In a changing climate, corn growers need to be ready for anything, including new and shifting disease dynamics. Because it’s impossible to predict which damaging disease will pop up in a given year, corn with resistance to multiple diseases would be a huge win for growers. Now, University of Illinois Urbana-Champaign researchers are moving the industry closer to that goal. 

Goss’s wilt, a bacterial disease, and fungal diseases gray leaf spot, northern corn leaf blight, and southern corn leaf blight are important to growers across the Midwestern US and, in some cases, globally. The study, published in G3 Genes|Genomes|Genetics, reveals genomic regions associated with resistance to all four diseases.

“We not only found regions of the genome conferring resistance to each disease, but also identified a handful of experimental corn lines that were resistant to all of them. These findings should help the industry develop materials with resistance to multiple diseases at once,” said Tiffany Jamann, senior author of the new study and associate professor in the Department of Crop Sciences, part of the College of Agricultural, Consumer and Environmental Sciences at the University of Illinois, Urbana-Champaign.

The team made several strategic crosses between disease-resistant and susceptible corn lines that let them map resistance traits to specific locations in the genome. For now, those regions are fairly large, comprising hundreds of individual genes. If there are specific genes with outsized effects, they haven’t been identified yet. 

Still, identifying important regions is helpful, as disease resistance rarely comes down to a single gene. In fact, the additive or quantitative power of multiple genes working together can mean more durable resistance. There’s a backup if a pathogen finds a way around a given resistance mechanism. Interestingly, this durability may even work against different groups of pathogens. 

“We found 19 regions associated with resistance to the bacterial disease Goss’s wilt. Several of those regions are also involved with resistance to fungal pathogens,” Jamann said. “Thus, it is possible to breed for resistance to several diseases at one time using the same genetic regions.”

Fungi and bacteria are very different biologically, but both have to find ways to get into the plant, travel throughout, and reproduce. Jamann says it’s possible that resistance genes trigger changes in the plant’s vasculature to make it harder for both kinds of pathogens to move around, but she still can’t say exactly how the genes help plants protect themselves. She’s working on it, though, thanks to a 2022 grant from the National Science Foundation.  

Although the team identified three corn lines with resistance to all four diseases, it will be a while before growers can purchase seed for multiple-resistant corn as a result of this work. First, Jamann’s team will fine-map the regions highlighted in this study to find any major-effect genes, then pass that information off to breeders who can develop hardy new hybrids. Still, Jamann says, multiple resistance is on its way.

This post has been republished with permission of the author.

Ever feel like you’re working for peanuts? When it comes to world food sustainability, geneticists argue, peanuts are the whole point.

Research published by Conde et al. in the latest issue of G3: Genes|Genomes|Genetics underscores the importance of peanut farming in the pursuit of global food security–and describes a new tool to make the legume even more resilient to climate change.  

The study churns around Arachis hypogaea L.—better known as peanut or groundnut—which is commonly grown on small farms in developing countries for food, fodder, and profit. Over time, peanuts lost some of their resiliency as today’s allotetraploid plant was hybridized, domesticated, and adapted to meet consumers’ demands. In favor of higher yield and bigger, tastier nuts for consumers, breeders lost some of the genetic diversity that allowed the plant to fight certain diseases or withstand drought. Now, restoring genetic diversity is the key to developing better peanut breeding, and by extension, striving for global food security.

It’s a tough nut to crack, but that’s where core collections come in. These collections are groups of crop genotypes that reveal valuable molecular information, helping breeders map traits of interest. Core collections have enhanced the production of other crops like rice and wheat, and while several have been created for peanuts, they were developed before the advent of sophisticated genotyping technologies.

As groundnut breeders from various countries in Western Africa joined together with colleagues in Eastern and Southern Africa, the Groundnut Improvement Network for Africa (GINA) was launched. This collaborative group of ten breeding programs compiled more than 1,000 peanut varieties from nine countries—breeders were asked to nominate their preferred peanut lines—and analyzed them to create a core collection. In this new study, researchers explore the genetic diversity in those lines.

Using expected heterozygosity (H_e), a common measure for genetic variation within populations, the authors clustered groundnuts into three market types: Spanish, Valencia, and Virginia, and categorized them into one of two subspecies–most were fastigiata, while the rest were hypogaea.

