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PhD Topics 2019

  • Complex trait dissection in conifers. Summary
  • Dissecting the genetic basis of co-selected traits during thermal adaptation in Drosophila simulans. Summary
  • Efficient detection of variants of polygenic adaptation in Drosophila experimental evolution. Summary
  • Evolution of gene expression. Summary
  • Functional characterization of beneficial alleles in Drosophila. Summary
  • Genomic architecture of reverse selection. Summary
  • Incipient speciation during adaptation to a new environment. Summary
  • Inference of selection parameters using whole genome data. Summary
  • Long-term dynamics of adaptive alleles. Summary
  • Microbiome evolution in Drosophila. Summary
  • Multi-measurement experimental evolution: How to combine evidence from different sources? Summary
  • Polygenic adaptation: The roles of pleiotropy and epistasis. Summary
  • The genetics of local adaptation in Arabidopsis thaliana. Summary
  • The role of a nascent sex chromosome on interspecific patterns of allele sharing. Summary
  • Transposon polymorphism in Arabidopsis thaliana. Summary
  • Within-species consequences of genomic interactions in ecologically important species. Summary

More topics


Complex trait dissection in conifers

Principal advisor: Kelly Swarts

Trees are critical components of forest ecosystems but their long generation times make it particularly challenging to adapt to rapidly changing climate. Long generation times also make traditional quantitative genetics approaches for isolating genetic and adaptive (genotype by environment) variation costly and time-intensive. This project focuses on developing a new approach to isolating adaptive variation in natural forest stands using tree-ring information, and then understanding the genetics underlying adaptive variation using genomic approaches. This project involves significant fieldwork sampling trees; a computational or statistical background would be helpful, but is not required.


Dissecting the genetic basis of co-selected traits during thermal adaptation in Drosophila simulans

Principal advisor: Neda Barghi, Christian Schlötterer

Both temperature mean and temperature fluctuations have important roles in thermal adaptation. Recent studies suggest that adaptation to mean temperature and fluctuation in temperature are distinct traits but their genetic basis and distinct effects of these selective pressures, i.e. constant and fluctuating temperature, on thermal adaptation are still largely unknown. This project aims to characterize genomic regions involved in thermal adaptation and to dissect the genes responsible for adaptation to either higher mean temperature or fluctuating temperature. This work will take advantage of experimental evolution of Drosophila simulans with 15 replicates. The PhD student will investigate two traits, i.e. adaptation to mean temperature and fluctuation in temperature, in two experimental evolution treatments by combining time series analysis of Pool-Seq data with gene expression profiling and phenotypic assay.

Related literature:

  • Barghi, N. et al. Genetic redundancy fuels polygenic adaptation in Drosophila. PLoS biology 17, e3000128, doi:10.1371/journal.pbio.3000128 (2019)
  • Mallard, F., Nolte, V., Tobler, R., Kapun, M. & Schlötterer, C. A simple genetic basis of adaptation to a novel thermal environment results in complex metabolic rewiring in Drosophila. Genome Biology 19, 119, doi:10.1186/s13059-018-1503-4 (2018)
  • Schlötterer C. et al. Combining experimental evolution with next-generation sequencing: a powerful tool to study adaptation from standing genetic variation. Heredity 114, 431-440 (2015)
  • Orozco-terWengel, P. et al. Adaptation of Drosophila to a novel laboratory environment reveals temporally heterogeneous trajectories of selected alleles. Molecular ecology 21, 4931-4941, doi:10.1111/j.1365-294X.2012.05673.x (2012)


Efficient detection of variants of polygenic adaptation in Drosophila experimental evolution

