this area, such as what it means for researchers in developing countries or for our biosecurity. As Jacques Ravel and colleagues from the US University of Maryland School of Medicine note, genomics can and should be used proactively to build our preparedness for and responsiveness to biological threats.

The collection is a collaborative effort that combines financial support from Google.org [http://www.google.org/predict.html] with PLoS's editorial independence and rigor and the expert opinion of leading researchers from several different disciplines.

Rajesh Gupta from Stanford University, and colleagues provide Google.org's perspective and vision for how systematic application of genomics, proteomics, and bioinformatics to infectious diseases could predict and prevent the next pandemic. To realise this vision, they urge the community to unite under an "Infectious Disease Genomics Project," analogous to the Human Genome Project.

Jonathan Eisen, a Professor at the University of California, whose laboratory is in the UC Davis Genome Centre, is the Editor of this PLoS collection, which includes 14 articles – all publishing on 26 October 2009 – from six different PLoS journals (PLoS Biology, PLoS Medicine, PLoS Computational Biology, PLoS Genetics, PLoS Neglected Tropical Diseases, and PLoS Pathogens), reflecting the multidisciplinary nature of the topic.

Many scientific journals produce special issues on a topic of interest for their audiences. However, open-access publishing, such as that done by the Public Library of Science, makes it possible to have such a large multidisciplinary cross-journal collection simultaneously available online for unrestricted reuse, regardless of venue.

As outlined in the collection's editorial published in PLoS Biology, this collection will add to other "open science" activities that have helped provide insights into infectious disease more quickly than would have been thought feasible only a few years ago.

The faster, cheaper, and more openly we can distribute the discoveries of science, the better for scientific progress and public health. Managing the threat of novel, re-emerging, and longstanding infectious diseases is challenging enough even without barriers to scientific research.

Establishing standard definitions for genome sequences

Patrick Chain. Photos: DOE Joint Genome InstituteIn 1996, researchers from major genome sequencing centers around the world convened on the island of Bermuda and defined a finished genome as a gapless sequence with a nucleotide error rate of one or less in 10,000 bases. This effectively set the quality target for the human genome effort and was quickly applied to other genome projects. If a genome sequence didn't meet this stringent criterion, it was simply considered a "draft."

More than a decade later, researchers are finding that with the advent of the latest sequencing technologies the terms "draft" and "finished" are no longer sufficient to describe the varying levels of genome sequence quality being produced. The quality issue is of particular concern for any researcher who wants to use the sequence, in order to know its integrity and reliability. This is of even greater concern for reference genome sequences, such as those genome projects conducted in support of the US Department of Energy (DOE) missions of bioenergy and environmental clean-up, because they provide the foundational knowledge of the gene content and how these organisms interact with the environment.

As the proverbial "fire hose of data" becomes a Niagara torrent, with conservative estimates of 12,000 draft genomes hitting the public databases by 2012, researchers may be surprised to find that these datasets describe genomes that are not complete.

Recognising the problem, a group of researchers from several sequencing centers, including the DOE Joint Genome Institute (JGI), the Sanger Institute and the Human Microbiome Project (HMP) Jumpstart Consortium sequencing institutes, has proposed a new set of standards that expand upon the so-called "Bermuda standard." In the October 9 issue of the journal Science, they propose four additional categories between "draft" and "finished" status that reflect varying levels of completeness.

Organisers of the 2009 "Sequencing, Finishing, Analysis in the Future" meeting held in May at Santa Fe, N.M. Left to Right: Michael Fitzgerald, Broad Institute; Patrick Chain, DOE JGI; Bob Fulton, Washington University in St. Louis; Donna Muzny, Baylor College of Medicine; Johar Ali, Ontario Institute for Cancer Research; Chris Detter, DOE JGI; and Alla Lapidus, DOE JGI."In the past we've been limited to two options, requiring us and the other centers to come up with internal definitions," said DOE JGI metagenomics researcher Patrick Chain at Los Alamos National Laboratory (LANL), first author of the Science paper. "But these are not clear and they're not propagated to the databases to which we submit sequences. So when users try to download genomes they get data of unknown quality with no information, or a complete genome that they assume has been checked for missing-data errors."

