Profile of James A. Birchler

PROFILE PROFILE Profile of James A. Birchler Farooq Ahmed Freelance Science Writer Food and fuel: two key elements of human in ethnobotanist Charles Arzeni. Formerly prosperity and survival that have grown a botanist in Africa, Arzeni made up for the scarce as the global population has continued university’s lack of research by sponsoring to grow. According to the World Bank and field trips to far-flung locales like the Ama- the International Monetary Fund, droughts zon rainforest in Colombia. Notes Birchler, and increased demand have led to unaccept- “It’s only because of Arzeni that I went to ably high rates of child and maternal mortality graduate school.” Birchler remained in the across the world (1). Increased fuel costs, the heart of the Midwest and attended Indiana organizations say, have also contributed to University, two and a half hours east of the rising price of staples like corn and soy- where he went to college. bean oil (2). During his first semester in graduate A former Illinois farm boy, James Birchler school, Birchler received a letter informing has developed a technique that may help him to enter the draft for the Vietnam War. tackle these seemingly intractable issues. Because he had received an earlier defer- Now a Curators’ Professor at the University ment, he was nearly assured of being draf- of Missouri and a recently elected member ted. Then, on December 31, 1972—the day of the National Academy of Sciences, Birch- before he was eligible—President Richard ler integrated decades of research on plant Nixon suspended the draft, which was never genetics to create synthetic maize chromo- reinstated. Birchler plants corn in the summer plot at Indiana Univer- somes. These chromosomes, which propa- sity in 1976. Photograph by Edith Birchler. gate naturally in corn, can be outfitted with Inverse Effect and Dosage genes for drought tolerance, biofuel produc- Compensation lence of dosage compensation in maize and tion, or other beneficial properties to pro- Having escaped the Vietnam War, Birchler discovered that it relied on the inverse dos- duce stable lines of bioengineered crops that focused on plant genetics at Indiana, work- may help address some of the global crises ing with Drew Schwartz, whom he credits age effect (4, 5). The effect occurs when there that threaten us. with providing an atmosphere of lively sci- is a negative correlation between gene ex- entific discussion. “That led to research that pression and chromosomal dosage. Scientist Farmers we’re still pursuing, because, in Schwartz’s Birchler was born in Red Bud, IL, southeast Facts About Flies lab, I started changing the dose of chromo- At first, Birchler’sworkwasdismissedasa of St. Louis. His mother and father, both some arms in maize and studying the ex- teachers, ran the family farm. They grew quirk of plant genetics or an experimental pression levels of different genes.” artifact. He joined Ed Grell at Oak Ridge corn, soybeans, and wheat, and raised beef He carried out these experiments by ex- cattle. Birchler credits his upbringing for his National Laboratory in Tennessee as a post- “ ploiting a quirk of maize genetics. Corn has doctoral fellow to recapitulate his findings in early interest in science. Ihadthetypical 10 primary chromosomes called A chromo- fl “ farm-boy chores of plowing fields, cutting fruit ies. Ed was a fountain of facts about somes and a genetically inert supernumerary fl fi hay, and feeding cows. That environment y genetics and the history of the eld. He B chromosome of variable number. Remark- fi gave me an early exposure to zoology and was one of the rst people to show that, if ably, the B chromosome enters only half of botany,” he says. “I could identify all the dif- you varied the gene encoding an enzyme in maize sperm cells. Birchler manipulated the Drosophila ferent species of trees on the farm—with and , you got a proportional amount dosage of chromosomal segments in maize — without their leaves.” He went to high school of gene product so he seemed like a great by using stocks that have regions of the A ” in nearby Sparta, IL, and attended college at choice for me as a postdoctoral mentor. chromosome attached to the B chromosome fi Eastern Illinois University to study education. By reproducing his ndings in another in a genetic trick called B-A translocation. “In high school, I had taken a biology class species, Birchler demonstrated that varying Birchler observed that the magnitude of and had gotten quite interested in the concept chromosome dosage routinely produced the the change in gene expression could be ei- of evolution. At the time, Eastern didn’thave inverse effect and dosage compensation. (6) ther a direct or an inverse correlation with “ fl a biology department, so I majored in botany The y research illustrated the generality of chromosomal dosage (3). Furthermore, in- ” and minored in zoology.” By attending col- the phenomenon, he says. Birchler then creasing a gene’s amount on a chromosome joined Kenneth Paigen’slaboratoryatthe lege, Birchler