- Author: Kathy Keatley Garvey
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.
- Author: Kathy Keatley Garvey
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.”