Thomas Flatt
Professor
PER 23 - 1.01
+41 26 300 8833
E-mail
The Genomic Basis of Adaptation
We are interested in the population genetics and evolutionary genomics of adaptation, mainly by using the fruit fly Drosophila melanogaster as an experimentally tractable model. The components of fitness, so-called life-history traits (e.g., growth, size, fecundity, survival, lifespan), are complex polygenic traits that are fundamentally important for adaptation because they represent the targets of selection at the phenotypic level. However, still little is known about the genetic basis of variation and evolutionary changes in such fitness-related traits. Similarly, the mechanisms that maintain the large amounts of genetic variation in fitness components in natural populations remain incompletely understood.
The questions we ask in our research group include:
- What are the loci underlying life-history adaptations?
- What is the genomic basis of local adaptation along clines?
- How do inversions and supergenes shape adaptation?
- How does balancing selection maintain life-history polymorphisms?
- How does lifespan evolve? What are the costs of longevity?
- Why does reproduction shorten lifespan?
We study these questions, e.g., in the context of climate adaptation and life-history clines across latitudinal gradients, chromosomal inversion polymorphisms maintained by spatially varying selection and other forms of balancing selection, and the evolution of aging and trade-offs associated with longevity and other fitness traits.
To address these longstanding problems we combine population genetics and population genomics, functional genetics, transcriptomics, physiology, and experimental evolution and apply them to natural and laboratory populations of D. melanogaster that are phenotypically differentiated for fitness-related traits. Occasionally, we are also involved in collaborative studies on other organisms. While most of our work is empirical and experimental, it is strongly conceptually motivated; our review papers synthesize key problems and set directions for future research. Sometimes we also collaborate with theoreticians.
Part of our work is in collaboration with the European Drosophila Population Genomics Consortium (DrosEU) and the Drosophila Real-Time Evolution Consortium (Dros-RTEC); for our recent consortium papers see Kapun et al. (2020 and 2021) in Molecular Biology and Evolution (pdf1) (pdf2) and Machado et al. (2021) in eLife (pdf). A recent output of our DrosEU-DrosRTEC collaboration is a data repository and genome browser called DEST (Drosophila Evolution over Space and Time), encompassing genome-wide allele frequency estimates from >270 population samples of D. melanogaster, based on sequencing of >13,000 flies collected world-wide and over multiple years (DEST page).
See Flatt (2020) in Genetics () for a comprehensive review of the kind of research questions we are interested in.
-
What loci underlie life-history evolution?
"...integrating an understanding of mechanisms into life history theory will be one of the most exciting tasks facing evolutionary biologists in the 21st century."
(Barnes & Partridge 2003, in Animal Behaviour)
We have a major interest in identifying the genes and molecular polymorphisms that underpin variation in fitness components (so-called life-history traits), such as body size, reproduction and lifespan, and in determining how they contribute to adaptation. The identification of such life-history polymorphisms allows addressing fundamental questions about the genetic basis of adaptation, including:
- Which pathways underpin life-history variation?
- Are these mechanisms evolutionarily conserved?
- What are the effects of life-history polymorphisms?
- What is the molecular basis of life-history pleiotropy?
- To what extent is life-history evolution ‘predictable’?
We have been studying these questions mainly in the context of (1) life-history clines, i.e. natural populations of fruit flies that are clinally (latitudinally) differentiated for major life history traits (e.g., size, fecundity, lifespan, stress resistance, and reproductive dormancy) and (2) the experimental evolution of aging and longevity. Our main approach has been to use population genomics to identify candidate loci and polymorphisms and then to study and validate these candidates experimentally. These studies have led us to explore the role of natural variation in the insulin/insulin-like growth factor signaling (IIS) pathway and of chromosomal inversion polymorphisms in affecting fitness components. In a similar vein, we have studied the role of immunity genes in affecting lifespan.
For a compehensive review of the evolutionary genetics of fitness components see
Some of our work on life-history clines
Kapun, M.*, Durmaz Mitchell, E., Kawecki, T.J., Schmidt, P., and T. Flatt.* 2023. An Ancestral Balanced Inversion Polymorphism Confers Global Adaptation. [*co-corresponding authors]. Molecular Biology and Evolution 40(6):msad118.