Principal advisor: Andreas Futschik

In recent E&R experiments with Drosophila, some loci show an initial strong increase in allele frequency followed by a period where allele frequencies remain fairly constant. Such a plateauing pattern of allele frequency change may occur for different reasons but does not fit into a selective sweep framework (Orozco-terWengel et al., 2012). The same pattern has also been observed with other organisms. Indeed, using experimental data from outcrossed yeast populations, Kosheleva and Desai (2018) observed a diminishing strength of selection at the individual locus level while fitness is still increasing. They found evidence that this observed pattern results from recombination acting on a large number of weakly selected sites, with subsets of them initially in linkage disequilibrium. Their underlying (close to infinitesimal) model involving highly polygenic adaptation may in principle apply also to similar patterns found in Drosophila. Without fitness measurements there are also alternative explanations for a diminishing strength of selection at the locus level, such as a smaller number of unlinked loci both with weak and strong additive effects that are selected until a trait optimum is reached. Large, initially selected, blocks could then also be explained by hitchhiking on beneficial haplotypes. Epistasis or loci at which there is some form of heterozygote advantage may also lead to plateauing. A first goal is to find out whether it is possible to distinguish between these scenarios based on a typical experimental setup with Drosophila when fitness measurements are not available. Suitable summary statistics will be needed for this purpose, whose distributions differ between the scenarios. In Hermisson and Pennings (2017), footprints of rapid adaptation are discussed. Under the scenario proposed by the authors, summary statistics should also capture the pattern of decay of LD, and could possibly be derived from the dynamics of the correlation patterns of the allele frequency changes. Another approach would be to use machine learning based on a large number of simulated data to come up with suitable summary statistics. The software packages SLiM and MimicrEE are suitable for producing individual based simulation data in our context. Because yeast and Drosophila differ in many respects, we also plan to explore which experimental design parameters (in particular: population size, number of generations, number of replicates, number of sequencing time points, number of founding haplotypes) are needed to distinguish between the discussed scenarios.

Related literature:

  • Hermisson J and Pennings PS. Soft sweeps and beyond: understanding the patterns and probabilities of selection footprints under rapid adaptation. Methods Ecol. Evol. 8(6), 700–716. (2017) doi: 10.1111/2041-210X.12808
  • Kosheleva K and Desai MM. Recombination alters the dynamics of adaptation on standing variation in laboratory yeast populations. Mol. Biol. Evol. 35(1), 180–201. (2018) doi: 10.1093/molbev/msx278
  • Orozco-terWengel P, Kapun M, Nolte V, Kofler R, Flatt T and Schlötterer C. Adaptation of Drosophila to a novel laboratory environment reveals temporally heterogeneous trajectories of selected alleles. Mol. Ecol. 21(20), 4931–4941. (2012) doi: 10.1111/j.1365-294X.2012.05673.x

Evolution of gene expression

Principal advisor: Christian Schlötterer

While variation in gene expression is a major source of phenotypic diversity, our understanding of the processes driving changes in gene expression are still poorly understood. With the new sequencing technologies it will be possible to address many important questions about the evolution of gene expression.

The successful candidate will be part of a team of scientists studying adaptation of experimental Drosophila populations to temperature stress. She/he can build on several highly replicated Drosophila populations that have evolved under various temperature regimes.  We are planning to address the importance of plasticity in gene expression for adaptation to novel temperature regimes and how expression differences translate into fitness.

Related literature:

  • Jaksic, A.M., and Schlötterer, C. (2016). The interplay of temperature and genotype on patterns of alternative splicing in Drosophila melanogaster. Genetics 204, 315-325.
  • Chen, J., Nolte, V., and Schlötterer, C. (2015a). Temperature stress mediates decanalization and dominance of gene expression in Drosophila melanogaster. PLoS Genetics 11, e1004883. 10.1371
  • Chen, J., Nolte, V., and Schlötterer, C. (2015b). Temperature related reaction norms of gene expression: regulatory architecture and functional implications. Molecular Biology and Evolution 32, 2393-2402.