When they dug deeper to analyze the genetic structure of the collection, the authors found that most of the breeding programs were rooted in an admixed genetic heritage, meaning they were a mix of multiple market types. This was especially true of the Valencia groundnuts. The authors also found that several lines of nuts had been nominated by more than one breeding program, suggesting past germplasm exchange. Some lines went by the same common name in different countries but were genetically different, demonstrating how difficult it can be to accurately record and manage germplasm.

The researchers developed a core collection of 300 accessions based on traits (breeder choices) and diversity (genetic distance-based sampling). While geneticists use this information to map favorable crop traits like resistance to disease, several peanut lines have already made their way into advanced release pipelines, spreading the agronomic and nutritional assets of this core collection to farmers and consumers.

The power of the collection lies in its collective genetic variability, a unique compilation of the many small but diverse collections throughout Africa. In a nutshell, this much-needed resource will help mobilize peanut diversity to make the plant—and the farmers that grow it—more resilient in the face of future challenges.

Aspergillus fumigatus isolated from clinical settings is resistant to agricultural fungicides.

Infections have long been a deadly problem for hospital patients. Though modern medicine has an impressive array of antimicrobial drugs at its disposal, pathogens continue to evolve resistance, creating ever more dangerous infections as the microbial “arms race” escalates.

Overprescribing of antibiotics is one source of resistance, but there could be another culprit further afield. In a new publication in G3: Genes|Genomes|Genetics, fungal biologists Michelle Momany and Marin Brewer report their finding that some strains of a pathogenic fungus apparently acquired antifungal resistance in an agricultural setting rather than a clinical one. Genetic analysis revealed that strains of the fungus Aspergillus fumigatus that were resistant to antifungals used in people had also developed resistance to fungicides used only on plants.

Fungal infections endanger both plants and people

Momany and Brewer are part of the Fungal Biology Group at the University of Georgia, one of the largest fungal biology research groups in the world. Fungal diseases are a major problem both clinically and in agriculture, but doctors generally use different compounds to treat people than farmers use to treat crops. A class of antifungals known as azoles, however, is used in both people and plants. Many different azoles are currently available, and though they are considered “moderate” in terms of the risk of fungi developing resistance, azole-resistant strains of the fungus Aspergillus fumigatus have begun turning up more frequently in hospitals.

Unlike drug-resistant bacteria, which can spread from person to person, A. fumigatus is always picked up environmentally. There’s no documented case of anyone getting sick by breathing in Aspergillus exhaled by an infected patient, says Momany. Because of this, fungal researchers suspected A. fumigatus was evolving azole resistance in the field, rather than in patients. Still, there was no way to know for sure that it wasn’t caused by hospital drugs.

From “Big Chicken” to Big Tulip

“The idea came to me when I was reading the book Big Chicken by Maryn McKenna,” says Brewer. In the book, scientists showed that antibiotic-resistant bacteria had moved from chickens to humans – not the other way around – by showing that bacteria isolated from people contained genetic evidence of resistance to compounds used only in chickens. Brewer decided to apply that same logic to Aspergillus. “I thought it would be interesting to look for the signatures for resistance to fungicides only used in agricultural environments,” she says.

The researchers analyzed 700 different isolates of A. fumigatus collected from compost heaps, soil samples, and plant debris from 56 sites around Georgia and Florida. They sequenced and analyzed the genomes of 135 of these isolates. Most of the sites had a history of azole fungicide use, but two were organic sites with no fungicide use for 10 years. They also analyzed publicly available genome data of A. fumigatus samples from the US, the UK, the Netherlands, and India that were resistant to multiple azole compounds. 

They found that A. fumigatus in the environment that carried resistance to azole compounds had often developed resistance to two other classes of fungicides used only in agriculture, benzimidazoles (MBC) and quinone outside inhibitors (QoI). Even more tellingly, A. fumigatus samples collected from patients carried the genetic markers indicating resistance to MBC and QoI.

“Those signatures showed that they were exposed to fungicides in an agricultural environment, and we’re finding them in strains from patients in hospital environments,” says Brewer.

The first hint that agricultural fungicides might be a problem in hospitals came from the Netherlands, the world’s major supplier of tulips and other ornamental flowers. “It turns out a tulip bulb is a wonderful place for fungi to grow,” Momany says. “Nobody wants decorative flowers with mold spots on them. To prepare these for shipping, they’re treated with azoles.” Discarded plant matter from these industrial tulip farms, she says, can spread azoles into the surrounding environment. Strikingly, Momany points out, A. fumigatus isn’t even dangerous to plants. It’s not the intended target of agricultural azole use, but because it’s so widespread, it gets exposed incidentally. “Once those azoles are in the environment, then the A. fumigatus that’s there develops its own resistance,” she says.

