PhD Topics 2018

Please note: Application for topics marked with •+ is preferred for the present call and interested applicants will be treated with priority in the ranking.

•+•  Comparative population genomics in Drosophila species. Summary

•+•  Contribution of transposable elements to adaption during experimental evolution. Summary

•+•  Developing new statistical tools for the identification of adaptive QTLs. Summary

•+•  Evolution of gene expression. Summary

•+•  Evolution of phenotypic plasticity. Summary

•+•  Evolution of sex chromosomes in Drosophila species. Summary

•+•  Evolution of sperm competition in Drosophila. Summary

•+•  Functional characterization of adaptive QTLs. Summary

•+•  Genome-wide molecular dating Summary

•+•  Maximum likelihood inference of population genetic parameters using genome-wide data from nearly neutral sites. Summary

•+•  Sex-specific arms race between transposable elements and small RNAs. Summary

Topics

 

•+• Comparative population genomics in Drosophila species

Principal advisor: Claus Vogl

Population samples of genomic data are available for closely related Drosophila species, e.g., D. melanogaster, D. simulans, and D. yakuba. In D. melanogaster it is also possible to compare different populations, e.g., cosmopolitan with sub-Saharan African populations. These data reveal similarities among species and populations, but they also show differences, e.g., in nucleotide variability among chromosomes and chromosomal regions, in the AT:CG ratio, or in the frequency of inversions. While mining these data for differences seems interesting in its own right, we aim to connect such data with population genetic theory. This is of special interest, since some processes are so rare, e.g., spontaneous mutations, or weak, e.g., directional selection with strength on the order of drift, that they can only be studied with comparative data. Drosophila genomes provide currently the best data sets for such efforts.

 

•+• Contribution of transposable elements to adaption during experimental evolution

Principal advisor: Christian Schlötterer

The insertion of transposable elements affects the pattern of gene expression of neighboring genes. This project addresses the question to what extent transposable elements are mobilized by temperature stress and how mobilized elements contribute to adaptation. The project will have access to two D. melanogaster and three D. simulans populations, which have evolved in replicated experiments for more than 100 generations to hot environments. Using a combination of whole genome sequencing and RNA-Seq data, the impact of TEs will be studied.

 

•+• Developing new statistical tools for the identification of adaptive QTLs

Principal advisor: Christian Schlötterer

Experimental evolution is an excellent approach to study the response of adaptive Quantitative Trait Loci (QTLs) to environmental change. We have previously shown that loci contributing to adaptive traits have characteristic trajectories, which differ from neutral loci and loci evolving under directional selection. Combining quantitative genetics theory with state of the art statistical approaches, including deep learning, this project will develop methods to identify QTLs from replicated time series data. The new methods will be applied to an unparalleled data set consisting of 10 replicate D. simulans populations, which evolved for 150 generations. Sequencing data will be available in 10 generation intervals.

 

•+• 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.

Background:

1: 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.

2: 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

3: 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.

 

•+• Evolution of phenotypic plasticity

Principal advisor: Christian Schlötterer

Phenotypic plasticity is the ability of a single genotype to produce different phenotypes in response to environmental variation. The influence of phenotypic plasticity on the response of natural populations to selection is widely discussed, but no consensus has been reached yet. This project will take advantage of founder populations from two species, which were collected at the same location. These populations evolved for more than 100 generations in an extreme temperature environment. Contrasting the pattern of gene expression with RNA-Seq in ancestral and evolved populations at different temperatures, provides a powerful approach to test how plasticity in the ancestral populations affected the gene expression in the evolved populations.

 

•+• Evolution of sex chromosomes in Drosophila species

Principal advisor: Claus Vogl

Sex chromosomes experience evolutionary forces different from autosomes with respect to effective populations size, recombination and selection. While X-chromosomes number only 3/4th of the autosomes, they spend relatively more time in recombining females. Hemizygosity in males may expose deleterious mutations at low allele frequencies that would be shielded from selection by a functional allele in autosomes. While these differences in evolutionary forces are relatively small, i.e., in the neutral and nearly neutral region, they are nevertheless  expected to lead to genome-wide differences between sex-chromosomes and autosomes. We have developed statistical population genetic theory to analyze population genomic data in the neutral and nearly neutral parameter region that allow analysis of population genomic data. In this project we apply these methods to study characteristics of sex-chromosome evolution in closely related Drosophila species.

 

•+• Evolution of sperm competition in Drosophila

Principal advisor: Christian Schlötterer

This project focuses on post-copulatory competition of males, which is at least partially mediated by seminal fluid proteins. During mating Drosophila males transfer more than 200 different seminal fluid proteins to the female. Using a combination of RNA-Seq and genome-wide polymorphism data this project studies how sperm competition evolved in replicate populations evolving separately for more than 100 generations.