Functional characterization of beneficial alleles in Drosophila

Principal advisors: Kirsten-André Senti, Christian Schlötterer

One of the most amazing feats in biology is how natural selection enabled the adaption of species to different natural environments. Yet even a single Drosophila species thrives in diverse climates as equatorial Africa or Europe. From the natural variation within such species, we can – in principle - learn how evolution has shaped environmental adaption. Yet until recently finding the link between phenotype and genotype was a rare and difficult undertaking (1). However, today’s next generation sequencing offers an unprecedented view on the genetic variability. Combining phenotypic analyses with sequencing, Genome Wide Association Studies (GWAS) for instance enabled the identification of beneficial human alleles that protect against diseases (2).
Using paradigms such as starvation resistance and adaption to different temperatures, we have performed both GWAS as well as experimental evolution in combination with whole-genome re-sequencing of natural Drosophila populations (3). These experiments have established a number naturally occurring alleles that are associated with either increased survival under starvation stress or improved adaption to warmer or colder climates.
To validate these associations, we aim to employ the powerful CRISPR/Cas9 mediated genome engineering to functionally test if these natural gene variants indeed provide fitness advantages in well-controlled experimental settings. First, this project will establish a stable genome modification platform for natural Drosophila strains. Secondly, it will provide genetic and functional proof for beneficial adaptive alleles. Finally and in conjunction with our previous work, this approach will uncover those biological mechanisms that evolution tinkered with during adaption of natural populations.

Related literature:

  1. Sawyer L.A. et al., (1997) Natural variation in a Drosophila clock gene and temperature compensation. Science 278, 5346, 2117-2120
  2. Harper A.R. et al. (2015) Protective alleles and modifier variants in human health and disease. Nature Reviews Genetics, doi:10.1038/nrg4017
  3. Schlötterer C. et al. (2015) Combining experimental evolution with next-generation sequencing: a powerful tool to study adaptation from standing genetic variation. Heredity 114, 431-440

Genomic architecture of reverse selection

Principal advisor: Christian Schlötterer

Experimental evolution provides an excellent approach to study the adaptive response of selected alleles. Little is known about the dynamics of these selected alleles, when the selection pressure is reversed. In this project the genomic signatures will be studied using genomic time series allele frequency data from populations that evolved from the same founder in two opposing temperature regimes (hot and cold). Furthermore, allele frequency trajectories will be studied from populations, which experienced a reversed selection regime (first cold and then hot). The genomic data will be complemented with phenotypic data, such as life history traits and gene expression. The goal of this project is to determine if adaptation to hot and cold temperatures only reflects a different trait optimum or whether this are two different traits, each with a specific set of genes driving adaptation.

Related literature:

  • Teotonio, H., Chelo, I. M., Bradic, M., Rose, M. R. & Long, A. D. Experimental evolution reveals natural selection on standing genetic variation. Nature genetics 41, 251-257, doi:10.1038/ng.289 (2009)
  • Mallard, F., Nolte, V., Tobler, R., Kapun, M. & Schlötterer, C. A simple genetic basis of adaptation to a novel thermal environment results in complex metabolic rewiring in Drosophila. Genome biology 19, 119, doi:10.1186/s13059-018-1503-4 (2018)


Incipient speciation during adaptation to a new environment

Principal advisor: Christian Schlötterer

The emergence of new species is one of the most fundamental questions in biology, that is still not fully resolved. This project builds on the observation that flies which evolved for less than 200 generations in a novel environment are less likely to mate with flies from the ancestral population. In combination with the diverged gene expression of genes involved in sexual selection, these data suggest that the evolved flies are becoming reproductively isolated. The project will use state of the art phenotyping, including video-based behavioral assays, CHC and gene expression analyses and metabolomics to study this case of incipient speciation and shed light on the process of reproductive isolation occurring on time scales shorter than 200 generations.


Inference of selection parameters using whole genome data

Principal advisor: Claus Vogl

We will extend existing models to allow for exact inference of directional selection (or equivalently GC-biased gene conversion) in addition to mutation and drift using allele frequency spectra. Even short introns and fourfold degenerate sites, the best candidates for neutrally evolving nucleotide sites, show deviation from neutrality but can be described by the nearly neutral theory. A model with directional selection (or equivalently GC-biased gene conversion) with a scaled selection strength of about one, however fits the data (Vogl and Bergman, 2015; and unpublished data analyses). So far, we assumed mutation-selection-drift equilibrium for maximum marginal likelihood inference (Vogl and Bergman, 2015). To this end, we developed a model, where a single mutation segregates in a moderately sized sample (Bergman et al., 2018). This model is identical to a first order Taylor series expansion for small scaled mutation rates of the general mutation-drift model. We extended this model to splitting populations and non-equilibrium scenarios using orthogonal polynomials and now propose to incorporate also directional selection in this framework. We will apply the method to data from cosmopolitan and sub-Saharan African Drosophila populations to infer concurrently mutation, selection, and population demography.

