Societies to genes? And how do you get from there to here?
Noted honey bee geneticist Robert E. Page Jr., a UC Davis and Arizona State University emeritus professor and administrator, has authored a newly published, invited article in the journal Geneticson “Societies to Genes: Can We Get There from Here?” that highlights his three-decade scientific career.
“I was thrilled to be invited to write this perspectives/review of my scientific career; it is a collection of 30 years of single-minded focus on one question,” said Page, who is renowned for his research on honey bee behavior and population genetics, particularly the evolution of complex social behavior, and for his work on the first genomic map of the honey bee.
"The editors contacted me to write a perspectives/review that focuses on my own work, a study in complex adaptation,” Page related. “This is the first time they have done a perspectives article like this. I was, of course, honored. More than half of the work was done at UC Davis.”
“Understanding the organization and evolution of social complexity is a major task because it requires building an understanding of mechanisms operating at different levels of biological organization from genes to social interactions,” Page wrote in his abstract. “I discuss here, a unique forward genetic approach spanning more than 30 years beginning with human-assisted colony-level selection for a single social trait, the amount of pollen honey bees (Apis mellifera L.) store. The goal was to understand a complex social trait from the social phenotype to genes responsible for observed trait variation.”
“The approach,” Page wrote, “combined the results of colony-level selection with detailed studies of individual behavior and physiology resulting in a mapped, integrated phenotypic architecture composed of correlative relationships between traits spanning anatomy, physiology, sensory response systems, and individual behavior that affect individual foraging decisions. Colony-level selection reverse engineered the architecture of an integrated phenotype of individuals resulting in changes in the social trait. Quantitative trait locus (QTL) studies combined with an exceptionally high recombination rate (60 kb/cM), and a phenotypic map, provided a genotype–phenotype map of high complexity demonstrating broad QTL pleiotropy, epistasis, and epistatic pleiotropy suggesting that gene pleiotropy or tight linkage of genes within QTL integrated the phenotype. Gene expression and knockdown of identified positional candidates revealed genes affecting foraging behavior and confirmed one pleiotropic gene, a tyramine receptor, as a target for colony-level selection that was under selection in two different tissues in two different life stages. The approach presented here has resulted in a comprehensive understanding of the structure and evolution of honey bee social organization.”
Page, who received his doctorate in entomology (1980) from UC Davis, joined the UC Davis entomology faculty in 1989, and chaired the department from 1999-2004. In 2004, Arizona State University recruited him as founding director of its School of Life Sciences. His career advanced from dean of Life Sciences, to vice provost and dean of the College of Liberal Arts and Sciences, to university provost. Today he holds the titles of ASU provost emeritus, ASU Regents professor emeritus, and UC Davis distinguished emeritus professor, an award bestowed in 2019.
For 24 years, from 1989 to 2015, Page maintained a UC Davis honey bee-breeding program, managed by bee breeder-geneticist Kim Fondrk at the Harry H. Laidlaw Jr. Honey Bee Research Facility. Together they discovered a link between social behavior and maternal traits in bees.
In his article, he mentions: "I studied the behavioral genetics of pollen storage in honey bees for more than 30 years. The effort was collective with my technician and colleague Kim Fondrk and numerous students and postdoctoral researchers. We used a forward genetic approach and employed bidirectional, human-assisted selection that resulted in the establishment of two strains that varied in their expression of a social phenotype. We focused on just one trait, the amount of pollen stored in the nest, a social trait that is a consequence of the interactions of thousands of bees. There are about 10–40 thousand worker bees in a honey bee colony, depending on the time of year. Honey bee colonies have a reproductive division of labor where the single queen normally lays the eggs while the workers are facultatively sterile."
"Young larvae produce pheromones (chemical signals) that stimulate some of the foragers to collect pollen (Traynor et al. 2015)," he explained. "The amount of pollen stored, the number of cells that are full, affects the number of larvae that are raised and inhibits pollen foraging, thus stored pollen is regulated (Fewell and Winston 1992). Returning pollen foragers perform recruitment dances that communicate the distance and direction from the nest to their pollen sources. Other bees attend the dances and are recruited. So, the amount of stored pollen is dependent on the interactions of thousands of individual adults and larvae and is not a phenotypic trait of any individual—it is a social phenotype."