Betancourt, N., Rajpurohit, S., Durmaz, E., Fabian, D.K., Kapun, M., Flatt, T.*, and P. Schmidt*. 2021. Allelic polymorphism at foxo contributes to local adaptation in Drosophila melanogaster [*co-corresponding]. Molecular Ecology 30:2817-2830.
Kapun, M.*, Barrón, M.G., Staubach, F., Vieira, J., Obbard, D.J., Wiberg, R. A. W., Goubert, C., Rota-Stabelli, O., Kankare, M., Haudry, A., Waidele, L., Kozeretska, I., Pasyukova, E.G., Loeschcke, V., Pascual, M., Vieira, C.P., Serga, S., Montchamp-Moreau, C., Abbott, J., Gibert, P., Porcelli, D., Posnien, N., Grath, S., Sucena, E., Bergland, A.O., Garcia Guerreiro, M.P., Onder, B.S., Argyridou, E., Guio, L., Schou, M.F., Deplancke, B., Vieira, C., Ritchie, M.G., Zwaan, B.J., Tauber, E., Orengo, D.J., Puerma, E., Aguadé, M., Schmidt, P.S., Parsch, J., Betancourt, A.J., Flatt, T.*, and J. González*. 2020. Genomic analysis of European Drosophila melanogaster populations reveals longitudinal structure, continent-wide selection, and unknown DNA viruses. [*co-corresponding]. Molecular Biology and Evolution 37:2661-2678.
Durmaz, E., Rajpurohit, S., Betancourt, N., Fabian, D.K., Kapun, M., Schmidt, P., and T. Flatt. 2019. A clinal polymorphism in the insulin signaling transcription factor foxo contributes to life-history adaptation in Drosophila. Evolution 73:1774-1792.
Kapun, M., and T. Flatt. 2019. The adaptive significance of chromosomal inversion polymorphisms in Drosophila melanogaster. Molecular Ecology 28:1263-1282.
Durmaz, E., Benson, C., Kapun, M., Schmidt, P., and T. Flatt. 2018. An Inversion Supergene in Drosophila Underpins Latitudinal Clines in Survival Traits. Journal of Evolutionary Biology 31:1354-1364.
Kapun, M., Schmidt, C., Durmaz, E., Schmidt, P.S., and T. Flatt. 2016. Parallel effects of the inversion In(3R)Payne on body size across the North American and Australian clines in Drosophila melanogaster. Journal of Evolutionary Biology 29:1059-1072.
Kapun, M., Fabian, D.K., Goudet, J., and T. Flatt. 2016. Genomic Evidence for Adaptive Inversion Clines in Drosophila melanogaster. Molecular Biology and Evolution 33:1317-1336.
Fabian, D. K., Lack, J. B., Mathur, V., Schlötterer, C., Schmidt, P.S., Pool, J.E, and T. Flatt. 2015. Spatially varying selection shapes life history clines among populations of Drosophila melanogaster from sub-Saharan Africa. Journal of Evolutionary Biology 28:826-840.
Klepsatel, P., Galikova, M, Huber, C.D., and T. Flatt. 2014. Similarities and differences in altitudinal versus latitudinal variation for morphological traits in Drosophila melanogaster. Evolution 68:1385-1398.
Fabian, D.K., Kapun, M., Nolte, V., Kofler, R., Schmidt, P.S., Schlötterer, C. and T. Flatt. 2012. Genome-wide patterns of latitudinal differentiation among populations of Drosophila melanogaster from North America. Molecular Ecology 21:4748–4769.
Some of our work on aging and longevity
Rodrigues, M.A., Dauphin-Villemant, C., Paris, M., Kapun, M., Durmaz Mitchell, E., Kerdaffrec, E., and T. Flatt. 2024. Germline proliferation trades off with lipid metabolism in Drosophila. Evolution Letters 8: 295-310
Hoedjes, K.M., Kostic, H., Flatt, T., and L. Keller. 2023. A single nucleotide variant in the PPARgamma-homolog Eip75B affects fecundity in Drosophila. Molecular Biology and Evolution 40(2):msad018.