Related literature:

  • Bergman J, Schrempf D, Kosiol C and Vogl C. Inference in population genetics using forward and backward, discrete and continuous time processes. J. Theor. Biol. 439, 166–180. (2018) doi: 10.1016/j.jtbi.2017.12.008
  • Vogl C and Bergman J. Inference of directional selection and mutation parameters assuming equilibrium. Theor. Popul. Biol. 106, 71–82. (2015) doi: 10.1016/j.tpb.2015.10.003

Long-term dynamics of adaptive alleles

Principal advisor: Christian Schlötterer

Experimental evolution is a powerful approach to detect selection signatures in evolving populations. Nevertheless, most studies focus on rather short-term evolution encompassing only a moderate number of generations. Computer simulations demonstrated that experiments over a larger number of generations provide much more power to detect the true target of selection. This project builds on Drosophila populations, which evolved for more than 200 generations in a novel temperature environment. With replicated time-series allele frequency data this project will take advantage of an unmatched data set in a naturally outcrossing species. The goal of this project is to characterize the genetic basis of temperature adaptation in Drosophila and the long-term dynamics of adaptive alleles.
 
Related literature:

  • Barghi, N. et al. Genetic redundancy fuels polygenic adaptation in Drosophila. PLoS biology 17, e3000128, doi:10.1371/journal.pbio.3000128 (2019)
  • Mallard, F., Nolte, V., Tobler, R., Kapun, M. & Schlötterer, C. A simple genetic basis of adaptation to a novel thermal environment results in complex metabolic rewiring in Drosophila. Genome biology 19, 119, doi:10.1186/s13059-018-1503-4 (2018)
  • Orozco-terWengel, P. et al. Adaptation of Drosophila to a novel laboratory environment reveals temporally heterogeneous trajectories of selected alleles. Molecular ecology 21, 4931-4941, doi:10.1111/j.1365-294X.2012.05673.x (2012)

Microbiome evolution in Drosophila

Principal advisor: Christian Schlötterer

The microbiome is a complex community of microorganisms which has a major influence on its host. While it has been shown that the composition of the microbiome is affected by many factors (e.g.:  diet), long-term transgenerational studies of microbiome dynamics are rare. Drosophila provides an excellent model to study microbiome evolution, because the microbiome is simple consisting of only a moderate number of taxa. In combination with the short generation time of Drosophila, it is possible to follow the evolution of the Drosophila microbiome across many generations.

This project will take advantage of many Drosophila populations, which have been evolving for more than 150 generations together with their associated microbiome. Using a combination of state-of-the-art metagenomics and targeted analysis of individual strains of ancestral and evolved microbiomes this project with provide unprecedented insights into the evolution of the microbiome.


Multi-measurement experimental evolution: How to combine evidence from different sources?

Principal advisor: Andreas Futschik

A typical Evolve and resequence (E&R) experiment involves replicate populations for which allele frequency changes are measured. Common methods to test for selection are either applied to each population separately or assume a consistent signal across replicates. However, inconsistent signals are frequently encountered across replicates. Methods that assume consistent allele frequency changes are then not very efficient. It is therefore of interest to develop new approaches that can combine evidence from different replicates and provide good power both for consistent and inconsistent signals. As a starting point, we will use the omnibus test developed by Futschik et al. (2018) which is based on independent p-values. This test provides good power no matter for how many tests k (≥1) the null hypothesis is false. An advantage of the method is its modularity, i.e., p-values from any statistical test can be taken as input, provided they are uniformly distributed under the null model. We intend to extend this approach in several directions: For instance, (i) by considering a whole time series of measurements simultaneously; (ii) by considering spatial response patterns along the chromosome, and taking into account linkage and haplotype structure; (iii) by simultaneous consideration of gene sets (as defined e.g., by GO-categories) to obtain the combined evidence for a GO-category; and (iv) by simultaneously considering different types of –omics data for genes that show a signal of selection in at least one of these categories while still controlling for multiple testing. Finally, as measurements at the single-cell level are currently becoming available, we intend to combine the evidence across cells to determine the genes that exhibit a response in at least some of the cells. Our intended method will not dilute sparse signals by averaging across all cells.