Page has authored than 250 research papers, including five books: among them, The Spirit of the Hive: The Mechanisms of Social Evolution, published by Harvard University Press in 2013. His most recent book is The Art of the Bee: Shaping the Environment from Landscapes to Societies, published by Oxford University Press 2020. (See news release on why bees are both artists and engineers.)
Page is a highly cited author on such topics as Africanized bees, genetics and evolution of social organization, sex determination, and division of labor in insect societies.
Newly published research by a team of Germany-based honey bee geneticists, collaborating with Robert Eugene (“Rob”) Page Jr., of Arizona State University/University of California, Davis, offers new insights in the ability to modify and study the chromosomes of honey bees.
Martin Beye, a professor at the University of Düsseldorf, Germany and a former postdoctoral fellow in Page's lab at UC Davis, served as the lead author of the research, “Improving Genetic Transformation Rates in Honeybees,” published in Scientific Reports in the journal Nature.
The researchers accomplished the work in Beye's lab in Germany and the Page labs.
“The significance of this paper lies in the ability to modify the chromosomes of honey bees and study the effects of individual genes,” said Page, former professor and chair of the UC Davis entomology department before capping his academic career as the Arizona State University provost.
“The honey bee genome,” Page explained, “is composed of about 15,000 genes, each of which operates within a complex network of genes, doing its small, or large, share of work in building the bee, keeping its internal functions operating, or helping it function and behave in its environment. The ability to transform, change, genes, or add or delete genes from chromosomes of bees, has been exceptionally challenging and the effort spans decades. Martin tackles problems such as this. He takes on the most challenging genetic problems and solves them.”
Beye was the first to map the major sex-determining gene for honey bees, considered one of the most important papers ever published on honey bee genetics. He “then moved on and developed a way to implement gene editing, being able to alter single genes within the genome,” Page related. “Now he has developed a method to introduce new genetic material into the honey bee.”
In their abstract, the six-member team wrote that “Functional genetic studies in honeybees have been limited by transformation tools that lead to a high rate of transposon integration into the germline of the queens. A high transformation rate is required to reduce screening efforts because each treated queen needs to be maintained in a separate honeybee colony. Here, we report on further improvement of the transformation rate in honeybees by using a combination of different procedures.”
Specifically, the geneticists employed a hyperactive transposase protein (hyPBaseapis), tripling the amount of injected transposase mRNAs. They injected embryos into the first third (anterior part) of the embryo. These three improvements together doubled the transformation rate from 19 percent to 44 percent.
“We propose that the hyperactive transposase (hyPBaseapis) and the other steps used may also help to improve the transformation rates in other species in which screening and crossing procedures are laborious,” they wrote in their abstract.
For their research, the scientists chose feral Carniolan or carnica colonies. Carniolans, a darker bee, are a subspecies of the Western honey bee, Apis mellifera.
Beye joined the Page lab in 1999 as the recipient of a Feodor Lynen Research Fellowship, an award given to the brightest young German Ph.Ds to provide an opportunity for them to work in the laboratories of U.S. recipients of the Alexander von Humboldt Research Prize. Page, who won the Humboldt Prize in 1995, continues to focus his research on honey bee behavior and population genetics, particularly the evolution of complex social behavior.
Following his postdoctoral fellowship, Beye returned to the Page labs at UC Davis and ASU as a visiting scientist. (link to https://www.ucdavis.edu/news/honeybee-gene-find-ends-150-year-search ) Beye spoke at UC Davis this spring as part of his Humboldt-funded mini sabbatical, the guest of Page and hosted by the Department of Entomology and Nematology. During his visit, he and UC Davis bee scientist Brian Johnson developed collaborative projects that they will begin in the spring of 2019. “This is exactly what the Alexander von Humboldt foundation wants – to build and extend interactive networks of researchers,” Page commented.
