Some examples of Nina V Fedoroff' s Scientific leadership.

Prehistoric GM Corn
Nina V. Fedoroff

Corn (maize) is arguably man's first, and perhaps his greatest, feat of genetic engineering. Its huge ears--each packed with firmly attached kernels filled with starch, protein, and oil--make it a food staple. Contemporary corn, unlike its wild grassy ancestor teosinte, can't survive without people because it can't disperse its own seeds. The origins of maize have long intrigued geneticists, but only recently have new molecular methods enabled evolutionary sleuths to pinpoint its origins and identify the genetic modifications (GMs) that enabled the radical transformation of teosinte into contemporary maize. On page 1206 of this issue, Jaenicke-Després, Doebley, and their colleagues (1) provide the latest chapter in this detective story and suggest that prehistoric people were quick to adopt GM corn.

Teosinte and corn (Zea mays) don't look much alike, but they are interfertile. Teosinte-corn hybrids arise in the wild but look so different from either parent that they were originally classified as a different species (Zea canina). In the 1920s, Beadle examined chromosomes in teosinte-corn hybrids and concluded that the two plants belonged to the same species, and even shared the same chromosomal order of genes...

So how, when, and where was teosinte transformed into maize? Beadle gave his mentor, Emerson, credit for the idea that just a few mutations changed teosinte into maize (4). Analyzing backcrossed maize-teosinte hybrids with molecular probes, Doebley's group came to a startlingly similar conclusion: The differences between maize and teosinte could be traced to just five genomic regions (5). In two of these regions, the differences were attributable to alternative alleles of just one gene: teosinte glume architecture (tga1) and teosinte branched (tb1), which affect kernel structure and plant architecture.

The tga1 gene controls glume hardness, size, and curvature (6). Teosinte kernels are surrounded by a stone-like fruitcase, assuring their unscathed passage through an animal's digestive tract, which is required for seed dispersal. But the plant's reproductive success is the consumer's nutritional failure. Not surprisingly, one of the major differences between maize and teosinte kernels lies in the structures (cupule and outer glume) enclosing the kernel. Maize kernels don't develop a fruitcase because the glume is thinner and shorter and the cupule is collapsed. The hardness of teosinte kernels comes from silica deposits in the glume's epidermal cells and from impregnation of glume cells with the polymer lignin. The maize tga1 allele supports slower glume growth and less silica deposition and lignification than does the teosinte tga1allele.

The tb1 locus is largely responsible for the different architecture of the two plants. Teosinte produces many long side branches, each topped by a male flower (tassel), and its female flowers (ears) are produced by secondary branches growing off the main branches. Modern corn has one main stalk with a tassel at the top. Its lateral branches are short and bear its large ears. Much of the difference is attributable to the tb1 gene, originally identified in a teosinte-like maize mutant. Mutations generally abrogate gene function, indicating that the maize allele acts by suppressing lateral shoot development, converting grassy teosinte into slim, single-stalked modern corn and male into female reproductive structures (7).

Knowing that this cluster of traits is controlled by just two genes makes it less surprising that genetic differences in these genes could render teosinte a much better food plant. Yet however useful to people, a tga1 mutation would have been detrimental to teosinte, making it more vulnerable to destruction in the digestive tract of the consumer and so less able to disperse its seeds. Thus, the only way this mutation could have persisted is if our ancestors propagated the seeds themselves. This implies that people were not only harvesting--and likely grinding and cooking--teosinte seeds before these mutations came along, but also were selecting for favorable features such as kernel quality and cob size. In turn, this suggests a "bottleneck" in corn evolution: Several useful GMs were brought together in a single plant and then the seeds from this plant were propagated, giving rise to all contemporary maize varieties. Such a prediction can be tested by calculating the number of generations and individuals it would take to account for the molecular variability present in contemporary maize. The results of such a test suggest a bottleneck for maize domestication of just 10 generations and a founding population of only 20 individuals (8). Did this happen once or many times? Because genetic differences arise at a fairly constant rate, this question can be answered by constructing family trees using similar sequences from different varieties of teosinte and contemporary maize. The results are unequivocal: All contemporary maize varieties belong to a single family, pointing to a single domestication event.

Knowing how quickly differences arise, how many there are today, and where the family of origin survives, it is possible to determine when--and where--it all started. The answer is that maize most probably arose from teosinte of the subspecies parviglumis in the Balsas River basin of southern Mexico roughly 9000 years ago (9). Recent redating of cobs from the Guilá Naquitz cave (about 500 km from the Balsas River basin) demonstrated that they were more than 6200 years old, providing archaeological support for the molecular findings (10, 11). These earliest corn cobs don't look much like those of modern corn, but they look even less like teosinte cobs (see the figure). They are tough and have several rows of tightly attached kernels, implying that the plants wouldn't have survived without people to detach and plant the seeds. By contrast, teosinte's reproductive structure, the rachis, falls apart when mature to release its hard seeds. Thus, even 6000 years ago, ancient maize cobs were already corn-like.

