Thomas Flatt
Professor
thomas.flatt@unifr.ch
+41 26 300 8833
https://orcid.org/0000-0002-5990-1503
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Professor,
Department of Biology
PER 23 bu. 1.01
Ch. Du Musée 15
1700 Fribourg
Professor
Biography
Thomas Flatt is Professor of Evolutionary Biology in the Department of Biology at the University of Fribourg. His research interests are the genetic and genomic basis of adaptation, population genetics, and the evolution of life histories and aging, with a focus on the mechanisms underlying trade-offs between fitness components. Most recently, his work has focused on the role of chromosomal inversion polymorphisms and balancing selection in adaptation. Thomas received his M.Sc. in Zoology (Population Biology) from the University of Basel in 1999 (supervised by Stephen C. Stearns), for work done at the University of Sydney with Richard Shine, and his Ph.D. in Ecology & Evolution from Fribourg in 2004 (supervised by Tadeusz J. Kawecki). Between 2004 and 2008, he was a postdoctoral fellow at Brown University with Marc Tatar and a visiting postdoc with Neal Silverman at UMass Medical School, funded by fellowships from the Swiss National Science Foundation (SNSF) and Roche Research Foundation. Prior to taking up his position in Fribourg in 2017, he was a SNSF Professor in the Department of Ecology & Evolution at Lausanne (2012-17), a Fellow at the Wissenschaftskolleg Berlin (2012), a faculty member of the Vienna Graduate School of Population Genetics and a tenured group leader at the Institute of Population Genetics in Vienna (2009-12). Between 2018 and 2021 he held a DFG Mercator Fellowship and Visiting Professorship at the University of Münster. Together with Josefa Gonzalez (Barcelona) he co-leads the European Drosophila Population Genomics Consortium (DrosEU). He currently serves on the editorial board of the Proceedings of the Royal Society B, as an elected member of the National Research Council of the Swiss National Science Foundation and as a member of several scientific advisory boards.
Research and publications
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Publication list
130 publications
From whole bodies to single cells: A guide to transcriptomic approaches for ecology and evolutionary biology
Katja M. Hoedjes, Sonja Grath, Nico Posnien, Michael G. Ritchie, Christian Schlötterer, Jessica K. Abbott, Isabel Almudi, Marta Coronado‐Zamora, Esra Durmaz Mitchell, Thomas Flatt, Claudia Fricke, Amanda Glaser‐Schmitt, Josefa González, Luke Holman, Maaria Kankare, Benedict Lenhart, Leeban Yusuf, Dorcas J. Orengo, Rhonda R. Snook, Vera M. Yılmaz, Molecular Ecology (2024) | Journal articleGermline proliferation trades off with lipid metabolism in Drosophila
Martin Kapun, Marisa Rodrigues, Chantal Dauphin-Villemant, Margot Paris, Esra Durmaz Mitchell, Envel Kerdaffrec, Thomas Flatt, Marisa A Rodrigues, Evolution Letters (2024) | Journal article -
Research projects
The Role of Adaptive Inversion Polymorphisms in their Ancestral Range
Status: OngoingStart 01.03.2024 End 29.02.2028 Funding SNSF Open project sheet Chromosome inversions have fascinated evolutionary biologists since the dawn of population genetics. Because they suppress single crossovers in heterozygous state, they can capture combinations of adaptive loci and protect them from recombination. Indeed, since their discovery in 1917, many adaptive, often stably polymorphic inversions have been found. Yet, despite a century of work, we do not conclusively understand their adaptive nature: What types of balancing selection act on inversions? What adaptive loci do they contain? What fitness traits do they affect? What selection pressures shape them? A classical model for studying inversions is Drosophila melanogaster. Most of this species’ inversions arose in Africa; after it migrated out of Africa and colonized the rest of the world, several became involved in climatic adaptation on other continents. However, little is known about these balanced cosmopolitan polymorphisms in their ancestral range, including whether they confer adaptation to wilderness habitats. Here, we seek to fill this major gap. By using a large panel of strains from southern-central Africa, we will study the role of these globally balanced polymorphisms in their ancestral range, thereby addressing fundamental questions about the nature of balancing selection. (1) Do cosmopolitan inversions represent long-term balanced polymorphisms? Did they capture adaptive loci before migrating out of Africa? What loci confer balancing selection upon