Hoedjes, K. M., Kostic, H., Keller, L., and T. Flatt. 2022. Natural alleles at the Doa locus underpin evolutionary changes in Drosophila lifespan and fecundity. Proceedings of the Royal Society of London B 289:20221989.
Harrison, M.C., Jaimes, L.M., Rodrigues, M.A., Flatt, T., Oettler, J., and E. Bornberg-Bauer. 2021. Gene co-expression network reveals highly conserved, well-regulated anti-ageing mechanisms in old ant queens. Genome Biology and Evolution 13(6).
Korb, J., Meusemann, K., Aumer, D., Bernadou, A., Elsner, D., Feldmeyer, B., Foitzik, S., Heinze, J., Libbrecht, R., Lin, S., Majoe, M., Monroy Kuhn J.M., Nehring, V., Negroni, M., Paxton, R., Séguret, A., Stoldt, M., and T. Flatt. 2021. Comparative transcriptomic analysis of the mechanisms underpinning ageing and fecundity in social insects. Philosophical Transactions of the Royal Society of London B 376 (1823):20190728.
Hoedjes, K., van den Heuvel, J., Kapun, M., Keller, L., Flatt, T., and B.J. Zwaan. 2019. Distinct Genomic Signals of Lifespan and Life History Evolution in Response to Postponed Reproduction and Larval Diet in Drosophila. Evolution Letters 3:598-609.
Fabian, D.K., Garschall, K., Klepsatel, P., Santos-Matos, G., Sucena, E., Kapun, M., Lemaitre, B., Schlötterer, C., Arking, R., and T. Flatt. 2018. Evolution of longevity improves immunity in Drosophila. Evolution Letters 2(6):567-579.
Flatt, T., and L. Partridge. 2018. Horizons in the Evolution of Aging. BMC Biology 16(1):93.
Garschall, K., Dellago, H., Gáliková, M., Schosserer, M., Flatt, T., and J. Grillari. 2017. Ubiquitous overexpression of the DNA repair factor dPrp19 reduces DNA damage and extends Drosophila life span. npj Aging and Mechanisms of Disease 3:5.
Flatt, T., and P.S. Schmidt. 2009. Integrating evolutionary and molecular genetics of aging. Biochimica et Biophysica Acta 1790:951-962.
Flatt, T., Min, K.-J., D’Alterio, C., Villa-Cuesta, E., Cumbers, J., Lehmann, R., Jones, D.L., and M. Tatar. 2008. Drosophila germ-line modulation of insulin signaling and lifespan. Proceedings of the National Academy of Sciences USA 105:6368-6373.
Flatt, T., and D.E.L. Promislow. 2007. Physiology: still pondering an age-old question. Science 318:1255-1256.
Flatt, T., and T.J. Kawecki. 2007. Juvenile hormone as a regulator of the trade-off between reproduction and life span in Drosophila melanogaster. Evolution 61:1980-1991.
Flatt, T. 2004. Assessing natural variation in genes affecting Drosophila lifespan. Mechanisms of Ageing and Development 125:155-159.
-
How do inversions affect adaptation?
"Legend has it that, when asked why he robbed banks, Willie Sutton replied, “Because that’s where the money is”... This impeccable logic is equally useful to guide the hunt for genes that are evolving adaptively. Starting with Dobzhansky’s pioneering work, dozens of polymorphic chromosome inversions have been found that show signatures of strong selection... But despite decades of research on inversions, we still know little about which of the genes they carry are the targets of selection or how the polymorphisms themselves are maintained."
(Kirkpatrick & Kern 2012, in Genetics)
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 (also called supergenes). 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.
In this project we aim to address these fundamental issues using D. 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 and that it affects several fitness-related traits, 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, for example the potential role of associative overdominance, pseudo-overdominance and/or frequency-dependent selection. We are also interested in identifying the causative loci spanned by In(3R)Payne and their effects upon fitness components.
For a comprehensive review of the adaptive significance of inversion polymorphisms in D. melanogaster see Kapun & Flatt (2019) in Molecular Ecology (pdf).