People are likely to encounter azole-resistant A. fumigatus in compost or in flower beds. “Compost is definitely a hot spot for Aspergillus that’s azole resistant,” says Brewer. “People who are immunocompromised should be very careful around compost, flower beds, or dusty areas where there can be a lot of fungi.”

This study is one of the first to characterize a fungal pathogen that has picked up antifungal resistance in an agricultural setting and carried that resistance into the clinic. “There could be a lot of others, and people just haven’t looked,” Brewer says.

CITATION:

Evidence for the agricultural origin of resistance to multiple antimicrobials in Aspergillus fumigatus, a fungal pathogen of humans

S. Earl Kang, Leilani G. Sumabat, Tina Melie, Brandon Mangum, Michelle Momany, and Marin T. Brewer

G3: GENES|GENOMES|GENETICS February 2022, jkab427

https://doi.org/10.1093/g3journal/jkab427

Researchers identified dozens of quantitative trait loci controlling important traits in Cannabis sativa.

In 2014, United States federal law changed to allow scientific research on Cannabis sativa in states with regulated hemp programs. This legal shift opened the door to research that had previously been slow and difficult due to regulatory hurdles and funding challenges.

A new study published in GENETICS capitalized on this new opportunity and identified 69 quantitative trait loci (QTLs) that are responsible for variation in key agronomic and biochemical traits in C. sativa. This research is a step towards understanding the genetic control of complex traits in hemp and will inform future investigations into the overall evolution and function of complex traits across multiple species.

Hemp is grown for a wide range of commercial uses, including in building materials, textiles, and composite plastics, food and drink, animal feed, and pharmaceutical cannabinoid products, says study leader John McKay of Colorado State University. “It’s important to understand the genes controlling this plant as a crop, and it’s also interesting from a fundamental evolutionary standpoint.”

Identifying QTLs in a non-model species

“Scientists have previously made progress in identifying the genetic basis of complex traits in model and crop species—our team wanted to ask those questions in C. sativa because it’s an understudied species,” says McKay.

Today’s genome sequencing and assembly technologies are largely species-agnostic. As a result, scientists can now take bioinformatic and statistical genetic tools that were initially developed and tested in fruit flies and Arabidopsis and increasingly apply them to non-model species.

McKay and his team developed an F₂ hemp population by crossing two phenotypically distinct varieties—a tall, late-flowering cultivar bred for fiber production and a shorter, early maturing hemp that was bred for both fiber and grain crops. They then used whole genome sequencing to map QTLs associated with traits of interest, such as grain yield and stem biomass, along with 17 biochemical traits. These included levels of cannabidiol and terpenes, which have medical uses, and THC, which is the psychoactive component of marijuana. THC is strictly regulated in the US, and THC levels in industrial hemp must be below 0.3% to remain legal crops.

Most QTLs they identified clustered into one of four genomic regions, suggesting that much of the difference between the two varieties is due to a small number of genes that have large pleiotropic effects. Two candidate genes emerged that may underlie some of these clusters: the homolog of an Arabidopsis transcription factor gene called TINY may be associated with a cluster of agronomic traits, and the gene for olivetol synthase appears to underlie variation in a cluster of biochemical traits, consistent with the enzyme’s role in cannabinoid synthesis. The researchers functionally validated the olivetol synthase candidate by expressing the two hemp alleles in yeast. They found that the allele from the low-cannabinoid cultivar produced less olivetol in the yeast expression system, supporting the hypothesis that allelic variation at this gene plays a role in the observed phenotypic variation.

The researchers also observed epistatic interactions between some of the QTL clusters, further complicating attempts to elucidate any one trait’s exact genetic underpinnings.

“This study definitely adds to the broader conversation about complex traits,” says McKay. “For example, everyone agrees epistasis exists, but breeders and geneticists like to argue about whether it’s important to include in prediction models. Documenting additional cases like this in which epistasis contributes to variation adds to our understanding of the basis of complex traits.”

Traits are complicated but still predictable

The results of this latest study contradict a paper from 2003 that concluded that variation in cannabinoid production is controlled by a single genetic locus. The team from Colorado State University identified at least four loci controlling variation in these chemotypes.

