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DNA-Based Approaches Offer Improvements in Crop Science

While debate around DNA engineering in crops continues, it is worth remembering that one of the greatest accomplishments of the 20th century came from a plant biologist and geneticist who would go on to win the Nobel Prize and be called “The Man Who Saved a Billion Lives.”

That man was Norman Borlaug, a plant scientist who used the cutting-edge genetic techniques of the 1940s and 1950s to develop several varieties of high-yielding, semi-dwarf wheat that were resistant to disease. At the time, these crops provided a path forward for Mexico, India, and Pakistan — countries that were importing wheat or whose populations were facing the very real scenario of starvation. Wheat production more than doubled as these countries converted to the Borlaug wheat, which was later introduced throughout Asia and Africa. In 1970, Borlaug was honored with the Nobel Peace Prize in recognition of the agricultural wonders he had worked.

As the world population booms, it is critical that each arable acre yield more and more food than ever before. By some estimates, just 15 crops represent 90 percent of the world’s food supply — putting remarkable pressure on every one of those crops to produce reliable yields with every planting.

Agricultural biologists have a tremendous imperative to develop higher-yielding, nutrient-rich crops that resist pests, drought, and disease. In Borlaug’s day, this entailed a long and complex process of backcrossing, shuttle breeding, and using multiline varieties to create plant strains with favored traits, such as shorter stalks or resistance to rust. Today, new DNA-based technologies have been brought to bear on this important work. Scientists can more precisely target favored traits by studying the genetics of crop plants and altering strains to carry a particular gene or variant of interest. In other studies, agbio companies can take seed samples from farmers, perform genetic assessments of them, and report back to the farmer which seeds are most likely to succeed in particular environmental conditions and for certain crop goals.

The introduction of biotechnology to agricultural studies will be remembered as a major revolution in understanding and developing crops best suited to feeding the world’s people and animals. We are witnessing the earliest stages of it, but recent advances in agbio show just how promising these improved crop science approaches will be. As we look ahead, new technology innovations will enable progress at an even faster rate than we see today.

Crop Science and DNA

The earliest days of using DNA-targeting technologies allowed crop scientists to make major improvements with key plant traits, from production to flavor and more. According to Paul Schickler, president of DuPont Pioneer, the average corn yield in the United States was about 30 bushels per acre in the 1920s. With the introduction of hybrid corn and other improvements, today that number is 160 bushels per acre. In a recent interview with Bloomberg, Schickler said, “I hesitate to think what we’d be faced with today, around the world and in the United States, if we were using practices and seeds from one hundred or two hundred years ago.” 

Just a couple of decades after Borlaug’s backcrossing, scientists determined how to use gene splicing and other DNA-based approaches to accomplish the same breeding goals with better accuracy, reliability, and predictability. Genetic modification allowed scientists to knock out or knock in genes, introduce point mutations, or incorporate transgenic DNA. By the mid ’80s, tobacco became the first crop modified with these techniques; it was engineered to resist herbicides. By 2009, 15 countries including the US, Brazil, and Argentina were considered mega-producers of these biotech crops, growing at least 50,000 hectares. One of the most significant strides in the introduction of these crops was that they facilitated no-tilling farming; this was enabled by herbicide-tolerant plants and greatly reduced soil erosion in regions that struggle to maintain arable land.

A specific study into the effects of such genetically modified crops (Graham Brookes and Peter Barfoot, “The income and production effects of biotech crops globally 1996–2010.” GM Crops and Food, Oct/Nov/Dec 2012) found that production of four common crops — soybeans, corn, cotton, and canola — increased by more than 275 million tons worldwide due to “positive yield effects of biotech crops.” An earlier study from the same authors reported that biotechnology-modified crops allowed farmers to reduce pesticide spraying by almost 9%, or more than 430,000 tons of herbicide and insecticide.

New Genomic Approaches

As rudimentary genetic approaches gave way to more complete genomic views of crops, scientists have continued to hone their ability to develop and identify plants that have promising traits for particular environments or goals. Some of today’s most cutting-edge innovations in crop science are coming from next-generation DNA sequencing, transcriptome profiling, and small RNA studies.

New DNA sequencing technologies are providing a more comprehensive view of complex plant genomes than has ever been possible; many scientists have embraced a hybrid approach that merges short sequence reads with long-read data to generate high-quality assemblies of rice, wheat, and other important crop plants. These approaches also reveal crucial information about particular traits. At a recent agbio conference, scientists from the Yunnan Academy of Agricultural Sciences and Kunming Institute of Zoology in China presented data showing that deep sequencing could be used to find SNPs associated with traits bred into elite crop strains — an advanced genomic analysis that helps scientists understand the genetic basis for high-functioning crops created through backcrossing, for example. Additional analysis can identify which traits are best suited for certain growing conditions and allow for the rapid development of new elite strains for specific regions. In other studies, comparisons of sequence data between disease-resistant and wild-type strains have detected important differences in gene copy number or methylation status.

Sequencing tools can also be used to study RNA for transcriptome analysis. RNA-seq, as this approach is known, is frequently used to compare two varieties of the same plant to determine which genes are actively involved at certain times. Recent studies have used this method to reveal more information about the drought response in sugarcane and generate a pathway analysis of wheat genes associated with the onset of wheat leaf rust. One project recently reported by scientists from the University of Illinois-Urbana detailed the use of RNA-seq to profile gene expression in soybean seeds during different stages of development, from shortly after fertilization to maturity. The effort found considerable activity among genes involved in storage proteins and also identified hundreds of transcription factors that were turned on in various developmental stages.

Small RNAs have proven to be another valuable way to look at gene expression. RNA interference is useful in crop science — fittingly, since the biological mechanism was first identified in petunias — for silencing certain genes to monitor the downstream effect. Scientists around the world are using this technique, often to assess the relevant genes during interactions between plants and pathogens. As those genes are identified, scientists will have another avenue to help prevent the spread of disease among crops.

The Latest Innovation

As plant genomics becomes increasingly essential for the design and production of disease-resistant, high-yielding crops, agbio researchers are being constrained by their ability to test and tweak genes in plants. The current standards for building DNA lack scalability and need improvement in accuracy, length, and turnaround time. The accepted method of stitching together relatively short oligos to produce longer DNA constructs is tedious, manual, and error-prone.

A new approach to gene synthesis has been developed by academic scientists and stands to alleviate these challenges. Based on work from George Church at Harvard, Joseph Jacobson at MIT, and Drew Endy at Stanford, this new technology uses synthetic biology as a novel way to generate DNA constructs. The approach has been commercialized by Gen9, a startup based in Cambridge, Mass., which has built the first gene synthesis fabrication platform based on silicon chips and today offers lower-cost, longer, more accurate constructs. The technique uses highly multiplexed gene synthesis and a novel error-correction pipeline to produce synthetic DNA at far greater scale than is possible with other tools; capacity can be added on an exponential scale.

Known as the BioFab platform, the technology can generate tens of thousands of DNA constructs per year. In 2013, Gen9 anticipates that its next-generation gene synthesis platform will have the capacity to produce as much synthetic DNA in a single lab as can be produced by the rest of the world. This improvement will be revolutionary to the agbio research community, which will be able to use these longer, higher-accuracy, lower-cost gene constructs to test far more genes — indeed, whole pathways at a time — across many more plants than can be done with currently accepted practices. For the first time, gene synthesis will be a cost-effective option for scientists working to improve crops.

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Editor's note: By Martin Goldberg, PhD

Martin Goldberg, PhD is the Chief Operating Officer at Gen9, a developer of scalable technologies for synthesizing and assembling DNA.

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