Chain said that when he and the other organisers of the Sequencing, Finishing, Analysis in the Future meeting hosted by LANL first gathered in 2005, they were concerned by the varying quality of the new genomes being submitted to public archives . As the meeting organisers all represented major sequencing centers (and smaller groups as well), the genome projects standards group was initiated at LANL, stimulated by these concerns.

The six categories defined by the group include:

"Standard draft," which is the minimum amount of information needed for submission to a public database;

"High quality draft," which is typically generated by large sequencing centers such as DOE JGI, and which has little or no manual review;

"Improved high quality draft," which consists of data reviewed by either people or machines to some extent so most of the genetic data is assembled correctly, but some errors may still be present;

"Annotation-directed improvement," which is a sequenced segment that presents all the information in various gene regions as accurately as possible;

"Noncontiguous finished," which includes sequences that have been reviewed by both people and machines and would be considered complete except for "recalcitrant regions" that are proving problematic;

"Finished," which defines complete sequences that have minimal errors, if any.

DOE JGI's Chris Detter, one of the paper's senior authors, and head of the LANL Genome Science group, said that the definitions provided in the Science paper are fairly flexible because the group wanted the proposed standards to apply regardless of the genome project or sequencing technologies employed.

"My hope is all the major genome centers and advanced genomics groups use the gradations that fit their needs," he said. "Some centers may want all six, while some may only want three, but as long as they keep them intact we are in good shape. Then, my hope is that the smaller genomics groups adopt the classes as written to help the rest of the scientific community know what they are generating and submitting."

Chain added that the process of coming up with the proposed standards was not exactly an easy task since all major centers "have different pipelines, different sequencing techniques, different internal standards". They also recognised that the attempt to develop a "one size fits all" set of standards is still a work in progress. The definitions provided in the Science paper are fairly flexible, designed to apply regardless of the genome project or sequencing technologies employed and to meet each group's needs.

"We do expect that a number of people will comment on these standards, and possibly expand on the categories," he said, "but we feel we've covered all the bases with these six categories."

Chain said the group plans to team with the Genomic Standards Consortium, a grassroots movement begun by scientists who were concerned about the need for data collection standards in genome projects. The group has also talked to public archives such as GenBank to append these proposed standards to GenBank entries so that researchers can tell if the sequences will be useful to them. "Standards are a major issue to be tackled in genomics right now," Chain said. "These proposals are guideposts meant to inform users and generators."

Genomics science guarantees better winemaking

Photo: Kelly NigroWhile the art of fine winemaking is a beautiful thing, winemakers are increasingly turning to the power of science to give them the tools they need to ensure a high quality pour each and every time.

Thanks to innovative new research funded by Genome Canada and Genome British Columbia, help is on the way.

The research will harness the power of genomics to unlock fundamental gene functions within grapevine and yeast cells, ultimately helping growers and winemakers to improve wine production techniques and enjoy valuable cost savings in an industry that has seen USD4.2 billion in sales in Canada alone.

Dr. Steven Lund of UBC is one of the lead investigators on the USD3.4 million project, entitled “Grape and Wine Genomics.”

His work will focus on using genomics to identify protein biomarkers that will assist viticulturists to monitor how the vine and berries respond to natural and human-made environmental changes.

“Essentially, we are trying to put more advanced tools into the hands of producers,” says Lund, who equates current knowledge of the berry to a bit of a black box.

Currently, growers monitor what is happening in the berry like measuring pH and sugar levels to estimate harvest date, but not until late in the growth process. But there are currently no means to monitor the impact that management techniques such as fertilisation, irrigation, and leaf thinning have on berry ripening and flavour development earlier in each season.

“All of these techniques affect flavour and amino acid composition, but growers have no idea how or why,” says Lund. “That's where genomics comes in.”

The ultimate goal? “A practical application, a handheld device, which will help growers monitor proteins in the vine or berry at any time during any given season to determine when specific management practices should be applied and, perhaps most importantly, to what degree,” says Lund.