Some of our work on adaptive inversions
Berdan, E.L.*, Barton, N.H., Butlin, R., Charlesworth, B., Faria, R., Fragata, I., Gilbert, K.J., Jay, P., Kapun, M., Lotterhos, K.E., Mérot, C., Durmaz Mitchell, E., Pascual, M., Peichel, C.L., Rafajlović, M., Westram, A.M., Schaeffer, S.W.*, Johannesson, K.*, and T. Flatt.* 2023. How chromosomal inversions reorient the evolutionary process. [*co-corresponding authors]. Journal of Evolutionary Biology 36:1761-1782.
Kapun, M.*, Durmaz Mitchell, E., Kawecki, T.J., Schmidt, P., and T. Flatt.* 2023. An Ancestral Balanced Inversion Polymorphism Confers Global Adaptation. [*co-corresponding authors]. Molecular Biology and Evolution 40(6):msad118.
Berdan, E. L., Blanckaert, A., Butlin, R., Flatt, T., Slotte, T., and B. Wielstra. 2022. Mutation accumulation opposes polymorphism: Supergenes and the curious case of balanced lethals. Philosophical Transactions of the Royal Society of London B 377:20210199.
Berdan, E. L., Flatt, T., Kozak, G. M., Lotterhos, K. E., and B. Wielstra. 2022. Genomic architecture of supergenes: Connecting form and function. Philosophical Transactions of the Royal Society of London B 377:20210192.
Machado, H.E., Bergland, A.O., Taylor, R., Tilk, S., Behrman, E., Dyer, K., Fabian, D.K., Flatt, T., Gonzàlez, J., Karasov, T.L., Kim, B., Kozeretska, I., Lazzaro, B. P., Merritt, T.J.S., Pool, J.E., O'Brien, K.O., Rajpurohit, S., Roy, P.R., Schaeffer, S.W., Serga, S., Schmidt, P., and D. A. Petrov. 2021. Broad geographic sampling reveals the shared basis and environmental correlates of seasonal adaptation in Drosophila. eLife 2021; 10:e67577.
Charlesworth, B., & Flatt, T. 2021. On the Fixation or Non-Fixation of Inversions Under Epistatic Selection. Molecular Ecology 30:3896-3897.
Durmaz, E., Kerdaffrec, E., Katsianis, G., Kapun, M.*, and T. Flatt*. 2020. How Selection Acts on Chromosomal Inversions. [*co-corresponding]. eLS (Encyclopedia of Life Sciences) 1:307-315, 2020.
Kapun, M.*, Barrón, M.G., Staubach, F., Vieira, J., Obbard, D.J., Wiberg, R. A. W., Goubert, C., Rota-Stabelli, O., Kankare, M., Haudry, A., Waidele, L., Kozeretska, I., Pasyukova, E.G., Loeschcke, V., Pascual, M., Vieira, C.P., Serga, S., Montchamp-Moreau, C., Abbott, J., Gibert, P., Porcelli, D., Posnien, N., Grath, S., Sucena, E., Bergland, A.O., Garcia Guerreiro, M.P., Onder, B.S., Argyridou, E., Guio, L., Schou, M.F., Deplancke, B., Vieira, C., Ritchie, M.G., Zwaan, B.J., Tauber, E., Orengo, D.J., Puerma, E., Aguadé, M., Schmidt, P.S., Parsch, J., Betancourt, A.J., Flatt, T.*, and J. González*. 2020. Genomic analysis of European Drosophila melanogaster populations reveals longitudinal structure, continent-wide selection, and unknown DNA viruses. [*co-corresponding]. Molecular Biology and Evolution 37:2661-2678.
Kapun, M., and T. Flatt. 2018. The adaptive significance of chromosomal inversion polymorphisms in Drosophila melanogaster. Molecular Ecology 28:1263-1282
Durmaz, E., Benson, C., Kapun, M., Schmidt, P., and T. Flatt. 2018. An Inversion Supergene in Drosophila Underpins Latitudinal Clines in Survival Traits. Journal of Evolutionary Biology 31: 1354-1364.
Kapun, M., Schmidt, C., Durmaz, E., Schmidt, P.S., and T. Flatt. 2016. Parallel effects of the inversion In(3R)Payne on body size across the North American and Australian clines in Drosophila melanogaster. Journal of Evolutionary Biology 29:1059-1072.
Kapun, M., Fabian, D.K., Goudet, J., and T. Flatt. 2016. Genomic Evidence for Adaptive Inversion Clines in Drosophila melanogaster. Molecular Biology and Evolution 33:1317-1336.