The GM corn spread far--and fast. Maize appears in the archaeological record of the southwestern United States more than 3000 years ago (12), and it is evident that cob size had already increased under selection. The Jaenicke-Després et al. study (1) examines the selection of traits that can't be observed in fossilized cobs...They report that alleles of these genes typical of modern corn were already present more than 4000 years ago, implying that plant architecture and kernel nutritive properties were selected early, long before corn reached North America.

The authors conclude that "... by 4400 years ago, early farmers had already had a substantial homogenizing effect on allelic diversity at three genes associated with maize morphology and biochemical properties of the corn cob." This suggests that once this special combination of GMs was assembled, the plants proved so superior as a food crop that they were carefully propagated and widely adopted, perhaps causing something of a prehistoric Green Revolution. It also implies that the apparent loss of genetic diversity following the introduction of high-yielding Green Revolution wheat and rice varieties in the 1960s and 1970s, and attending the rapid adoption of superior GM crops today, is far from a new phenomenon.

Science. 2003 Nov 14;302(5648):1158-9.

Transposable Elements As a Molecular Evolutionary Force
NINA V. FEDOROFF

So voluminous is the recent literature on transposable elements that it is difficult to imagine making an original observation; it seems that virtually anything that can be said about them, has been. My modest goal is to reexamine what we already know, viewing transposable elements as central players in a dynamic system of complex chromosome structure. McClintock often expressed the intuition that the genome responds to perturbation as an integrated system and acknowledged that we did not know how to think about such a higher level of integration. Although we still lack the analytic tools, there is a growing appreciation that organisms constitute complex, self-organizing systems whose properties can be understood through the study of interactions within and between networks of mutually interacting components, be they DNA sequences, proteins, or cells. Organisms must also be appreciated as historic entities. Today's genome reveals its evolution, which in turn is shaped and limited by the tools and materials available.

In an endeavor to see the familiar with new eyes, I begin by examining a property of eukaryotic genomes so familiar today that it is largely taken for granted: the presence of repetitive DNA. Whereas a high level of internal redundancy is appreciated as one of the most distinctive features of the complex genomes of higher eukaryotes, the theoretic and practical difficulties associated with the origin and maintenance of redundancy, in my view, have gone largely unrecognized and may be central to understanding contemporary genome structure. Redundant sequences can be either adjacent in the genome or dispersed. Different, albeit related, replication mechanisms give rise to each and pose different challenges to the stability and flexibility of the genome as a system. I will address the evidence that eukaryotes have special mechanisms to process duplications.

A rapidly growing body of data from genome characterization, cloning, and sequencing in a variety of organisms is making it increasingly evident that transposable elements have been instrumental in sculpting the contemporary genomes of all organisms. 1-7 The conversation has shifted from conjecture to fact. An understanding of genome evolution must necessarily include consideration of the role of transposable elements in the derivation of today's genomes. Transposable elements comprise a special category of reduplicated sequence whose inherent propensity for dispersal may be its most important property. I will review some of the mechanisms, both genetic and epigenetic, that regulate the movement of transposons and minimize their impact. Finally, the discussion must address the limits of the epigenetic regulatory systems, asking questions about the short- and long-term stability of eukaryotic genome structure.

My central theses are three: (1) that the distinctive feature of complex genomes is the existence of epigenetic mechanisms that permit extremely high levels of both tandem and dispersed redundancy, (2) that the special contribution of transposable elements is to modularize the genome, maintaining it in a structurally dynamic state despite increasing size and complexity, and (3) that the labilizing forces of recombination and transposition are just barely contained, giving a dynamic system of ever increasing complexity, verging on the chaotic.

Ann N Y Acad Sci. 1999 May 18;870:251-64.
Annals of the New York Academy of Sciences 870:251-264 (1999)

Nina Fedoroff
Huck Institute of Life Sciences, Pennsylvania State University
Evan Pugh Professor of Biology
Willaman Professor of Life Sciences, Biology Department
External Faculty, Santa Fe Institute
B.S., Syracuse University, Biology and Chemistry, summa cum laude (1966)
Ph.D., The Rockefeller University, Molecular Biology (1972)

Research Interests:
• Plant stress response
• Hormone signaling
• Transposable elements
• Epigenetic mechanisms

Plant stress response: A major project in the laboratory is investigating the responses of plants to biotic (pathogens) and abiotic (ozone, temperature, chemicals) stresses using DNA microarray gene expression profiling and reverse genetics. We have identified more than 1200 stress-modulated Arabidopsis genes and studying their expression under various conditions. The illustration shows the change in gene expression of 366 genes that are induced (red) or repressed (green) by ozone. Among the genes induced by various stresses are signaling genes, transcription factors, and effector genes that include enzymes that alter the cells structure and properties in response to stress. The signaling molecules include MAP kinases and receptor-like kinases. We are suppressing and overexpressing potential regulatory genes to identify the genes under their control. We want to understand the structure of the stress-response gene networks and to explores molecular genetic approaches to modifying the stress response (see Holter et al, 2000, 2001).