“The field of genetics has always been a friendly place to hypothesize that something—anything—is polygenic,” laughs McKay. “Finding multiple loci controlling a single biochemical trait wasn’t surprising to me, because the abundance of any molecule can be influenced not only by the pathway that makes that molecule but also the ones that influence the cells and machinery that contribute to the process.”

However, despite overturning assumptions of one-to-one genotype-phenotype interactions, McKay emphasizes that he still views the hemp traits in the study as predictable. Future grants would allow research groups like his to dive deeper into the adaptive value of cannabinoids in hemp plants and create more precise genetic manipulations of key traits of interest. Researchers are eager to see policy informed by scientific understanding of the factors that predictably affect cannabinoid content and other traits in hemp crops.

CITATION:
Quantitative Trait Loci Controlling Agronomic and Biochemical Traits in Cannabis sativa
Patrick Woods, Brian J. Campbell, Timothy J. Nicodemus, Edgar B. Cahoon, Jack L. Mullen, and John K. McKay
GENETICS 2021; iyab099
https://doi.org/10.1093/genetics/iyab099

Geneticists dig up the dirt on 300 years of succulence.

When Steve Knapp started his new job at the University of California, Davis, he plunged into a forensic mystery that would take years to unravel. He wasn’t hunting a criminal or identifying a missing person, but the challenge before him was just as formidable: reconstructing the genetic identity of more than one thousand strawberry plants owned by the university. In the end, the strawberry genealogy would expand to include over 8,000 individuals around the world.

Knapp is director of the Strawberry Breeding Program at UC Davis. The humble strawberry, that ubiquitous staple of summer picnics, represents big business for the University of California. Strawberries bred at UC Davis account for around half of California’s $2.6 billion annual crop. “In the entire UC system, for many years, it was the top royalty generator,” said Knapp. While pharmaceuticals have now taken the lead, licensing fees from the berries still bring in more than $7 million a year.

UC Davis hired Knapp in 2015 to restore confidence in their strawberry breeding program after the previous director left to start his own private breeding company. Fearing the program would be shuttered, the California Strawberry Commission (CSC) sued the school. Knapp was brought on board as part of the university’s settlement with the CSC, reinforcing the program’s commitment to continue producing new strawberry varieties.

Knapp faced a massive challenge. To successfully breed the plants, he had to know what the program’s historic collection contained, but some 95% of the pedigree records were missing. With around 1,500 specimens and sparse records, he and his team would need to draw on a combination of molecular genetic techniques and old-fashioned genealogical detective work to document the collection.

Now published in G3: Genes|Genomes|Genetics, this huge curation project also explored the tangled roots of today’s strawberries. Modern varieties were first created in 18^th century France from spontaneous crosses between the Chilean strawberry and another New World import, the Virginian strawberry. After the mysterious parentage of these cultivars was uncovered by a teenage botanist working in the palace gardens of Versailles, horticulturalists developed the fruit into the large berries recognizable to shoppers today.

But this long-told origin story glosses over the true complexity of the modern strawberry’s ancestry. Over the years, breeders intensively crossed, back-crossed, and selected countless varieties from across the world, repeatedly introducing various wild species into the mix. The genetic twists and turns of strawberry domestication are still not fully understood.

To map the relationships between specimens in the university collection, the team used high-density single nucleotide polymorphism (SNP) genotype analysis. They genotyped every individual plant in the collection and applied statistical analyses to establish parent-offspring relationships. The pedigrees that they generated—replete with long-lived individuals, overlapping generations, and extensive hybridization—became too large and complex for conventional pedigree visualization software, so the researchers turned to tools for social network analysis to identify patterns and relationships between the plants. This method enabled them to visualize the diversity of individual plants that have “founded” domesticated populations over the 300-year history of strawberry cultivation.

To delve beyond the Davis collection, Knapp posed a challenge to the members of his lab. “I said, it would be really cool to connect this UC material to the founders that created it,” he said. “Where did that material come from?”

Graduate student Dominique Pincot sank her teeth into the project. She followed the paper trail to the University of Utah, where she found a set of notebooks containing pedigrees recorded by Royce Bringhurst, “Mr. Strawberry,” who headed the UC Davis program from 1952 to 1989.

Next, the team tracked down pre-WWII pedigrees from the UC collection that had made their way to Driscoll Strawberry Associates, the commercial berry seller. “We literally had these three-ring binders full of crusty old notes of pedigrees that gave us a pretty good reconstruction all the way back to the early Berkeley days,” Knapp said.

