| | | Programme |
The evolution of mechanisms: a workshop on the integration of life-history evolution and physiology 28-31 January, 2016, University of Debrecen, Debrecen, Hungary
Schedule
28-31 January, 2016. University of Debrecen
28 Jan (Thursday): Arrival, registration, welcome reception
29-30 Jan (Friday-Saturday): invited and contributed talks and discussions
31 Jan (Sunday): social event: wine tasting tour (details below)
Invited speakers
David Gems (UCL) Ageing in C. elegans: linking mechanistic and evolutionary theories
Arguably, biogerontology has stalled a bit during the last years. Life span genetics identifies ever more new genes and pathways, yet the fundamental mechanisms of ageing remain largely unclear. The damage-maintenance paradigm that has guided so many studies of ageing mechanisms seems increasingly inadequate – but surely there is some truth in it? And the question of how to link evolutionary theories about ageing – particularly antagonistic pleiotropy – with actual biological mechanisms remains very much an open one. Recent work in my lab has used ideas from M.V. Blagosklonny to develop and test hypotheses about the primary causes of ageing in C. elegans. These ideas link G.C. Williams’ evolutionary ideas with recent findings on the role of insulin/IGF-1 signaling in ageing, providing a new proximate-ultimate integrated theory. This has facilitated the discovery of a number of new mechanisms by which ageing-related pathologies originate from wild type gene function in C. elegans, and suggest a new theory about the relationship between damage and antagonistic pleiotropy in the etiology of senescence.
Thomas Flatt (Department of Ecology and Evolution, University of Lausanne) The Mechanisms Underpinning Life History Evolution
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 and transgenes in model organisms, very little is known about naturally occurring genetic variants that affect these traits. Here I will discuss the problem of how to identify and study such life-history polymorphisms, by using latitudinal clines in the fruit fly (Drosophila melanogaster) as an example. In this species, many fitness-related traits (including body size, fecundity, lifespan, stress resistance, and reproductive diapause) exhibit clinal gradients, often on multiple continents. By applying next-generation sequencing and population genomics to populations along the North American east coast, we have identified numerous clinally varying variants, many of which reside in genes and pathways known from molecular genetic analyses to affect life history physiology. Some of the most promising clinal candidates are alleles in genes of the insulin/insulin-like growth factor signaling (IIS) pathway. For example, we have identified a clinal 2-SNP polymorphism in the forkhead box O transcription factor gene foxo (called daf-16 in C. elegans), a central component of IIS known to affect growth, lifespan and stress resistance. Using an approach based on synthetic recombinant inbred populations, we find that this naturally occurring foxo polymorphism has major pleiotropic effects on egg-to-adult survival, body size and starvation resistance. Although foxo is known to affect these traits in studies of laboratory mutants and transgenes, our results provide the first demonstration that naturally occurring alleles at this locus can have similar effects. Another very interesting outcome of our genomic analyses is that the majority of all clinal candidates is located within a specific genomic region spanned by a large, cosmopolitan and strongly clinal chromosomal inversion, In(3R)Payne (depending on the analysis approx. 50-79% of SNPs). Interestingly, this inversion harbors numerous genes known to be involved in life history physiology, including several major IIS genes. Our results suggest that this inversion polymorphism is indeed maintained by spatially varying selection across the cline, independent of neutrality and admixture, and that it affects various size-related traits which are themselves known to show a clinal distribution. I argue that employing the kind of integrative approache exemplified here – spanning population genomics, functional genetics, and physiology – can 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.
Further Reading
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.
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
Flatt, T., Amdam, G.V., Kirkwood, T.B.L., and S. W. Omholt. 2013. Life-history evolution and the polyphenic regulation of somatic maintenance and survival. Quarterly Review of Biology 88: 185-218.
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.
Flatt, T., and A. Heyland (Editors). 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., and P.S. Schmidt. 2009. Integrating evolutionary and molecular genetics of aging. Biochimica et Biophysica Acta 1790:951-962.
Laura Lavine (Washington State University) Endocrine signaling and the development of the weapons of sexual selection: insights from beetles
Insects exhibit an amazing diversity of sexually-selected, environmentally sensitive phenotypes. For example, mandible size in male stag beetles is exquisitely sensitive to the larval nutritional environment and is a reliable signal of male condition, critical to male mating success. To date, studies of how such traits develop have focused on two types of mechanistic processes. Local, tissue-specific genetic mechanisms specify the shape and approximate final size of structures, whereas whole-animal hormonal signaling mechanisms modulate trait growth in response to environmental circumstance, including the body size and nutritional state of each individual. Hormones such as juvenile hormone, ecdysteroids, and/or ligands of the insulin-signaling pathway specify whether traits grow and regulate how much growth occurs across a diversity of insect groups. Interestingly, hormonal signaling is well known to modulate sexually-selected traits across the animal kingdom. I will discuss these processes and their evolution in the sexually-selected traits of animals.
Pat Monaghan (Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow) Environmental effects that shape individual life histories: mechanisms, trade-offs and time scales
In this talk I will discuss how environmental factors experienced in early life can result in phenotypic adjustments that have long term consequences, and generate trade-off operating over long time scales. I will present recent data from a range of fish and bird species, involving observations and experiments in the field and in the lab on how the pattern of growth, stress exposure and other early life factors influence phenotypic development and can affect later life reproduction and longevity. I will also discuss how the environment in adult life can interact with that in early life to influence outcomes. We have investigated a number of number of mechanistic process that might underlie these long lasting effects including changes in stress sensitivity, telomere dynamics and exposure to oxidative stress.
Social event
We will organize an optional wine tasting tour in Tállya, situated in the heart of the famous Tokaj wine region. We will visit several hundred years old wine cellars and will taste a wide array of spectacular wines, taken directly from the barrels. The price is not included in the registration fee. Details will be posted soon.
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