Flatt, T. 2016. Genomics of clinal variation in Drosophila: disentangling the interactions of selection and demography. Molecular Ecology 25:1023-1026.
Kapun, M., van Schalwyk, H., McAllister, B., Flatt, T., and C. Schlötterer. 2014. Inference of chromosomal inversion dynamics from Pool-Seq data in natural and laboratory populations of D. melanogaster. Molecular Ecology 23:1813-1827.
Fabian, D.K., Kapun, M., Nolte, V., Kofler, R., Schmidt, P.S., Schlötterer, C. and T. Flatt. 2012. Genome-wide patterns of latitudinal differentiation among populations of Drosophila melanogaster from North America. Molecular Ecology 21:4748–4769.
-
How do trade-offs work mechanistically?
“It would be instructive to know not only by what physiological mechanisms a just apportionment is made between the nutriment devoted to the gonads and that devoted to the rest of the parental organism, but also what circumstances in the life-history and environment would render profitable the diversion of a greater or lesser share of the available resources towards reproduction.”
R. A. Fisher (1930), The Genetical Theory of Natural Selection
Trade-offs, for example between fecundity and lifespan (so-called costs of reproduction) are ubiquitous, but still very little is known about their underlying genetic and physiological mechanisms. The most commonly held view is that such trade-offs at the organismal level result from underlying resource allocation (metabolic, energetic) trade-offs. A not mutually exclusive possibility is that such trade-offs are due to other pleiotropic constraints, including molecular signals, that are independent of resource allocation. Interestingly, work in the nematode worm C. elegans indicates that reproduction and lifespan might be linked by signals produced by reproductive tissues. In this species lifespan is extended if worms lack proliferating germ cells in the presence of an intact somatic gonad. The gonad might thus be the source of signals which physiologically modulate organismal aging.
In previous work we have shown that such gonadal signals are also present in D. melanogaster, suggesting that the regulation of lifespan by the reproductive system is evolutionarily conserved. Ablation of germline stem cells in the fly extends lifespan, modulates insulin signaling in peripheral tissues, and alters carbohydrate and fat metabolism. Thus, as of yet unidentified endocrine signals from the germline might converge onto insulin signaling to regulate aging and adult physiology.
Our current work focuses on identifying the transcriptomic and hormonal mechanisms that underlie the physiological regulation of the trade-off between reproduction and somatic maintenance in the fly (e.g., survival, lifespan, stress resistance, immunity). Most recently, we have studied how reproduction (germline ablation vs. normal fertility) affects the innate immune system. Our findings suggest that germline activity impedes the expression and inducibility of immune genes and that this physiological trade-off might be evolutionarily conserved.
In an international consortium with colleagues who study social insects (So-Long project), we have also begun to explore potential mechanisms that might explain how queens in social insects can 'defy' the commonly observed trade-off between fecundity and longevity (this consortium effort has recently been featured in a news story in Science).
For a comprehensive overview of genetical and physiological mechanisms that underpin life-history evolution and especially trade-offs see the edited volume by Flatt & Heyland (2011, Oxford University Press, link).
Some of our work on life-history trade-offs and pleiotropy
Rodrigues, M.A., Dauphin-Villemant, C., Paris, M., Kapun, M., Durmaz Mitchell, E., Kerdaffrec, E., and T. Flatt. 2024. Germline proliferation trades off with lipid metabolism in Drosophila. Evolution Letters 8: 295-310.
Rau, V., Flatt, T., & J. Korb. 2023. Remoulding of dietary effects on the fecundity / longevity trade-off in a social insect. BMC Genomics 24:244.
Hoedjes, K.M., Kostic, H., Flatt, T., and L. Keller. 2023. A single nucleotide variant in the PPARgamma-homolog Eip75B affects fecundity in Drosophila. Molecular Biology and Evolution 40(2):msad018.
Hoedjes, K. M., Kostic, H., Keller, L., and T. Flatt. 2022. Natural alleles at the Doa locus underpin evolutionary changes in Drosophila lifespan and fecundity. Proceedings of the Royal Society of London B 289:20221989.