Related literature:

  •  Futschik A, Taus T and Zehetmayer S. An omnibus test for the global null hypothesis. Stat. Methods Med. Res. (2018) arXiv: 1709.00960

Polygenic adaptation: The roles of pleiotropy and epistasis

Principal advisor: Reinhard Bürger

Many traits important for ecological adaptation are quantitative traits, i.e., traits, such as body size, that vary continuously and can be measured on a scale. Typically, they are determined by contributions from many genetic loci. Often these loci also affect other traits, i.e., they have pleiotropic effects, and alleles exhibit dominance. Loci may also interact with each other, a phenomenon called epistasis. The aim of this project is to study the evolutionary dynamics of gene and genotype frequencies while the trait is adapting to a new optimum, i.e., after an environmental shift. Pleiotropy may be modeled, for instance, by deleterious effects on fitness but also by direct effects on other traits under selection. Problems of the following kind will be tackled. How many loci show a response? What is the magnitude of response at individual loci? In particular, do plateaus in the response occur, i.e., are complete or incomplete sweeps more common? What is the role of epistasis, dominance, and pleiotropy? How much variation of the response among replicates is expected? How does the response depend on initial frequencies (standing variation vs. new mutations), on the magnitude of allelic effects, and on population size. In the deterministic case, when population size is very large, the corresponding models are formulated as systems of nonlinear difference or differential equations. Otherwise, they are framed in terms of stochastic processes, in particular, branching processes and diffusion processes (depending on the question that shall be answered). The models will be studied by mathematical techniques from dynamical systems and by individual-based computer simulations. Therefore, a good background in mathematics is required.


The genetics of local adaptation in Arabidopsis thaliana

Principal advisor: Magnus Nordborg

We have been carrying out a number of long-term field experiments in Sweden, using native Swedish lines of A. thaliana (Long et al., 2013). Rather than just growing plants in plots and measuring seed set as a proxy for fitness, we established “natural” sites where the plants can compete over multiple generations, and sampled individuals throughout the experiment. Over 10,000 plants have been sampled, and we are currently in the process of sequencing them in order to map genes responsible for fitness differences using genome-wide association. The results will be compared with phenotypes (including transcriptome and epigenome) data taken from common-garden experiments carried out at the same sites. This will make it possible to investigate whether loci that show signs of selection are also associated with particular phenotypes.

Related literature:

  •  Long Q, Rabanal FA, Meng D, Huber CD, Farlow A, Platzer A, Zhang Q, Vilhjálmsson BJ, Korte A, Nizhynska V, Voronin V, Korte P, Sedman L, Mandáková T, Lysak MA, Seren Ü, Hellmann I and Nordborg M. Massive genomic variation and strong selection in Arabidopsis thaliana lines from Sweden. Nat. Genet. 45(8), 884–890. (2013) doi: Doi 10.1038/Ng.2678