Each new thread led to another set of records, and Pincot continued tracing various lineages back through North American and European records and catalogs. The project amassed over 800 sources of data documenting the genealogy of today’s strawberry varieties, and the pedigree encompassed 8,851 individual plants.

“We eventually translated this from this massive legal battle into a labor of love,” Knapp said. “It became extremely fun for us.”

Besides the practical benefit to the UC Davis breeding program, the strawberry genealogy project provides broader scientific benefits. Understanding how modern strawberry genetics relates to earlier varieties is informative because agricultural cultivation often reduces genetic variation within a species. Ultimately a lack of diversity from too much inbreeding can harm the health of the species as well as limiting the options for introducing new traits. Knapp’s analysis revealed that although more than 80% of ancestor strawberries are now extinct, the modern strawberries have retained a great deal of genetic diversity from those ancestors.

Additionally, the project shed light on the breeding speed of the strawberry, or the number of years between generations. “We showed that the breeding cycle was fairly long,” said Knapp. “We made the argument that genetic gains can be increased by speeding it up.” The breeding cycle has decreased over the last 200 years from nearly 17 years per generation down to about six. Faster breeding times would enable the introduction of more genetic variation.

Having this genealogical information to hand has already enabled new kinds of strawberry genomic analysis and tool development. It also advances predictive breeding, a method that uses genetic information to forecast which offspring will have desired traits. “This project was meant to tell us, how did we get here and where have we been, and how can we use this information to predict the future,” said Knapp.

CITATION

Social network analysis of the genealogy of strawberry: retracing the wild roots of heirloom and modern cultivars

Dominique D A Pincot, Mirko Ledda, Mitchell J Feldmann, Michael A Hardigan, Thomas J Poorten, Daniel E Runcie, Christopher Heffelfinger, Stephen L Dellaporta, Glenn S Cole, Steven J Knapp

G3 Genes|Genomes|Genetics, Volume 11, Issue 3, March 2021, jkab015, https://doi.org/10.1093/g3journal/jkab015

Newly uncovered newspaper articles shed light on Mendel’s motivations.

Gregor Mendel is considered by many to be the father of genetics. Yet, because his work was not fully appreciated in its time, little is known about Mendel himself. Primary sources, such as letters he wrote, are rare; only a few dozen pieces of his correspondence remain—in contrast, over 15,000 of Charles Darwin’s letters survive. Without adequate source material to settle the subject, Mendel’s intentions in studying plants have long been the subject of debate. In GENETICS, van Dijk et al. report on two newly unearthed newspaper articles that provide some insight into Mendel’s motivations.

Standard interpretations of Mendel’s intentions agree that he was trying to figure out the rules of inheritance. However, others have argued that this explanation is biased by a modern perspective that knows his eventual findings, rather than truly considering what prompted him to begin his experiments in the first place. Some versions of this “revisionist” view hold that Mendel was primarily concerned with whether new species could be produced from hybridization. Although strong feelings exist in each camp, with so few primary sources, Mendel’s motives have remained primarily a matter of speculation.

Van Dijk and his colleagues found two previously overlooked articles in a database of scanned newspapers. The first, published on July 26, 1861, is a glowing account of Mendel performing “very instructive experiments, which are aimed at improving the vegetable and flower varieties cultivated in our region.” It discusses the “truly surprising” results of his work with artificial fertilization, including the production of “towering vegetable bushes” bearing plentiful (and tasty) fruit.

The second article was a rather pointed response to the first, published just four days later: “Without wanting to offend Professor Mendl [sic], for we honor every endeavor to approach truth in a practical manner, we must make [the newspaper’s] readers aware of the true value of the matter, which the reporter has somewhat exaggerated.”

The authors of the response then detail some of the ways the original newspaper report distorted the practical implications of Mendel’s work. For example: “Concerning the bastardization of beans, peas or fisols and cucurbits; the seed catalogs from France, England and Germany list so many varieties of excellent quality that it is hardly noteworthy to mention the economic importance of these very small scale experiments.” In other words, it might be interesting science, but the immediate implications were considered minimal at the time.

In some ways, these two articles are reminiscent of a phenomenon that continues to occur in science communication today: the ramifications of new science can be over-exaggerated when reported to a broad audience. Notably, however, the second article suggests that Mendel was actively seeking to answer a scientific question. Combining the new evidence with scholarship on Mendel’s scientific and horticultural influences, the authors make the case that Mendel’s motivations evolved: his practical interests in breeding sowed the seeds of a pursuit of pure science.