 

•+• Genome-wide molecular dating

Principal advisor: Carolin Kosiol

The PhD project is part of a larger project entitled “Genome-wide molecular dating”  The recent sequencing of genomes of closely related species and of many individuals from the same species enables the study of speciation and the inference of the history of populations. Standard phylogenetic methods reduce entire populations to single points in genotypic space by modelling evolution as a process in which a single gene mutates along the branches of a phylogeny. In this project, we envisage developing new theory and software to tackle the problem of species tree estimation and molecular dating genome-wide. Visits between St. Andrews, Vienna, Budapest and Aarhus for collaborations with Gergely Szöllösi and Asger Hobolth are possible.

The successful candidate should have a strong interest in applying quantitative methods and modelling to Biology. They will have a degree in Bioinformatics, Computer Science, Statistics, Mathematics, Physics or a related field. Prior experience with either population genetics, phylogeny or comparative genomics is a benefit. Preferably the candidate will have experience in programming language such as C, C++, Java and a scripting language such as Python or Perl.

 

•+• Functional characterization of adaptive QTLs

Principal advisor: Christian Schlötterer

It is widely accepted that most adaptive traits are encoded by many loci, each with a relatively small effect. Hence, in many cases the identification of such loci by population genetic tests is difficult, if not impossible. In an experimental evolution framework with replicated populations it is, however, possible to identify and characterize adaptive QTLs. Based on the analysis of D. simulans populations, which have evolved for more than 100 generations in a novel temperature environment, the PhD student will identify selected loci. After fine-mapping, the selected loci will be functionally characterized using CRISPR/Cas9 mediated transgenesis in combination with state of the art high-throughput phenotyping (RNA-Seq, translatomics and metabolomics).

 

•+• Maximum likelihood inference of population genetic parameters using genome-wide data from nearly neutral sites

Principal advisor: Claus Vogl

Kimura's neutral theory of molecular evolution provides a reference frame that leads to quantitative predictions that can be tested with molecular sequence data. Nucleotides in short introns and fourfold degenerate sites in coding sequences are generally thought to evolve neutrally. Yet tests applied to genome-wide data of these site classes from Drosophila species often reject neutrality. Deviations from neutrality seem to be caused by weak selection, i.e., selection with a strength that is on the order of drift. Such weak selection requires concurrent modeling of selection, mutation, and demography. Furthermore, neutrality tests usually assume equilibrium, an assumption that is unlikely to hold in natural populations that is often also rejected in tests. So far, most models for inferring population genetic forces either ignore deviations from neutral equilibrium or are based on the comparison of summary statistics from simulated data with the observed data, which involves loss of information. Using diffusion theory and orthogonal polynomials, we have developed probabilistic models that allow for maximum (marginal) likelihood inference of population genetic parameters. So far our models allow for deviations from equilibrium and for selection, but not both yet. Aims of the current project are to incorporate deviations from equilibrium concurrently with selection, to incorporate migration, and to allow for sampling via pooled sequencing. The methods are to be implemented as "R"-packages and applied to Drosophila sequence data.

 

•+• Sex-specific arms race between transposable elements and small RNAs

Principal advisor: Qi Zhou

Transposable elements (TE) are genomic parasites that may harm other genes’ function if not properly regulated. It is well established now in metazoans, TEs are silenced through a germ-line specific small RNAs called piRNAs. As a paradox, the male-specific Y chromosomes have been found to universisally accumulate massive TEs due to a lack of homologous recombination. It is unknown, how these Y-specific TEs are regulated, and their impact on the host genome during evolution. This project will use Drosophila species as model, and use novel functional genomic approaches to study the ongoing arms race between TEs and small RNAs during the evolution of Y chromosomes. The candidate PhD student has the chance to work together with other well-trained bioinformaticians and evolutionary biologists in the group. The preferred candidate is expected to have background in Drosophila genetics and evolutionary biology.

Related papers to the project:

http://www.sciencedirect.com/science/article/pii/S016895251000171X

https://www.nature.com/nrg/journal/v14/n2/abs/nrg3366.html

 

Dynamics of a selfish DNA invasion

Principal advisor: Robert Kofler

Few people are aware that our genomes are filled with parasites. These so called transposable elements (TEs) selfishly spread in our genomes and may even cause diverse diseases. TEs have been remarkably successful: they occur in all eukaryotic species and constitute about 50% of our genomes.

TEs are also known to frequently invade novel species by horizontal transfer. They rapidly spread within afflicted populations, while the hosts struggle to contain their spread in order to avert major damage. However, after some time most hosts succeed in controlling the invasion of a TE, but it is largely unknown how this is exactly achieved. To shed light on this  we will investigate TE invasions at high resolution using cutting edge technologies such as small RNA sequencing, RNA-Seq, phenotypic assays and Pool-Seq.