Rodrigues, M.A., Merckelbach, A., Durmaz, E., Kerdaffrec, E., and T. Flatt. 2021. Transcriptomic Evidence for a Trade-off between Germline Proliferation and Immunity in Drosophila. Evolution Letters 5:644-656.
Korb, J., Meusemann, K., Aumer, D., Bernadou, A., Elsner, D., Feldmeyer, B., Foitzik, S., Heinze, J., Libbrecht, R., Lin, S., Majoe, M., Monroy Kuhn J.M., Nehring, V., Negroni, M., Paxton, R., Séguret, A., Stoldt, M., and T. Flatt. 2021. Comparative transcriptomic analysis of the mechanisms underpinning ageing and fecundity in social insects. Philosophical Transactions of the Royal Society of London B 376 (1823): 20190728.
Pen, I., and T. Flatt. 2021. Asymmetry, Division of Labour and the Evolution of Ageing in Multicellular Organisms. Philosophical Transactions of the Royal Society of London B 376 (1823): 20190729.
Rodrigues, M.A., and T. Flatt. 2016. Endocrine uncoupling of the trade-off between reproduction and somatic maintenance in eusocial insects. Current Opinion in Insect Science 16:1-8.
Hansen, M., Flatt, T., and H. Aguilaniu. 2013. Reproduction, Fat Metabolism, and Life Span: What Is the Connection? Cell Metabolism 17:10-19.
Flatt, T., and A. Heyland (Eds.). 2011. Mechanisms of Life History Evolution. The Genetics and Physiology of Life History Traits and Trade-Offs. Oxford University Press, Oxford, UK. 478 pages, 75 illustrations, ISBN 978-0-19-956877-2.
Flatt, T. 2011. Survival costs of reproduction in Drosophila. Experimental Gerontology 46:369-375.
Flatt, T., Min, K.-J., D’Alterio, C., Villa-Cuesta, E., Cumbers, J., Lehmann, R., Jones, D.L., and M. Tatar. 2008. Drosophila germ-line modulation of insulin signaling and lifespan. Proceedings of the National Academy of Sciences USA 105:6368-6373.
Flatt, T., and D.E.L. Promislow. 2007. Physiology: still pondering an age-old question. Science 318:1255-1256.
Flatt, T., and T.J. Kawecki. 2007. Juvenile hormone as a regulator of the trade-off between reproduction and life span in Drosophila melanogaster. Evolution 61:1980-1991.
Flatt, T., Tu, M.-P., and M. Tatar. 2005. Hormonal pleiotropy and the juvenile hormone regulation of Drosophila development and life history. BioEssays 27:999-1010.
Flatt, T., and T.J. Kawecki. 2004. Pleiotropic effects of Methoprene-tolerant (Met), a gene involved in juvenile hormone metabolism, on life history traits in Drosophila melanogaster. Genetica 122:141-160
-
How does aging evolve?
Between the 1930s and 1960s, evolutionary geneticists worked out the basic principles of why organisms age. Despite much progress in the evolutionary and molecular biology of ageing since that time, however, many puzzles remain. How does aging evolve, mechanistically? What genes and polymorphisms underlie natural variation in lifespan and evolutionary changes in patterns of aging? What are the molecular and physiological mechanisms underpinning longevity and trade-offs between lifespan and other fitness components?
We are trying to improve our understanding of these problems using a combination of experimental evolution, genetics, physiology, genomics and transcriptomics. In the past we have studied, e.g., the endocrine modulation of trade-offs between reproduction and lifespan (and somatic maintenance more generally); aspects of dietary restriction; the role of DNA damage repair factors in longevity; and the connection between the evolution of lifespan and the innate immune system. Also see our collaborative work on aging in social insects with the So-Long consortium (So-Long project).
More recently, in collaboration with Ido Pen (Groningen), we have also become interested in the fundamental question of which organisms are expected to age and which are not (or which should age rapidly and which should not), an issue that is closely related to the concept of 'division of labor' and hence trade-offs.
For a recent review that summarizes many of the puzzles we are interested in see Flatt & Partridge (2018) in BMC Biology (pdf).
Some of our work on aging and longevity
Rau, V., Flatt, T., & J. Korb. 2023. Remoulding of dietary effects on the fecundity / longevity trade-off in a social insect. BMC Genomics 24:244.
