The international team of scientists from Australia, Iran and Japan say there’s an estimated 35,000 proteins encoded by the rice genome sequencing, and yet we still don’t have experimental evidence for 82 per cent of them.
This is important because rice is the major food source for more than half the world’s population, and in order for it to grow in warmer climates and with less water we will need to better understand rice at the molecular level, which means carrying out genome sequencing.
“The genome of rice was completed and published in 2001,” says Professor Paul Haynes from Macquarie University, and a co-author of the new study. “So surely we know enough about it now that we should be able to manipulate how it grows to meet our needs? Well, we don’t.”
“What we have for rice, like most of the well-studied plant and animal species, is a good first approximation of what the gene sequence actually encodes for, but there is still a very large amount of information yet to be confirmed.”
Rice is Australia’s ninth largest agricultural export and generates approximately $800 million in revenue each year, but this productivity comes at a significant cost.
Australian farmers use large amounts of water to irrigate their crops. The increasing demand for this water is threatening the sustainability of their rice production.
“It is imperative that we find ways to make rice better adapted to environments with warmer climates and less available water,” says Paul.
One way to do this would be to give commercial rice varieties some of the characteristics of native Australian varieties of rice, he says.
These plants grow vigorously in many wild areas across Australian without additional watering, in part because their roots grow longer and penetrate deeper into the soil allowing the plants better access to underground reserves of both water and nutrients.
“If we could somehow transform commercial rice varieties so that they grow deeper roots, thereby increasing water uptake efficiency while still retaining high grain yields, we could produce more sustainable plants that would help to future-proof the Australian rice industry,” says Paul.
And that’s why finding rice’s remaining missing proteins and completing the genome sequencing is so critical.
Missing proteins are ones that appear to be encoded in the rice’s genes but have not been experimentally confirmed to exist in the rice itself.
The idea of missing proteins originally arose from researchers working on human genome sequencing, says Paul, but it’s equally applicable to important cereal crops like rice.
The Human Proteome Project is making a map of all the proteins encoded by the human genome, to advance the diagnosis and treatment of disease.
Paul’s team took a similar approach when they looked at rice.
Initially they found that 98.5 per cent of the proteins in rice are considered missing. However by mining publicly available datasets and matching this data with information from the rice genome they were able to reduce this percentage of missing proteins to 82 per cent.
“If we are to continue to feed the ever-increasing number of people on our planet, we really need to produce rice which is more sustainable in terms of better water use and better nutrient uptake, while still maintaining current levels of grain production,” says Paul.
“This will require us to understand rice at the molecular level in a way that we have never done previously.
“It is only by understanding in great detail what happens inside a particular cell that we can really understand what goes on at the whole organism level, and how we can potentially change how that particular organism responds to an external set of circumstances or stimuli.”
The team hopes this study will form the basis of a large-scale scale international collaborative project aimed at identifying all the remaining missing proteins in rice.
The study was published in Molecular Plant and co-authored by researchers from Macquarie University, the Agricultural Biotechnology Research Institute of Iran, the University of Tehran, and the University of Tsukuba.
Featured image above: The peanut (Arachis hypogaea L.) is an important global food source and a staple crop grown in more than 100 countries, with approximately 42 million tonnes produced every year. Credit: ICRISAT
In a world first, under the leadership of University of Western Australia Winthrop Professor Rajeev Varshney, a global team sequenced and identified 50,324 genes in an ancestor of the cultivated peanut, Arachis duranensis.
They decoded the peanut DNA to gain an insight into the legume’s evolution and identify opportunities for using its genetic variability.
Importantly, the researchers have isolated 21 allergen genes, that, when altered, may be able to prevent an allergic response in humans.
The last decade has seen an alarming rise in peanut allergies with almost three in every 100 Australian children suffering, and only 20 per cent growing out of the allergy.
“These 21 characterised genes will be useful in breeding to select the superior varieties in the laboratory such as ones that are non-allergenic,” Varshney says.
They also identified additional genes that would help increase crop productivity and improve peanut nutritional value by altering oil biosynthesis and protein content.
Peanuts or groundnuts (Arachis hypogaea L.) are an important global food source and are a staple crop grown in more than 100 countries, with approximately 42 million tonnes produced every year.