received a deferment from being drafted to fight in the Vietnam War. did not always increase its level of ex- University of California in Berkeley, where pression. This finding, called dosage com- Deferred Draft pensation, had been thought to occur ex- This is a Profile of a recently elected member of the National At Eastern Illinois, which had no undergrad- clusively in the sex chromosomes of animals. Academy of Sciences to accompany the member’s Inaugural Article uate research program, he found a mentor Birchler went on to demonstrate the preva- on page 14746 in issue 37 of volume 109. www.pnas.org/cgi/doi/10.1073/pnas.1221539110 PNAS | February 19, 2013 | vol. 110 | no. 8 | 2687–2689 Downloaded by guest on September 27, 2021 he continued studying Drosophila genetics. the molecular biological level, searching for Paigen focused mainly on mouse genetics, the mechanisms. which provided Birchler exposure to an- As an offshoot of the dosage studies, re- other experimental model. searchers Manika Pal-Bhadra and Utpal In 1985, he accepted a position in the Bhadra, in Birchler’s group, discovered department of organismic and evolutionary the phenomenon of transgene silencing in biology at Harvard University. “Iliketojoke Drosophila, which at the time had been that it was the only place I could find a job,” thought to occur only in plants. They ob- he says. “Even though I had a longstanding served that a family of proteins that help interest in evolution,” Birchler continues, “I package DNA, known as Polycomb group had not had any formal training in the sub- proteins, played an integral role in silencing ject, so Harvard was an excellent learning genes in flies and that the mechanism used experience.” small RNA (12, 13). The repressive Poly- The inverse effect. The eyes of Drosophila carrying the comb complex associated with transgene Fruit and Flies white-apricot allele of the white eye color gene with sequences, whereas mutations in the genes With his own laboratory, Birchler was free different functional doses of the Inverse regulator-a (Inr- that process small RNAs reversed the si- a) gene. Clockwise from top: one, two, and three func- to pursue regulatory mechanisms in the ge- lencing effect. Further studies demonstrated nomes of both maize and Drosophila. “Over tional dose(s) of Inr-a. The amount of pigment from the white gene is inversely proportional to the dosage of that the regulation of Drosophila hetero- the next 15 years, in an effort initiated by functional alleles of Inr-a. Photograph by Weiwu Xie. chromatin, the part of a chromosome that my former postdoc Leonard Rabinow, we is normally inactive, involved related molec- were able to reduce the gene dosage effects of them. (8) “They all have some kind of ular mechanisms (14). found with chromosomal segments to single regulatory function and are mainly tran- genes.” Regulatory and signal transduc- Corn Paintings scription factors, chromatin proteins, and tion genes, they found, caused both the While developing genetic trickery in maize, fi components of signal transduction path- ’ inverse and direct effects (7, 8). These nd- ” Birchler s group also examined chromosome ways. In maize, they varied the ploidy of the structure. Research by postdoctoral fellow ings strongly suggested that dosage effects — genome the copy number of the whole set Akio Kato, now of Kyoto Prefectural Uni- were a general property of genetic regulatory — mechanisms. of chromosomes in a species and com- versity, and graduate student Jonathan Lamb During this time, graduate student Mark pared it to varying individual chromosomes led to a method that uses fluorescence to “ Alfenito, in Birchler’s group, also investigated or other genomic pieces. (10) When you distinguish each of the 10 chromosomes of the supernumerary B chromosome in maize, varied pieces, you uncovered modulations maize, which they identified by targeting and identified DNA repeats specifictothe that were quite prevalent. On the other repeated nucleotide sequences on each chro- centromere (9). This discovery inspired work hand, varying the whole genome gave much mosome (15). Birchler explains that this that eventually led to the construction of less of a change.” technique, called chromosome painting, plant artificial chromosomes, which can help Birchler’s Inaugural Article further expli- “produced an explosion of research in our combine beneficial genetic properties onto a cates the gene balance hypothesis (11). To- lab and helped us localize individual genes single chromosome that is independent from gether with Reiner Veitia, a human geneticist in maize and study, among other things, the the rest of the genome. at Institut Jacques Monod and Université distribution and behavior of transposons.” In 1991, the University of Missouri re- Paris Diderot in Paris, he synthesized lines Using this technique, former postdoctoral cruited Birchler to their flagship Columbia of evidence from distinct areas of biology fellow Fangpu Han, now at the Chinese campus.

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