CITATION:

How Mendel’s Interest in Inheritance Grew out of Plant Improvement

Peter J. van Dijk, Franz J. Weissing, T. H. Noel Ellis

GENETICS October 1, 2018 210: 347-355; https://doi.org/10.1534/genetics.118.300916

http://www.genetics.org/content/210/2/347

Expression analysis provides clues about what makes some peanut strains more susceptible to fungal toxin contamination.

In 1960, 100,000 turkeys across hundreds of English poultry farms died from aflatoxin contamination in the peanut meal in their feed. Aflatoxin is a potent carcinogen produced by fungi of the genus Aspergillus, which can grow on peanuts. Although the peanut butter in your supermarket is tested for aflatoxin before it reaches you, fungal toxin contamination remains a major problem for peanut producers. Some peanut strains are more likely to become contaminated than others, but the reasons for this difference aren’t clear.

In a report in GENETICS, Korani et al. examined the transcriptomes of peanuts and fungi to gain a better understanding of what makes some peanuts resistant to contamination with aflatoxin. The authors chose two strains of peanut—one that was resistant to aflatoxin contamination and one that was susceptible. They infected some seeds with the aflatoxin-producing fungus Aspergillus flavus, leaving some seeds uninfected as controls. They used RNA-seq to examine differential gene expression in both the peanuts and the fungus.

By comparing gene expression between uninfected and infected seeds and between resistant and susceptible strains, the authors were able to identify consequential pathways. They found that resistant plants had higher expression of genes involved in the synthesis of jasmonates, which are plant hormones known to be involved in plants’ response to biotic stresses, such as insects. This suggests that jasmonates might inhibit fungal production of aflatoxin.

The authors also examined the transcriptome of A. flavus grown on resistant or susceptible peanut seeds. Interestingly, they found significant differences in the expression of a number of metabolic genes, particularly those involved in carbohydrate processing. These results suggest that different peanut strains may alter the metabolism of fungi growing on them, leading to decreased aflatoxin production.

This study provides clues as to potential mechanisms of aflatoxin contamination-resistance in peanuts. The authors note that the study was not designed to identify individual genes important in resistance phenotypes; they analyzed whole pathways instead. Further studies will be needed to demonstrate causality, but a better understanding of these resistance mechanisms will help farmers ensure that our beloved peanut butter remains safe to consume.

CITATION:

Insight into Genes Regulating Post-harvest Aflatoxin Contamination of Tetraploid Peanut from Transcriptional Profiling

Walid Korani, Ye Chu, C. Corley Holbrook, Peggy Ozias-Akins

GENETICS May 1, 2018 vol. 209 no. 1 143-156; DOI: 10.1534/genetics.118.300478

Archaeologists have long known how to extract millennia-old stories from a single tooth buried in an ancient ruin—and now geneticists have the tools to join them. Advances made in the last several years have enabled researchers to sequence tiny amounts of DNA preserved in very old specimens, such as the material inside a tooth from the Stone Age. But this ancient DNA (aDNA) is often severely degraded, limiting its use. In GENETICS, Joshua Schraiber describes a new statistical approach to getting the most from these old samples and reports how he used the method to uncover secrets about the relationships between ancient humans and modern ones.

A major obstacle to understanding humans’ recent evolutionary history has been the inability to infer much about it using genetic data from people living today. If restricted to data from modern people, we would be locked out of information of great scientific and cultural relevance. The genetic relationships between ancient and modern populations can provide clues about migrations that occurred thousands or tens of thousands of years ago and help us better understand our histories. For example, researchers recently found that many people living in South America today are in part descended from an ancient North American group called the Clovis people.

Solving these kinds of puzzles is where aDNA shines—if you know how to use it. Schraiber found that the best way to determine genetic relationships among modern and ancient populations using degraded samples of aDNA is to sequence multiple ancient samples at low coverage rather than fewer samples at high coverage. After applying his new method to existing genetic data from 230 West Eurasian people who lived 8500–2300 years ago, Schraiber discovered that none of them came from populations that are direct ancestors of any modern European populations tested.