Originating in South America, humans have cultivated peanuts for more than 7,600 years.
With a very high seed oil content of 45–56 per cent, peanut oil contains nearly half of the 13 essential vitamins and 35 per cent of the essential minerals.
Peanuts are also associated with several human health benefits, and have been found to improve cardiovascular health, reduce the risk of certain cancers, and control blood sugar levels.
“This genome sequence has helped to identify genes related to resistance to different diseases, tolerance to abiotic stresses and yield-related traits,” Varshney says.
“By using this ’molecular breeding’ approach, we can also accelerate the breeding process, and generate superior varieties in 3–5 years compared to traditional breeding that takes 6–10 years.”
Varshney says genomics-assisted breeding is a non-GMO or ‘non-transgenic’ approach.
“This is basically a simple breeding process that uses the molecular markers/genes to select the lines in the breeding, and farmers have been growing such varieties for many crops all around the world,” Varshney says.
Since successful genome sequencing was first announced in 2000 by geneticists Craig Venter and Francis Collins, the cost of mapping DNA’s roughly three billion base pairs has fallen exponentially. Venter’s effort to sequence his genome cost a reported US$100 million and took nine months. In March, Veritas Genetics announced pre-orders for whole genome sequencing, plus interpretation and counselling, for US$999.
Another genetics-based start-up, Human Longevity Inc (HLI), believes abundant, relatively affordable sequencing and collecting other biological data will revolutionise healthcare delivery. Founded by Venter, stem cell specialist Robert Hariri and entrepreneur Peter Diamandis, it claims to have sequenced more human genomes than the rest of the world combined, with 20,000 last year, a goal of reaching 100,000 this year and over a million by 2020.
HLI offers to “fully digitise” a patient’s body – including genotypic and phenotypic data collection, and MRI, brain vascular system scans – under its US$25,000 Health Nucleus service. Large-scale machine learning is applied to genomes and phenotypic data, following the efforts at what Venter has called “digitising biology”.
The claim is that artificial intelligence (AI) can predict maladies before they emerge, with “many” successes in saving lives seen in the first year alone. The company’s business includes an FDA-approved stem cell therapy line and individualised medicines. The slogan “make 100 the new 60” is sometimes mentioned in interviews with founders. Their optimism is not isolated. Venture capitalist Peter Thiel admits he takes human growth hormone to maintain muscle mass, confident the heightened risk of cancer will be dealt with completely by a cancer cure, and plans to live to 120.
“We understand what the surgeon needs and we embed that in an algorithm so it’s full automated.”
Bill Maris, CEO of GV (formerly Google Ventures), provocatively said last year that he thinks it’s possible to live to 500. An anit-ageing crusader, biological gerontologist Dr Aubrey de Grey, co-founder and chief science officer of Strategies for Engineered Negligible Senescence (SENS, whose backers include Thiel), has claimed that people alive today might live to 1000.
Longevity expectations are constantly being updated. Consider that, in 1928, American demographer Louis Dublin put the upper limit of the average human lifespan at 64.8. How long a life might possibly last is a complex topic and there’s “some debate”, says Professor of Actuarial Studies at UNSW Michael Sherris.
He says there have been studies examining how long a life could be extended if certain types of mortality, such as cancer, were eliminated, points out Sherris.
“However, humans will still die of something else,” he adds. “The reality is that the oldest person lived to 122.”
Will we see a 1000-year-old human? It isn’t known. What is clear, though, is that efforts to extend health and improve lives have gotten increasingly sophisticated.
The definition of bioengineering has also grown and changed over the years. Now concerning fields including biomaterials, bioinformatics and computational biology, it has expanded with the ability to apply engineering principles at the cellular and molecular level.
Editing out problems to reverse ageing
What if, further than reading and comprehending the code life is written in, it could also be rewritten as desired? A technique enabling this with better productivity and accuracy than any before it, has gotten many excited about this possibility.
“In terms of speed, it’s probably 10 times as quick as the old technology and is five to 10 times as cheap,” says Professor Robert Brink, Chief Scientist at the Garvan Institute of Medical Research’s MEGA Genome Engineering Facility.