About Robert Page Jr.
Noted honey bee geneticist Robert Page Jr., author of The Spirit of the Hive: The Mechanisms of Social Evolution, published by Harvard University Press in 2013, recently received the Thomas and Nina Leigh Distinguished Alumni Award, UC Davis Department of Entomology and Nematology.
Page received his doctorate in entomology from UC Davis and served as a professor and chair of the UC Davis entomology department before capping his academic career as the Arizona State University (ASU) provost. He maintained a honey bee breeding program managed by bee breeder-geneticist Kim Fondrk at the Harry H. Laidlaw Jr. Honey Bee Research Facility, UC Davis, for 24 years, from 1989 to 2015.
Now provost emeritus of ASU and Regents Professor since 2015, he continues his research, teaching and public service in both Arizona and California and has residences in both states. He plans to move to California in December.
Page focuses his research on honey bee behavior and population genetics, particularly the evolution of complex social behavior. One of his most salient contributions to science was to construct the first genomic map of the honey bee, which sparked a variety of pioneering contributions not only to insect biology but to genetics at large.
The highly acclaimed research published in Current Biology that cracked the 200-year secret of complementary sex determination in honey bees is rooted right here, right here at UC Davis.
Arizona State University Provost Robert E. Page, Jr., emeritus professor and former chair of the UC Davis Department of Entomology, and two other UC Davis-affiliated scientists are among the key members of the scientific team from the United States, Germany and France who published their work, “Gradual Molecular Evolution of a Sex Determination Switch in Honeybees through Incomplete Penetrance of Femaleness" in the prestigious journal.
The ground-breaking research shows that five amino acid differences separate males from females.
Lead author is Martin Beye, who was a Fyodor Lynen Fellow in Page's UC Davis lab from 1999 to 2000. He's now an evolutionary geneticist at the University of Duesseldorf, Germany. Another co-author is Michael "Kim" Fondrk, bee breeder-geneticist, who tends Page's research bees at the Harry H. Laidlaw Jr. Honey Bee Research Facility, UC Davis. Fondrk provided the genetic material from crosses from Page's bees.
Page traces the bee puzzle "back to Johann Dzierson in the mid-1800s through Mendel, through Harry Laidlaw to me and to my former postdoc at Davis, Martin Beye."
“Much of the work was done at UC Davis beginning in 1990,” said Page. While at UC Davis, "Martin began the sequencing and characterization of the csd gene; the paper was eventually published as a cover article in Cell."
Said Fondrk: “This project was a long time in making; it began soon after our Cell paper was published in 2003. First we needed to assemble variation for alleles at the sex locus, by collecting drones from many different, presumably unrelated queens, and mating one drone each through an independently reared set of queens using instrumental insemination (which was Fondrk's task). "Then a second set of crosses was made to identify and isolate individual sex alleles. The progeny that resulted from this cross were taken to Germany where Martin Beye’s team began the monumental task of sequencing the sex determination region in the collected samples.”
Silesian monk Johann Dzierson began studying the first genetic mechanism for sex determination in the mid-1800s. Dzierson knew that royal jelly determines whether the females will be queen bees or honey bee colonies, but he wondered about the males.
Dzierson believed that the males or drones were haploid--possessing one set of chromosomes, a belief confirmed in the 1900s with the advent of the microscope. In other words, the males, unlike the females, came from unfertilized eggs.
“However, how this system of haplodiploid sex determination ultimately evolved at a molecular level has remained one of the most important questions in developmental genetics,” Coulombe pointed out.
Coulombe quoted Page: “There has to be some segment of that gene that is responsible in this allelic series, where if you have two different coding sequences in that part of the gene you end up producing a female. So we asked how different do two alleles have to be? Can you be off one or two base pairs or does it always have to be the same set of sequences? We came up with a strategy to go in and look at these 18-20 alleles and find out what regions of these genes are responsible among these variants.”
