Special Seminar at UC Davis:
Queensland University of Technology
Hormones and the Holobiont:
Origins and some implications of hologenome theory.
August 6, 2019
11:30 am – 1:00 pm
Below are some materials provided by Dr. Jefferson in relation to his talk
Multicellularity requires coordination of spatially distal cells and temporally diverse actions. In vertebrates, much of this is mediated by hormones, frequently steroids, most of which are excreted through apocrine, exocrine and endocrine secretions as inactive conjugates of glucuronic acid or sulfate. Myriad, diverse microbiota populate the epithelia and through cleavage by diverse glucuronidases (GUS) and arylsulfatases (ARS), release the active form of the hormone which can then be resorbed or presented with altered kinetics, bioactivity and concentrations to diverse sites of action. The microbial populations thus modulate hormone action.
From 1980-1990, we developed and distributed GUS from E. coli as a reporter gene for plant, fungal and animal transgenesis and for microbial ecology studies. In our efforts to improve its efficacy, we explored glucuronide operon function in enteric microbes, and sought natural GUS variants in populations of soil, water, epithelial or fecal microbes that might have improved properties. We made field trips to Africa to isolate fecal and environmental microbes that were unlikely to be present due to human action and contamination. In parallel we revisited neglected literature on the function of the enzymes in vertebrate biology. In combination with stunning advances in microbial discovery and identification (e.g. David Ward’s & Steve Giovannoni’s discoveries of the ubiquity of uncultured microbes), and some neglected industrial R&D we were led to a major rethink on much of our framework around biology and evolution, science and society. This led to articulation of the hologenome theory of evolution at Cold Spring Harbor in 1994 and the extended proposal that hormone activity in metazoa and metaphyta was modulated by the dynamic population structures of associated microbes. The pleiotropic and powerful effect that hormone modulation could have to reorient and impact virtually all fitness-related traits, and indeed all reproductive activity of plants and animals, stimulated new insights into living systems. In this presentation, I’ll review the coincidences and congruences that led to the theory and some of the possible implications for science and society, in the form of some conjectures.
Did the advent of agriculture and the concomitant rise in sedentary and concentrated populations cause massive inbreeding depression of the microbiome and become the origin of disease – plant, animal and human – as dysbiosis? Is the germ theory of disease opportunistically right but structurally wrong? Did commensalism and community tactility/touching – the hallmarks of social behavior – cause harmonization and reinforce convergent microbial populations and thus congruent hormone action and hence behavior? Has all of evolutionary thought been compromised by scale bias? Is it reasonable that the logic of evolution is embedded in macro-organisms (e.g. anything we can see) rather than the vast majority of all living systems that we can’t? Is the holobiont – in the case of all systems that have experienced the post agricultural microbial collapse – really a merobiont, with at best metastable populations that do not reflect an empirical steady state? Is Darwin’s natural selection an ‘edge-case’ in evolution, working well at medium physical and temporal scales, but not truly reflecting the primacy of information-state persistence that could describe microbial life? Could the hologenome theory and the microbiome provide the missing mechanism to the late 19th century’s other great evolutionist – now largely forgotten – Pyotr Kropotkin, who proposed ‘Mutual Aid: a factor in evolution” in 1902? Could the real driver of evolution not be replication and reproduction, but persistence and pooing? Can the role of macro-apobionts be largely as dynamic scaffolds to recruit, select, nurture, amplify and disseminate microbial populations?
Richard Jefferson is a Professor of Biological Innovation at the Queensland University of Technology (QUT) and founder and CEO of Cambia & The Lens. Richard received a PhD in Molecular, Cellular and Development Biology from University of Colorado at Boulder in 1985, where he developed the glucuronidase (GUS) system as a molecular heuristic tool for transgenesis, developmental and ecosystem studies.
During his NIH postdoc at the Plant Breeding Institute in Cambridge, UK, Richard adapted GUS for agricultural biotechnology and pioneered an open source paradigm by distributing the toolkits to hundreds of labs around the world before publication. This enabled the genetic engineering of virtually all commercial crops, and is now the most cited molecular technology in agriculture. In 1987, with colleagues at PBI, Richard led the world’s first field release of a biotech food crop. In 1989 Richard was appointed the first Molecular Biologist for the United Nations FAO/IAEA in Vienna, and in 1991 founded Cambia, an autonomous global social enterprise to democratize science- enabled problem solving. Besides Cambia’s role in inventing and distributing open source enabling technologies it runs Lens.org, now the longest operating, largest and most comprehensive free, open and secure platform for scholarly and patent discovery, analytics and metrics.
Based on work done on diverse microbial GUS and arylsulfatases since 1980, and their essential role in modulating hormone action in the holobiont, Richard proposed the landmark hologenome theory of evolution in 1994 at Cold Spring Harbor. He was the first to describe the role of the microbiome as the driver of biological evolution, and its role in understanding and optimizing performance of biological systems. In 1997, Richard proposed the concept of ecotherapeutics as a strategy for modulating agriculture and health systems performance by adjusting population structures of microbial constituents. The hologenome theory has profound implications for how we think about ourselves, living systems, the origin of disease, the origins of social behavior and even social institutions in innovation.
Richard is an ‘Outstanding Social Entrepreneur’ of the Schwab Foundation and a regular panelist at the World Economic Forum’s (WEF) Davos annual meetings and Summits. Richard served on the WEF Global Agenda Council on Intellectual Property and the Global Agenda Council on the Economics of Innovation. He was named to Scientific American’s list of the world’s 50 Most Influential Technologists. His work has featured in countless media, including The Economist, New York Times, Newsweek, Red Herring, Nature, Science, Nature Biotechnology.
UPDATE – posting my notes for his talk. They are hand drawn notes on paper. I will try to write up something later but really really busy right now so it will have to wait