As such, Lund is collaborating with Dr. Paul Yager, Professor of Bioengineering at the University of Washington, whose team has created a portable device for detecting blood-borne pathogens. Yager will work with Lund to adapt his technology for use in the vineyard, directly on the vines.

But while high quality grapes are essential for a good glass, they are but one piece of the puzzle. The rest of the magic occurs during the winemaking process itself.

Dr. Hennie van Vuuren, the project's other lead investigator, is the Director of the UBC Wine Research Centre. His team, which includes scientists from the Max Planck Institute in Germany and Harvard University in the US, is studying the function of the Fermentation Stress Response genes in wine yeasts, which are added to the grape juice during the winemaking process and are essential for converting sugars into alcohol and flavour compounds.

Stress conditions

Van Vuuren and his team are using advanced technologies to see how yeast cells adapt to the many stress conditions they encounter, such as osmotic pressure, nutrient limitation, and increasing ethanol.

“We have recently discovered that yeast cells adapt to wine making stress conditions by switching on 62 genes of unknown function,” says van Vuuren. “Our objective is to discover function for each of these 62 genes, and in so doing, help winemakers to control their outcomes a little better.”

Cost savings is another important issue. Winemakers waste a lot of money due to spoilage caused by yeasts that are essentially faulty and don't allow them to achieve a fully dry wine. “Residual sugars are acceptable in varieties such as Riesling, but in a Cabernet Sauvignon for example, they will ruin the batch,” says van Vuuren, who also notes that the residual sugars can leave the wine susceptible to microbial spoilage.

The Grape and Wine Genomics project will also probe social science questions raised by the research. Dr. David Laycock is part of a team of five political scientists from Simon Fraser University, who are studying the social, political and regulatory contexts for scientific innovation as they relate to the wine industry.

Their work will help the Canadian industry and regulatory bodies better understand public concerns regarding the use of genomics technologies in the production of wine and the general food industry, and will help guide the responsible introduction of genomic technologies over the long term.

“Canadian industry can learn lessons from other wine producing countries and their attitudes towards scientific innovation,” says Dr. Laycock. “The best science and government funding in the world can still run up against a brick wall if there isn't a receptive public environment and an intelligent regulatory framework.”

“We are proud to support this innovative and valuable research, which positions BC and Canada as global leaders in genomic wine research,” says Dr. Alan Winter, President and CEO of Genome BC. “The knowledge that this team will generate will benefit wine producing countries around the world.”

Coral to be part of genome project

Photo: FishonlineOne of the corals that form the backbone of the Great Barrier Reef (GBR) is to become the first complex animal to have its genes fully explored in Australia.

Plans to sequence the entire genome of Acropora millepora, a branching coral whose “staghorn” shape and beautiful colours are familiar to millions of visitors to the GBR, marks a major milestone in Australian biotechnology: it will be the first animal genome to be fully sequenced and assembled in this country.

The mapping of the coral genome is a joint undertaking by the Australian Genome Research Facility (AGRF) and researchers in the ARC Centre of Excellence for Coral Reef Studies (CoECRS) based at James Cook University and the Australian National University. Experts from other Australian research institutions including The Walter and Eliza Hall Institute and The University of Queensland will also be actively involved in project design, assembly and annotation of the genome.

“It’s a genuine first for Australian science. For years we have been looking on while overseas countries explored the genetic potential of our iconic native species. Now at last we have a genome project that is 100 per cent Australian,” says Professor David Miller of CoECRS and JCU, who with Dr Eldon Ball at the ANU is co-leader of the project.

The staghorn coral may look like a simple animal, but its genome is surprisingly large and complex. In fact, David says, Acropora has around 20,000 genes – about the same number as man. Why such apparently simple animals as corals should require as many genes as humans is still unclear, but it was this coral which provided the first hints of the how genetically complex “simple” animals can be.

Comparing the new coral genome venture with the human genome project shows just how far and fast genetic technology has advanced. The human genome project cost over $US 2.7 billion and was a massive international collaboration, whereas with “next-generation” sequencing technology, the costs have dropped to a fraction of the price enabling genomic studies to be more generally accessible. The Australian research will be carried out using the latest technology developed by the biotech company Illumina which is both fast and cost effective.