Hormone responses: The hyl1 Arabidopsis mutant (right) has a transposon insertion mutation in a gene that is involved in several hormonal signaling pathways, including those for abscisic acid, auxin and cytokinin. The mutant is affected in many growth parameters, including graviperception. It is not as sensitive to exogenous auxins and cytokinins as the wiltype, but it is hypersensitive to abscisic acid. The HYL1 protein binds to double-stranded RNA and localizes to the nucleus. The mutant is described in Lu and Fedoroff (2000). We are investigating how this protein affects hormone signaling.

Transposable elements: transposable elements or transposons were discovered in corn (maize) plants by the famous geneticist Barbara McClintock through classical genetic analysis of unstable mutations (for a brief history, see http://www.ergito.com or Fedoroff 2001). Maize transposons were cloned in our laboratory almost 20 years ago and are now widely used for insertional mutagenesis. We have created a database of several hundred Arabidopsis transposon insertion lines using a transposon tagging system developed in the laboratory (Smith et al., 1996; Raina et al., 2001). A map of the insertions is shown and the database can be searched at: http://sgio2.biotec.psu.edu/sr.

Epigenetic mechanisms: The maize Suppressor-mutator (Spm) transposon is epigenetically inactivated by methylation and encodes a protein, TnpA, which is capable of reversing the inactivation (Schläppi et al., 1994; Fedoroff et al., 1995). Using an inducible promoter to express TnpA, current experiments seek to understand how it demethylates the Spm promoter. Some ideas about plant transposon evolution are explored in Fedoroff (2000).



MENDEL IN THE KITCHEN: A Scientist's View of Genetically Modified Foods
Nina Fedoroff and Nancy Marie Brown.
Joseph Henry, (352p) ISBN 0-309-09505-1

Wall Street Journal Review
The Miracles of Modifying
By HENRY I. MILLER

November 11, 2004; Page D9
In the distant past, ruddy husbandmen tilled the earth, yielding the pure bounty of nature. Then scientists came along, and nature gave way to artifice with the use of unnatural hybrids and chemicals, and, inevitably, despoliation of the environment. Or so the story goes.
As it happens, agricultural practices have been "unnatural" for 10,000 years. With the exception of wild berries and wild mushrooms, virtually all the grains, fruits and vegetables in our diets (including "organic" ones) are, strictly speaking, genetically modified. Potatoes, tomatoes, oats, rice and corn, for instance, come from plants created -- during the past half-century -- by "wide cross" hybridizations that transcend "natural breeding boundaries."
This is only one of the many surprises in store for readers of "Mendel in the Kitchen" (John
Henry, 370 pages, $24.95) (Gregor Mendel, a 19th-century Austrian monk, first described the
basic laws of heredity that became the foundation for modern genetics.) Nina V. Fedoroff, a plant biologist, and her co-writer Nancy Marie Brown meticulously depict the past, present and future of genetics in agriculture. They mix didactic science (including diagrams reminiscent of a highschool biology textbook) with accounts of what farmers, naturalists, plant breeders and biologists have wrought over time. The saga brings rationality to the controversy now haunting the newest, most precise and most predictable manifestation of genetic modification -- gene-splicing.

...continues.

Nina V Fedoroff

Evan Pugh professor of biology and Willaman professor of life science at Pennsylvania State University
Scientific ideas can and must be tested and verified in the real world, in order for people to believe in them

What I wish everyone understood about science is that scientific ideas are like philosophical, political or religious ideas, in the sense that they are the products of people's minds and imaginations. But at the same time, scientific ideas are profoundly different from philosophical, political and religious ideas, because they can - and must - be tested and verified in the real world, in order for people to believe in them.

This means that scientific ideas are constantly changing, self-correcting and useful, as evidenced by the way they have allowed humans to grow food, build buildings and cities, travel, cure diseases, communicate and understand the universe. But I wish people understood that science as a way of living provides us with a viable social organising principle, that does not demand the kinds of rigid loyalty that is at the heart of much of the cultural and religious strife in the world. Science may therefore be the only way that human cultures can get beyond the social, cultural, economic and religious differences that underlie wars.