inversions? Aim 1 will analyze phased sequencing data for four globally common inversions to identify footprints of balancing selection associated with these polymorphisms in ancestral populations. (2) Do inversions from ancestral habitats affect fitness traits? If yes, do such effects give us clues about selection pressures on inversions in ancestral habitats? Aim 2 will identify karyotype-phenotype associations by isolating karyotypes from a seasonally dry wilderness habitat in Zambia and measuring fitness-related stress response traits. (3) Are inversions from ancestral habitats subject to fluctuating balancing selection? We conjecture that inversions adaptively track wet-dry season fluctuations in temperature, precipitation, and food abundance in wilderness habitats. Aim 3 will survey seasonal fluctuations of inversion frequencies in samples from seasonally dry woodlands in Zambia and a tropical savannah climate in Nigeria. Secondly, we will use population cage assays to study the temporal dynamics of inversion frequencies in response to (i) seasonal changes in outdoor cages in a field facility subject to a humid subtropical climate that is similar to that of some ancestral habitats and (ii) controlled fluctuating conditions in laboratory population cages. Together, these approaches promise to yield novel insights into the adaptive nature of balanced polymorphisms and the mechanisms of fluctuating selection, a classical but largely unresolved question in evolutionary genetics. Entlastungsbeitrag
Status: CompletedSpiel des Lebens / Le jeu de la vie
Status: CompletedStart 01.02.2022 End 31.01.2023 Funding SNSF Open project sheet Questions about aging, longevity and immortality (the “fountain of youth”) have fascinated mankind since the dawn of time. Why do some people live much longer than others? Could we perhaps manage to stop aging and become immortal? These seemingly philosophical questions are firmly rooted in current research on aging and longevity. What is less well understood among non-biologists is why aging exists in the first place and how remarkably diverse patterns of lifespan and mortality are among organisms other than humans. The tremendous diversity of different patterns of aging and lifespan among bacteria, plants and animals holds great promise for answering deep questions such as: Are there organisms that truly do not age? If so, how do they manage to live so long and defeat aging? Is there a prize that organisms pay if they are exceptionally long-lived? To engage the public with these fundamental questions about life and death, the Natural History Museum of Fribourg will be organizing an exhibition that seeks to unite different perspectives (e.g., biological, philosophical, literary). The main exhibition is financed by the Museum itself. With this proposal we would like to add a subproject in collaboration with writers to dive into the topic in a new way. Regional authors will write fictional stories (based on biological facts) to be shown in the exhibition. Additionally, these authors will discuss their views on aging and life expectancy with scientists and offer writing courses for children and adults to write their own short stories about the exhibition’s topic. The best stories will make it into the exhibition. In this way, the subproject complements and extends the museum exhibition and will also reach audiences that are usually difficult to reach by traditional natural history museum exhibitions. The Role of Chromosomal Inversions in Clinal Adaptation
Status: CompletedStart 01.03.2019 End 30.09.2023 Funding SNSF Open project sheet Chromosomal inversions are well known to suppress recombination. This fact, and the observation that many inversions form predictable clines, prompted Theodosius Dobzhansky in the 1940s to postulate that they represent „coadapted gene complexes“, epistatic combinations of linked adaptive loci. An alternative hypothesis posits that inversions evolve because they capture locally adapted alleles and protect them from maladaptive gene flow from other populations. However, although inversions are often considered to play a significant role in adaptation, the genic targets of selection carried by them or how they are selectively maintained is poorly understood. With very few exceptions, phased genomic data required to identify candidate targets of selection within inversions are not yet available, and how inversions affect fitness traits is largely unknown. Here we propose to address these fundamental issues using the fruit fly Drosophila melanogaster as a powerful