“Acropora millepora, is already the best-characterised coral at the molecular level and has yielded important insights into the evolution of all animals,” David explains. “Corals are among the simplest animals and may reflect the ancestral animal condition and reveal important features of genome evolution.”

As to why a coral has been chosen as the first Australian animal to be gene mapped by Australian scientists, David Miller explains: “Corals have iconic significance for Australia. We have the best-preserved coral reef system in the world and the Great Barrier Reef is a cornerstone of a $6 billion a year tourist industry. As reefs elsewhere in the world decline, this value will grow if we can keep our reefs healthy and intact.”

“This gene mapping project has both practical and scientific significance. It will help us to understand how corals build reefs – and why they fail to do so when they are under stress.

“It will enable us to predict with much greater confidence how corals are likely to respond to changes in the oceans such as global warming, acidification, the spread of coral diseases and various forms of pollution.”

While they don’t much resemble us, corals lie deep on the ancestral tree of all animals and share many of our genes, David adds. The project is expected to provide significant insights into the mechanisms that underlie the evolution of life on earth, including of the branch leading to the higher animals and humans.

Shrinking mammal genomes

Evidence buried in the chromosomes of animals and plants strongly suggests only one group -- mammals -- have seen their genomes shrink after the dinosaurs' extinction. What's more, that trend continues today, say Indiana University Bloomington scientists in the first issue of a new journal, Genome Biology and Evolution.

The scientists' finding might seem counter-intuitive, given that the last 65 million years have seen mammals expand in diversity and number, not to mention dominance in a wide variety of ecological roles. But it is precisely their success in numbers that could have led to the contraction of their genomes.

"Larger population sizes make natural selection more efficient," said IU Bloomington evolutionary biologist Michael Lynch, who led the study. "If we are correct, we have shown how to bring ancient genomic information together with the paleontological record to learn more about the past and the present"

Lynch says the data he and his colleagues analysed suggest human genomes are still undergoing a contraction -- though you shouldn't expect to see noticeable changes in our chromosomes for a few million years yet.

Lynch's group examined the genomes of seven mammals, eight non-mammalian animals and three plants, specifically with regard for the long terminal repeat (LTR) sequences of transposable elements, a curious sort of "jumping" genetic sequence initially dropped into genomes by viruses. IU School of Informatics (Bloomington) bioinformaticians Mina Rho and Haixu Tang oversaw the survey of mammalian and non-mammalian genomes.

Transposable elements often lose their functionality soon after insertion but nevertheless are disturbingly common. In the human genome, for example, transposable elements constitute as much as 45 percent of an individual's total DNA. Long terminal repeat sequences, part of that figure, make up about 8 percent of humans' total DNA.

LTRs come in a range of sizes and ages, and it is the age distribution of LTRs that interested Lynch and his colleagues.

"This study started out as independent observations in the literature," Lynch said. "The data we saw suggested a bulge in age distribution of transposable elements in humans and mouse."

Left enough time, Lynch says, transposable elements are eventually lost from the genome, sometimes by accident and sometimes, perhaps, as the result of natural selection against excess DNA. An LTR is far more likely to survive a few years of cell divisions -- and the chance of obliteration via a DNA replication error -- than 10 million years of cell divisions. Plotting the full range of 17 species' LTRs, young and old, Lynch and his colleagues usually saw a descending curve with lots of new transposable elements and a dramatic drop-off in the number of older elements.

But not in most mammals. In humans, macaques, cows, dogs and mouse, Lynch's group observed a hill-shaped curve, with a peak of middle-aged LTRs and drop-offs both in the number of older and younger LTRs. The shape of the curve is consistent with previously published data for other types of so-called "junk" DNA elements.

The depressed numbers of very young LTRs, Lynch says, strongly suggests a contraction in overall genome sizes of the lineages of the mammals the scientists studied. That could come about in one of two ways, he says. One possibility is an increase in the efficiency of natural selection that accompanies population growth.

"We think that's the most likely explanation," Lynch said. "Another possibility is that natural selection was just stronger, but we doubt it. For that to be the case, natural selection would have to act in the same way on several lineages around the globe simultaneously."