Hoedjes, K.M., Kostic, H., Flatt, T., and L. Keller. 2023. A single nucleotide variant in the PPARgamma-homolog Eip75B affects fecundity in Drosophila. Molecular Biology and Evolution 40(2):msad018.
Hoedjes, K. M., Kostic, H., Keller, L., and T. Flatt. 2022. Natural alleles at the Doa locus underpin evolutionary changes in Drosophila lifespan and fecundity. Proceedings of the Royal Society of London B 289:20221989.
Promislow, D.E.L., Flatt, T., and R. Bonduriansky. 2022. The Biology of Aging in Insects: From Drosophila to Other Insects and Back. Annual Review of Entomology 67:83–103.
Harrison, M.C., Jaimes, L.M., Rodrigues, M.A., Flatt, T., Oettler, J., and E. Bornberg-Bauer. 2021. Gene co-expression network reveals highly conserved, well-regulated anti-ageing mechanisms in old ant queens. Genome Biology and Evolution 13(6).
Korb, J., Meusemann, K., Aumer, D., Bernadou, A., Elsner, D., Feldmeyer, B., Foitzik, S., Heinze, J., Libbrecht, R., Lin, S., Majoe, M., Monroy Kuhn J.M., Nehring, V., Negroni, M., Paxton, R., Séguret, A., Stoldt, M., and T. Flatt. 2021. Comparative transcriptomic analysis of the mechanisms underpinning ageing and fecundity in social insects. Philosophical Transactions of the Royal Society of London B 376 (1823): 20190728.
Pen, I., and T. Flatt. 2021. Asymmetry, Division of Labour and the Evolution of Ageing in Multicellular Organisms. Philosophical Transactions of the Royal Society of London B 376 (1823): 20190729.
Hoedjes, K., van den Heuvel, J., Kapun, M., Keller, L., Flatt, T., and B.J. Zwaan. 2019. Distinct Genomic Signals of Lifespan and Life History Evolution in Response to Postponed Reproduction and Larval Diet in Drosophila. Evolution Letters 3:598-609.
May, T., van den Heuvel, J., Doroszuk, A., Hoedjes, K., Flatt, T., and B. J. Zwaan. 2019. Adaptation to developmental diet influences the response to selection on age at reproduction in the fruit fly. Journal of Evolutionary Biology 32:425-437.
Fabian, D.K., Garschall, K., Klepsatel, P., Santos-Matos, G., Sucena, E., Kapun, M., Lemaitre, B., Schlötterer, C., Arking, R., and T. Flatt. 2018. Evolution of longevity improves immunity in Drosophila. Evolution Letters 2(6):567-579.
Flatt, T., and L. Partridge. 2018. Horizons in the Evolution of Aging. BMC Biology 16(1):93.
Garschall, K., and T. Flatt. 2018. The interplay between immunity and aging in Drosophila. F1000Research 2018, 7(F1000 Faculty Rev):160.
Garschall, K., Dellago, H., Gáliková, M., Schosserer, M., Flatt, T., and J. Grillari. 2017. Ubiquitous overexpression of the DNA repair factor dPrp19 reduces DNA damage and extends Drosophila life span. npj Aging and Mechanisms of Disease 3:5.
Flatt, T., and P.S. Schmidt. 2009. Integrating evolutionary and molecular genetics of aging. Biochimica et Biophysica Acta 1790:951-962.
Flatt, T., Min, K.-J., D’Alterio, C., Villa-Cuesta, E., Cumbers, J., Lehmann, R., Jones, D.L., and M. Tatar. 2008. Drosophila germ-line modulation of insulin signaling and lifespan. Proceedings of the National Academy of Sciences USA 105:6368-6373.
Flatt, T., and D.E.L. Promislow. 2007. Physiology: still pondering an age-old question. Science 318:1255-1256.
Flatt, T., and T.J. Kawecki. 2007. Juvenile hormone as a regulator of the trade-off between reproduction and life span in Drosophila melanogaster. Evolution 61:1980-1991.
Flatt, T. 2004. Assessing natural variation in genes affecting Drosophila lifespan. Mechanisms of Ageing and Development 125:155-159.