Schraiber’s analysis also suggests many ancient European people separated into small populations with little gene flow among them, and that most of these local groups died out, leaving a limited genetic legacy in modern European people. His results further imply that the oldest populations were the smallest, although this must be tested further because of the complicated nature of drift time, one of the parameters used in the analysis. Since drift time also complicates other types of analysis, Schraiber anticipates that methods to fully account for the troublesome variable will allow development of a fuller picture of these results.

If validated, the increase in effective population size over time predicted by Schraiber’s method would be interesting to compare to archaeological information about ancient humans, especially because many current ideas hinge on a link between agriculture and the rise of larger, more interconnected societies. Perhaps new scientific evidence would put to rest some debates about ancient humans’ lives—but it would surely spawn even more questions, too.

CITATION:

Joshua G. Schraiber. Assessing the Relationship of Ancient and Modern Populations.
GENETICS, 208(1), 383-398.
DOI: 10.1534/genetics.117.300448
http://www.genetics.org/content/208/1/383

Corn feeds millions of people, and its low cost makes it particularly important in developing countries. However, it can’t be relied on as the sole source of protein for either humans or livestock because—like most cereals—corn is low in certain essential amino acids. In the 1960s, a type of corn was discovered with boosted levels of the essential amino acid lysine, which is typically found in small amounts in corn. But the variety had no practical use because it had a soft kernel that made it unfit for storage and transportation. To combat this problem, breeders developed Quality Protein Maize (QPM), a strain with restored kernel hardness—but there’s still room to improve corn’s nutritional profile.

In GENETICS, Planta and Messing describe how they constructed a strain that not only has more lysine, but also has an increased level of methionine, another essential amino acid found in insufficient amounts in corn. In addition to being more nutritious for humans, a strain with more methionine would make better feed for livestock; currently, synthetic methionine is often added to corn-based animal feed.

A key feature of QPM strains that makes them richer in lysine is a shift in the proportions of different proteins in the kernels, and the new strain is no exception. The lysine content is normally low in corn because most of the proteins in the mature kernel are from a group of proteins called zeins, the bulk of which contain few lysine residues. The original QPM strain has a mutation in the gene opaque-2 that decreases the production of many zeins, but there are other ways to achieve the same result.

Planta and Messing started with a strain carrying an RNAi gene that dampens the translation of RNA into a zein protein. Because this zein was known to be critical for kernel hardness, the strain had undesirably soft kernels, but the researchers serendipitously came upon a solution when they crossed the strain with their new high-methionine strain, called PE5. They had made PE5 by introducing a gene that increases flux through a biochemical pathway that produces sulfide, which is a precursor in the synthesis of methionine. To the researchers’ surprise, this cross produced a new strain that has a hard kernel and retains PE5’s superior methionine content, and it even has more lysine than its progenitors do, making it an excellent candidate for a new type of QPM.

Because the traits are dominant, it should be possible to add them to many existing strains of corn simply by crossing them with the new strain. Continued investigation of such enhanced corn strains is crucial—QPM strains are already in use, so an improved variety could make an even more significant dent in the malnutrition that plagues many regions where other protein sources are not readily available.

CITATION:
Planta, J.; Messing, J. Quality Protein Maize Based on Reducing Sulfur in Leaf Cells.
GENETICS, 207(4), 1687-1697.
DOI: 10.1534/genetics.117.300288
http://www.genetics.org/content/207/4/1687

Guest post contributed by members of the GSA Early Career Scientist Communications and Outreach Subcommittee.

In their bitter war with crop pests, farmers have two big guns: chemical pesticides and genetic engineering. But excitement has been building in the farming community for a new weapon that is unlike anything they’ve tried before, a pesticide 2.0. Highly selective and non-toxic, yet applied using the conventional methods of pesticide sprays, this approach exploits an ancient biological process to turn the pest’s own genes against it. But the new farming tool is just one use of a technology— RNAi —that is primed to fight a host of other major global challenges, including human disease. Farmers may well be at the frontlines of an RNAi revolution.

What is RNAi?

RNAi is a natural process that occurs in almost all organisms, from crop plants to insect pests to mice. Short for RNA interference, it is a form of protection against invading RNA. RNA is a chemical similar to DNA, and it helps translate the genetic code into action. Like DNA, it is found in every living thing and is highly specific to the particular species it came from. Some viruses even use RNA in place of DNA as their heritable code. Cells need to be able to recognize foreign RNA, such as from infecting viruses, which is where RNAi comes in. Two key RNAi proteins called Dicer and Slicer recognize, break apart, and destroy the invading RNA molecules.