The facility uses the CRISPR/Cas9 process to make genetically-engineered mice for academic and research institute clients. Like many labs, Brink’s facility has embraced CRISPR/Cas9, which has made editing plant and animal DNA so accessible even amateurs are dabbling.
First described in a June 2012 paper in Science, CRISPR/Cas9 is an adaptation of bacteria’s defences against viruses. Using a guide RNA matching a target’s DNA, the Cas9 in the title is an endonuclease that makes a precise cut at the site matching the RNA guide. Used against a virus, the cut degrades and kills it. The triumphant bacteria cell then keeps a piece of viral DNA for later use and identification (described sometimes as like an immunisation card). This is assimilated at a locus in a chromosome known as CRISPR (short for clustered regularly spaced short palindromic repeats).
In DNA more complicated than a virus’s, the cut DNA is able to repair itself, and incorporates specific bits of the new material into its sequence before joining the cut back up. Though ‘off-target’ gene edits are an issue being addressed, the technique has grabbed lots of attention. Some claim it could earn a Nobel prize this year. There is hope it can be used to eventually address gene disorders, such as Beta thalassemias and Huntington’s disease.
“Probably the obvious ones are gene therapy, for humans, and agricultural applications in plants and animals,” says Dr George Church of Harvard Medical School.
Among numerous appointments, Church is Professor of Genetics at Harvard Medical School and founding core faculty member at the Wyss Institute for Biologically Inspired Engineering. Last year, a team led by Dr Church used CRISPR to remove one of the major barriers to pig-human organ transplants – retroviral DNA – in pig embryos.
You can have what are called, ‘universal donors’. That’s being used, for example, in making cells that fight cancer.
“We’re now at the point where it used to be that you would have to have a perfect match between donor and recipient of human cells, but that was because you couldn’t engineer either one of them genetically,” he says. “You can engineer the donor so that it doesn’t cause an immune reaction. Now, you can have what are called, ‘universal donors’. That’s being used, for example, in making T cells that fight cancer – what some of us call CAR-T cells. You can use CRISPR to engineer them so that they’re not only effective against your cancer, but they don’t cause immune complications.”
Uncertainty exists in a number of areas regarding CRISPR (including patent disputes, as well as ethical concerns). However, there is no doubt it has promise.
“I think it will eventually have a great impact on medicine,” believes Brink. “It’s come so far, so quickly already that it’s almost hard to predict… Being able to do things and also being able to ensure everyone it’s safe is another thing, but that will happen.”
And as far as acceptance by the general public? Everything that works to overcome nature seems, well, unnatural, at least at first. Then it’s easier to accept once the benefits of are apparent. Church – who believes we could reverse ageing in five or six years – is hopeful about the future. He also feels the world needs people leery about progress, and who might even throw up a “playing God” argument or two.
“I mean it’s good to have people who don’t drive cars and don’t wear clothes and things like that, [and] it’s good to have people who are anti-technology because they give us an alternative way of thinking about things,” he says.
“[Genetic modification] is now broadly accepted in the sense that in many countries people eat genetically-modified foods and almost all countries, they use genetically-modified bacteria to make drugs like Insulin. I think there are very few people who would refuse to take Insulin just because it’s made in bacteria.”
A complete mindshift
Extended, healthier lives are all well and good. However, humans are constrained by the upper limits of what our cells are capable of, believes Dr Randal Koene.
For that and other reasons, the Dutch neuroscientist and founder of Carbon Copies is advancing the goal of Substrate Independent Minds (SIM). The most conservative form (relatively speaking) of SIM is Whole Brain Emulation, a reverse-engineering of our grey matter.
“In system identification, you pick something as your black box, a piece of the puzzle small enough to describe by using the information you can glean about signals going in and signals going out,” he explains, adding that the approach is that of mainstream neuroscience. “The system identification approach is used in neuroscience explicitly both in brain-machine interfaces, and in the work on prostheses.”
No brain much more complicated than a roundworm’s has been emulated yet. Its 302 neurons are a fraction of the human brain’s roughly 100 billion.
Koene believes that a drosophila fly, with a connectome of 100,000 or so neurons, could be emulated within the next decade. He is reluctant to predict when this might be achieved for people.