The role of a nascent sex chromosome on interspecific patterns of allele sharing

Principal advisor: Christian Lexer

The role of sex chromosomes in species isolation is a topic of great current interest in evolutionary and population genetics (Charlesworth 2016 Annu Rev Plant Biol 67). While many well studied examples exist for fully evolved sex chromosomes, incipient sex chromosomes as in Populus provide a rare opportunity for study. In this PhD project, you will address patterns and determinants of genomic diversity and interspecific variant sharing in the nascent poplar sex chromosome for two different poplar species pairs at different stages of divergence, including hybrid zones for each pair. This will include a North American species pair with similar sex determination systems (both XY) and a Eurasian species pair with contrasting sex determination systems, Populus alba (ZW) and P. tremula (XY). You will use extensive whole genome and reduced representation library sequencing data for populations and hybrid zones in both species pairs to address (1) the interplay of selection and recombination in the nascent sex determination region in modifying interspecific gene flow, (2) the impact of a well characterized, extensive disease resistance (NBS-LRR) gene cluster in the nascent sex chromosome on interspecific variant sharing and genomic clines, and (3) the mechanisms that have constrained the evolution and full maturation of this enigmatic sex determination system.


Transposon polymorphism in Arabidopsis thaliana

Principal advisor: Magnus Nordborg

Because transposons are too repetitive to be sequenced using short-read sequencing methods, our understanding of transposon polymorphism is extremely limited. This has led to a literature of transposon evolution that is almost exclusively based on comparison between reference genomes — which is the wrong time-scale for highly dynamic transposons. Arabidopsis thaliana has low transposon content compared to other plants (less than 25% of the reference genome consist of annotated transposons), and it has been argued that transposons are mostly inactive in this species. However, we now know that this is not correct. Our analysis of the 1001 Genomes data suggests that roughly 50% of the annotated transposons are polymorphic, and that most of the insertions are in fact quite rare, i.e. most individuals do not carry them (they carry other insertions instead). Furthermore, we have identified lines that appear to carry twice as many transposons as the reference lines. This highlights the need for better data, and we are thus sequencing 200 genomes de novo using long-read technologies in order to get a comprehensive picture of transposon polymorphism and better understand the dynamics of transposons in populations. Analyzing these data will be perfect for a motivated PhD student with keen interest in population genetics.


Within-species consequences of genomic interactions in ecologically important species

Principal advisor: Christian Lexer

Adaptive introgression across ´porous´ species barriers has long been suspected to fuel a variety of eco-evolutionary processes, ranging from the origin of local adaptation within species to the explosive bursts of speciation seen during adaptive radiations. We have recently discovered a case of adaptive introgression between two North American members of the model forest tree genus Populus (Suarez-Gonzalez et al., 2016, 2018a, 2018b). This PhD project will test the ability of introgressed alleles to spread across the recipient species´ ranges, making use of extensive, available whole genome sequence data. Within an established international collaboration, you will address the mode and tempo of spread of introgressed alleles across species´ ranges using (1) a range of analytical tools from population genomics including HMM-based inference of local ancestry segments across genomes and populations, (2) spatially and ecologically explicit tools from niche modeling to project the spread of intogressed alleles into climate niche space. An interesting aspect will also be to evaluate the relative roles of gene flow, balancing selection, and variable sorting of ancestral alleles to genome-wide patterns of allele sharing in recently diverged species.

Related literature:

  • Suarez-Gonzalez A, Hefer CA, Christe C, Corea O, Lexer C, Cronk QCB and Douglas CJ. Genomic and functional approaches reveal a case of adaptive introgression from Populus balsamifera (balsam poplar) in P. trichocarpa (black cottonwood). Mol. Ecol. 25(11), 2427–2442. (2016) doi: 10.1111/mec.13539
  • Suarez-Gonzalez A, Hefer CA, Lexer C, Douglas CJ and Cronk QCB. Introgression from Populus balsamifera underlies adaptively significant variation and range boundaries in P. trichocarpa. New Phytol. 217(1), 416–427. (2018a) doi: 10.1111/nph.14779
  • Suarez-Gonzalez A, Hefer CA, Lexer C, Cronk QCB and Douglas CJ. Scale and direction of adaptive introgression between black cottonwood (Populus trichocarpa) and balsam poplar (P. balsamifera). Mol. Ecol. 27(7), 1667–1680. (2018b) doi: 10.1111/mec.14561

Fond zur Förderung der wissenschaftlichen Forschung
vetmed uni vienna
Gregor Mendel Institute of Molecular Plant Biology
Universität Wien