“What the authors found,” wrote Coulombe, “was that at least five amino acid differences can control allelic differences to create femaleness through the complementary sex determiner (csd) gene – the control switch.”
Page explained: “We discovered that different amounts of arginine, serine and proline affect protein binding sites on the csd gene, which in turn lead to different conformational states, which then lead to functional changes in the bees – the switch that determines the shift from female to not female.”
In addition to Beye, Page and Fondrk, other co-authors are Christine Seelmann and Tanja Gempe of the University of Duesseldorf; Martin Hasslemann, Institute of Genetics at the University of Cologne, Germany; and Xavier Bekmans with Université Lille, France
Page, recognized as one of the world’s foremost honey bee geneticists, is a highly cited entomologist who has authored more than 230 research papers and articles centered on Africanized bees, genetics and evolution of social organization, sex determination and division of labor in insect societies. His work on the self-organizing regulatory networks of honey bees is featured in his new book, The Spirit of the Hive: The Mechanisms of Social Evolution, published in June 2013 by Harvard University Press.
Page received his doctorate in entomology from UC Davis in 1980. He left his faculty position at Ohio State University in 1989 to join the UC Davis Department of Entomology faculty. Page chaired the UC Davis department from 1999 to 2004 when ASU recruited him as the founding director and dean of the School of Life Sciences, an academic unit within College of Liberal Arts and Science (CLAS). Page was selected the university provost in December. He had earlier served as the vice provost.
The news story is gathering lots of interest, and rightfully so. It's a piece of a puzzle that went missing for 200 years.
Said Extension apiculturist Eric Mussen of the UC Davis Department of Entomology and Nematology, who was not involved in the research but knows many of the scientists and their work: "Once again, the studies by Dr. Rob Page and his colleagues have unraveled another mystery of honey bee development. It would be interesting if someone investigated the same type of sexual dimorphism in other hymenopterans to determine if they all use the same, ancient-based mechanism.”
That's the title of a newly published book written by Robert E. Page Jr., one of the world's foremost honey bee geneticists.
In his 224-page book, published by Harvard University Press, Page sheds light on how 40,000 bees, "working in the dark, seemingly by instinct alone, could organize themselves to contstruct something as perfect a a honey comb."
Page, former professor and chair of the UC Davis Department of Entomology, marvels at how bees can accomplish these incredible tasks. In synthesizing the findings of decades of experiments, he presents "a comprehensive picture of the genetic and physiological mechanisms underlying the division of labor in honey bee colonies and explains how bees' complex social behavior has evolved over millions of years," according to the Harvard University flier.
Page, now vice provost and dean of the Arizona State University's College of Liberal Arts and Sciences and Foundation Professor of Life Sciences, still keeps his specialized stock of honey bees at the Harry H. Laidlaw Jr. Honey Bee Research Facility at UC Davis. Bee breeder-geneticist Michael “Kim” Fondrk, who worked with Page at Ohio State University, UC Davis and ASU, manages the stock.
In his book, Page talks about the coordinated activity of the bees and how worker bees respond to stimuli in their environment. The actions they take in turn alter the environment, Page says, and "so change the stimuli for their nestmates. For example, a bee detecting ample stores of pollen in the hive is inhibited from foraging for more, whereas detecting the presence of hungry young larvae will stimulate pollen gathering."
Division of labor, Page says, is an inevitable product of group living because "individual bees vary genetically and physiologically in their sensitivities to stimuli and have different probabilities of encountering and responding to them."
Page, who received his doctorate in entomology at UC Davis in 1980, served as an assistant professor at Ohio State University before joining the UC Davis Department of Entomology in 1989. He chaired the department for five years, from 1999 to 2004.
In 2004--the year Page retired from UC Davis--ASU recruited him as the founding director and dean of the School of Life Sciences. At the time, his duties included organizing three departments—biology, microbiology and botany, totaling more than 600 faculty, graduate students, postdoctoral fellows and staff--into one unified school.