experimental test bed, by applying population genomics, laboratory and field assays, and experimental genetics approaches to a cosmopolitan, clinally varying inversion polymorphism, In(3R)Payne. Although we have previously shown that this polymorphism is maintained by selection across latitudinal gradients, how selection does so remains unclear; yet, precisely because of its adaptive nature, this chromosomal rearrangement represents an ideal model system for studying the selective mechanisms that act on inversions. Aim 1 will identify candidate targets of selection inside this inversion by using phased whole-genome sequencing data from inverted and uninverted karyotypes, which are to be functionally tested in Aim 4. The data from Aim 1 will also be used to test a key requirement for the selective advantage of an adaptive inversion, namely the existence of linkage disequilibrium among the putative loci subject to selection, and to identify candidate haplotypes under selection. Aim 2 will determine the phenotypic effects of this inversion upon fitness components by systematic phenotyping of homo- and heterokaryons under different thermal conditions in the laboratory; these assays will also test whether the polymorphism might be maintained by fitness overdominance. Aim 3 will use laboratory and field experiments to examine whether the inversion is maintained by frequency-dependent selection. Aim 4 will map the genetic basis of variation in fitness-related traits associated with the inversion by employing CRISPR/Cas9 genome editing. Together, these synergistic approaches promise the most in-depth analysis of the adaptive role of any inversion system to date. By unraveling the mechanisms whereby an inversion polymorphism affects fitness, our research program will illuminate a longstanding but still unresolved problem in evolutionary biology. The Genomic Basis of Life History Adaptation
Status: CompletedStart 01.12.2016 End 31.05.2019 Funding SNSF Open project sheet Life history traits are central to our understanding of adaptation because they represent direct targets of selection. However, while much progress has been made in uncovering the molecular mechanisms underlying fitness-related traits, mainly by studying large-effect mutants in model organisms, little is known about naturally occurring genetic variants that affect these traits. The central aim of my current SNSF Professorship grant is to identify naturally occurring polymorphisms that underlie evolutionary changes in life history, using Drosophila melanogaster as a model. Over the last 33 months, we have used two complementary approaches to tackle this problem: to generate "catalogs" of candidate variants we have applied whole-genome Pool-sequencing to (1) North American populations clinally differentiated for life history and (2) a >30-year-long artificial selection experiment for longevity. Both approaches are "designed" to maximize among-population life-history differentiation and thus to increase our ability to map life-history variants via sequencing. In a second step, we have begun to perform experiments to examine the life-history effects of some of these candidate mechanisms. Based on our genomic analyses, we have prioritized three candidate mechanisms for experiments: (1) for the cline, we have identified clinal SNP polymorphisms in several genes involved in insulin signaling, a pathway known from molecular studies to regulate life-history physiology, including a clinal 2-SNP polymorphism in the transcription factor gene foxo; (2) a clinal chromosomal inversion polymorphism, In(3R)Payne, to which 79% of the most strongly clinal SNPs in the genome map; and (3), in the selection experiment, we have found strong enrichment of immunity genes among our top candidates. To date, our experiments show that (1) the foxo polymorphism has major pleiotropic on egg-to-adult survival, body size and starvation resistance, in assays based on synthetic recombinant inbred lines; (2) the In(3R)Payne polymorphism is maintained by clinal selection, independent of neutrality and admixture, and affects body size, a strongly clinal trait; and (3) the long-lived selection lines survive pathogenic infections much better than the controls. In this application for a 2-year extension of my grant, we propose to follow up on these promising leads. First, to better understand how the foxo polymorphism affects life history, we will use homologous replacement of the 2 SNPs (and their allelic combinations) into a common background via CRISPR/Cas9, in collaboration with Alistair McGregor (Oxford); we will measure additive and epistatic effects of these constructs on life history and FOXO activity. Second, to identify targets of selection within In(3R)Payne, we will phase-sequence isochromosomal lines and apply ABC-based coalescent models to the data, in collaboration with Mark Kirkpatrick (Austin). In addition, we will perform RNA-seq of standard vs. inverted lines to uncover transcriptional differences between inversion karyotypes. Finally, to begin to uncover the regulatory details of the intriguing but poorly understood connection between lifespan and immunity in the longevity selection lines, we will assay transcriptional responses to infection in selection versus control lines, both in young and old flies, and – secondly – test whether silencing immune genes via transgenic RNAi affects lifespan, as hypothesized. Together, this integrative approach – spanning population genomics, functional genetics, and physiology – will significantly advance our understanding of the molecular basis of adaptive changes in life history and aging, a fundamental but largely unresolved problem in evolutionary biology. Physiological basis of the fecundity/longevity trade-off in Drosophila
Status: CompletedStart 01.01.2016 End 30.06.2019 Funding SNSF Open project sheet In many organisms curtailed reproduction increases lifespan. Conversely, extended lifespan is often accompanied by reduced reproduction. The overarching aim of our Research Unit (RU) is to investigate the evolution and mechanisms of the fecundity/ longevity trade-off in insects by comparing experimental manipulations in social insects, where – remarkably – the fecundity/longevity trade-off is typically absent, with data from solitary insects (e.g., Drosophila), where this trade-off is common and well-established. As a model for understanding the mechanisms underlying the fecundity/ longevity trade-off, we are planning to perform experiments in the fruit fly (Drosophila melanogaster), which shall serve as “solitary insect” reference system or “control” for the work to be done in social insects in our RU. The fact that decreased food intake without malnourishment (dietary restriction) extends lifespan while concomitantly reducing reproduction suggests that the longevity-reproduction trade-off might represent an energetic resource allocation trade-off. If so, food limitation might divert resources away from reproduction and make them available for somatic maintenance and survival. However, the trade-off in energy allocation between fecundity and metabolic storage is not quantitatively exact, and dietary restriction can increase lifespan in gonadectomized worms (Caenorhabditis elegans) and sterile flies (D. melanogaster), findings which are at odds with the resource allocation model. In contrast to C. elegans that lack the entire gonad, worms that lack germ cells only are long-lived, and dietary restriction cannot further extend longevity in these individuals, suggesting that signals from the germline may oppose those of the somatic gonad to regulate ageing in the worm. Therefore, although current knowledge indicates that nutrient metabolism, reproduction and ageing represent interconnected regulatory axes, the actual mechanisms underlying the trade-off between reproduction and longevity remain largely unknown. The main goal of the research proposed here to use the genetically powerful fruit fly model Drosophila melanogaster to test whether the reproductive and nutritional regulatory axes converge onto the same mechanisms that affect ageing. Specifically, we will use a sterile mutant with oogenic arrest and a germline-less, long-lived transgenic strain as experimentals tool to discover how reproduction interacts with diet to affect lifespan and physiology. To systematically characterize the global physiology underlying the fecundity/longevity trade-off in Drosophila we will combine transcriptomics, metabolomics, endocrine assays, and RNAi silencing of candidate genes. The effects of germline stem cells on aging and reproduction in Drosophila melanogaster
Status: CompletedStart 01.04.2004 End 31.03.2005 Funding SNSF Open project sheet The effects of germline stem cells on aging and reproduction in Drosophila melanogaster Pleiotropic effects of juvenile hormone metabolism on Drosophila life history
Status: CompletedThe effects of juvenile hormone on trait architecture in Drosophila melanogaster
Status: CompletedConsequences of source-sink population dynamics for adaptive evolution in marginal habitats: theoretical and experimental approaches
Status: Completed