This system was first discovered in the model worm Caenorhabditis elegans by Craig Mello, Andrew Fire, and their teams. Simply by injecting short pieces of RNA into their worms, they could “interfere” with the function of specific C. elegans genes. The scientists were able to target the genes of their choice; if they knew the gene’s DNA sequence they could design a corresponding RNA sequence that would set Dicer and Slicer on the attack. The superpower potential of RNAi was quickly appreciated and a Nobel Prize was awarded to Mello and Fire in 2006, just 8 short years after their original publication.

RNAi on the farm

Since its discovery, scientists have dreamed up a huge range of potential applications of RNAi, including sprayable solutions that silence selected genes in agricultural pests. To make such RNAi spray pesticides, genes specific to a particular pest are targeted with specially designed RNA molecules. Part of the beauty of this approach is that it can be directly deployed by farmers with no additional time or effort compared to traditional pesticide sprays. The RNA mix is either sprayed on the target insects or is taken up by the plants through their roots and then consumed by the insects. RNAi is also effective at lower doses than traditional pesticides. Combining RNAi with traditional pesticide treatments should reduce chemical inputs onto fields and reduce resistance of insects to those chemicals.

RNAi success stories are beginning to emerge from the field. The Asian citrus psyllid carries a pathogen that causes citrus greening disease, costing the citrus industry billions of dollars in lost crops and even more in lost jobs. Researchers targeted the insects by applying an RNAi pesticide to the trees, which was absorbed and spread to the stems and leaves. The insects then fed on the trees as nymphs, and all the adult insects died. Importantly, because the trees’ genomes are distinct from the insects’ genomes, the trees themselves are unaffected by the RNA.

Despite the high-tech origins of this approach, RNAi deployed this way does not permanently alter the genetic code of the plant, insect, or pathogen, so this technology is not classified as genetic modification. Even though genetically modified crops are well established by the scientific community as safe, consumer fear has continued to hold back acceptance of these products. Of course, there are also powerful ways to combine RNAi with genetic modification, such as enhancements to boost healthy carotenoids and beta-carotene in tomatoes and oranges, or a reduction in food sensitivity triggers such as lower-gluten wheat.

Importantly, an EPA panel in 2014 concluded that there is minimal likelihood of adverse effects arising from the use of RNAi in agriculture. Many RNAi applications are currently in development, and the USDA has recently approved a genetically modified corn that targets the devastating pest corn rootworm using RNAi. If this technology fulfills its promise to reduce our reliance on traditional pesticides and decrease crop yields lost to pests, it could increase global food production in the years to come.

RNAi in the clinic

But it is not just agriculture that can benefit. RNAi is being used in the same way to attack disease. The principles are the same: identify an unwanted target, such as a virus or even a cancer cell, and design an RNA molecule to target a protein specific to that target. RNAi could be used to treat disease without the negative side-effects common to many existing treatments. However, interest in this approach has waxed and waned in the years since the original RNAi discoveries of Fire and Mello.

Initially, there was a flurry of interest in medical applications, and almost 40 clinical trials are either active, recruiting, or completed. Although several have made it to the last stages of trials, none have yet been approved in humans. Among other factors, a major technological hurdle of how to get RNAi into the right human cells, caused the early excitement (and billions of dollars invested) to be eventually tempered into a period of reduced investment.

But recently, some of the technical challenges for delivery have been overcome for certain type of human diseases, and clinical trials are beginning to ramp up again. For example, partisiran, a potential treatment for familial amyloid polyneuropathy (FAP) which causes patients to lose the ability to use utensils, walk, and dress themselves, showed promising results from a phase 3 clinical trial. Patients who received partisiran showed reduced nerve damage compared to others who received the placebo. The drug targets the gene that causes FAP essentially turning it off and reducing levels of TTR protein which causes damage to nerves. If positive trial results continue, marketing of the drug is expected to begin in the U.S. this year, with European approval filings in 2018.

Although some of the initial unbounded optimism has become more realistic, the potential clinical benefits of RNAi remain substantial. Conventional drug treatments are commonly one-size-fits-all, whereas RNAi can be tailored to its target for precision medicine. Whether used by farmers or doctors, RNAi is proving that we can build more powerful tools by understanding the biology that underlies all life—from humans to worms.

Image credit: Genome Research Limited via Flickr. Shared under a [CC BY-NC-SA 2.0] license.

The authors:

Aleeza Gerstein

Alison Gerken