As its founding director, Page established the school as a platform for discovery in the biomedical, genomic and evolutionary and environmental sciences. He also established ASU’s Honey Bee Research Facility.
Page is a highly cited author on such topics as Africanized bees, genetics and evolution of social organization, sex determination, and division of labor in insect societies.
Add this one to the list: The Spirit of the Hive.
The ESA Governing Board today announced the new fellows, who will be recognized Nov. 11, 2012 at the ESA’s annual meeting in Knoxville, Tenn.
Page, the vice provost and dean of the College of Liberal Arts and Sciences, Arizona State University, Tempe, since July 2011, is a pioneer in the field of evolutionary genetics and the social behavior of honey bees.
Page did much of his research at UC Davis. He received his doctorate in entomology at UC Davis in 1980, learning from his major professor Harry H. Laidlaw Jr. (for whom the UC Davis bee research facility is named). He then joined The Ohio State University faculty before returning to UC Davis as a faculty member in 1989.
He chaired the UC Davis Department of Entomology from 1999 to 2004.
Page, who studies the evolution of complex social behavior in honey bees, from genes to societies, left UC Davis in 2004 to be the founding director of the new School of Life Sciences. Arizona State University, where he built a Social Insect Research Group that is now recognized worldwide.
Page was trained as an entomologist, evolutionary population geneticist, classical animal breeder, and mechanistic behaviorist, according to a news release issued by the ESA. "This training has defined his research approach of looking at the genetics and evolution of complex social behavior. He has taken a vertical approach to understanding the mechanisms of honey bee social foraging and how it evolves."
His work is contained in more than 225 research articles. Page has also co-edited three books and authored or co-authored two. Page is a highly cited ISI (Institute for Scientific Information) author in plant and animal science. He is a fellow of the American Association for the Advancement of Science (AAAS) and an elected member of the American Academy of Arts and Sciences, the German National Academy of Science, and the Brazilian Academy of Science. In 1995 he was awarded the Alexander von Humboldt Research Prize by the government of Germany.
Although Page resides in Arizona, his research bees are UC Davis-based residents. Bee breeder-geneticist Michael “Kim” Fondrk, who worked with Page at Ohio State University, UC Davis and ASU, manages the specialized genetic stock, which today includes 90 hives.
Of the 90 hives, about 70 have instrumentally inseminated queens as part of their pollen-hoarding breeding research program.
Back in 2006, Page told us: "Davis is still home to me. I raised my family there, my closest friends and colleagues are still in the entomology department there. I still feel very strong attachments.”
Former department chair Robert Washino remembers him fondly. He recently recalled that "Rob chose to return to UC Davis in 1989 to be with his former major professor (Harry H. Laidlaw Jr.). He later cared for him and his wife, Ruth, in their declining years. We all remember Rob’s scholarly side and his humanitarian side.”
Page joins three other UC-affiliated entomologists in the ESA Fellows Class of 2012: Joseph Morse, professor of entomology at UC Riverside; Henry H. Hagedorn, who received his doctorate in entomology from UC Davis in 1970; and R. Michael Roe, who trained at the UC Davis Department of Entomology from 1981 to 1984 as a National Institutes of Health fellow in cellular and molecular biology.
And interestingly enough, Page is following in the footsteps of Harry H. Laidlaw Jr., who himself was elected an ESA fellow in 1991.
With the addition of Page, the UC Davis Department of Entomology now has 16 fellows who are current or former faculty members. The first was Richard M. Bohart (1913-2007), for whom the Bohart Museum of Entomology is named. He received the honor in 1947. Fifteen others followed: Donald McLean, elected in 1990; Harry H. Laidlaw Jr. (1907-2003), 1991; John Edman, 1994; Robert Washino, 1996; Bruce Eldridge, 2001; William Reisen, 2003; Harry Kaya, 2007; Michael Parrella and Frank Zalom, 2008; Walter Leal, 2009; Bruce Hammock and Thomas Scott, 2010; James R. Carey and Diane Ullman, 2011, and now Robert E. Page Jr., 2012.