This work will allow the student to shed light on the invasion of parasitic DNA within a young and international team, get in contact with cutting-edge technologies and receive a first-rate training in bioinformatics. The project will involve 60% lab-work and 40% computer work. Some wet-lab experience (e.g. PCR) and programming skills (e.g. R or Python) would be beneficial.

 

Epigenetic variation in Arabidopsis

Principal advisor: Magnus Nordborg

It has long been argued that epigenetic transgenerational inheritance could play an important role in adaptation (as well as in breeding and human complex trait variation). However, while the existence of such inheritance is no longer in doubt (at least not in plants, where DNA methylation can clearly be inherited; see Grossniklaus et al. 2013; Heard and Martienssen 2014), evidence that it plays an adaptive role is mostly limited to geographic correlations between methylation and the environment that are suggestive of selection, but prove little (Verhoeven, vonHoldt, and Sork 2016).

Our recent studies in Arabidopsis thaliana have uncovered remarkable geographic patterns that will enable us to address this issue (Dubin et al. 2015; Kawakatsu et al. 2016). Analysis of the genomes, transcriptomes, and methylomes of over 1,000 natural inbred lines grown in the same environment revealed genome-wide variation in DNA methylation that was strongly correlated with the environment of origin of the lines — implying either that they carry an epigenetic memory of their ancestral environment, or that the divergence in methylation is simply due to genetics. These two explanations are not mutually exclusive. In support of the former, DNA methylation is known to be heritable; in support of the latter, genome-wide association studies (GWAS) and crosses revealed that much of the variation clearly has a genetic basis.

My lab is currently trying to determine the extent to which these two explanations are responsible for the observed patterns, i.e., their proximal cause. We also seek to elucidate their ultimate cause, i.e., the evolutionary mechanisms that lead to such strong environment correlations. Research will involve analysis of large genomic data sets, and the requisite skills are required.

Background:

Dubin, Manu J., Pei Zhang, Dazhe Meng, Marie-Stanislas Remigereau, Edward J. Osborne, Francesco Paolo Casale, Philipp Drewe, et al. 2015. “DNA Methylation in Arabidopsis Has a Genetic Basis and Shows Evidence of Local Adaptation.” Genomics. eLife 4 (May). doi:10.7554/eLife.05255.

Grossniklaus, Ueli, William G. Kelly, Bill Kelly, Anne C. Ferguson-Smith, Marcus Pembrey, and Susan Lindquist. 2013. “Transgenerational Epigenetic Inheritance: How Important Is It?” Nature Reviews. Genetics 14 (3): 228–35.

Heard, Edith, and Robert A. Martienssen. 2014. “Transgenerational Epigenetic Inheritance: Myths and Mechanisms.” Cell 157 (1). Elsevier Inc.: 95–109.

Kawakatsu, Taiji, Shao-Shan Carol Huang, Florian Jupe, Eriko Sasaki, Robert J. Schmitz, Mark A. Urich, Rosa Castanon, et al. 2016. “Epigenomic Diversity in a Global Collection of Arabidopsis Thaliana Accessions.” Cell 166 (2): 492–505.

Verhoeven, Koen J. F., Bridgett M. vonHoldt, and Victoria L. Sork. 2016. “Epigenetics in Ecology and Evolution: What We Know and What We Need to Know.” Molecular Ecology 25 (8): 1631–38.

 

Genetic footprints of adaptive introgression

Principal advisor: Joachim Hermisson

Background: In nature, diverged populations or incipient species can often still exchange genetic material. This is particularly interesting if species exchange adaptive genes. Recent research has shown that adaptive introgression is indeed an important source for new adaptations in many animal and plant species. In particular, it has been shown that there has been adaptive gene flow from archaic humans (such as Neanderthals or Denisovans) to ancient modern humans.

Project: Haplotype patterns after adaptive gene introgression. The aim of the planned project is to characterize the expected footprint of adaptive introgression and to develop statistical methods to detect such footprints in genome-wide polymorphism data. It has previously been shown that tests based on haplotype patterns are the most powerful ones to detect events of recent adaptation in human populations. We therefore will focus on the haplotype patterns generated by adaptive introgression. We will address question such as: What is the distribution of introgression tract lengths around the beneficial allele for a single successful introgression event? How many distinct pieces of introgressed material do we expect to find – and at which distance to the beneficial allele? How do linked deleterious alleles (which may either hitch-hike or not) affect these results? We will use analytical theory based on branching processes and coalescent simulations. Knowledge about the haplotype pattern is very relevant, in particular, to link any theoretical results to data. In the context of the graduate school, we will cooperate with Christian Schlötterer, who will study the introgression of single hot-temperature-adapted genotypes into a cold-adapted population under the hot selection regime. We will also apply the methods to Human data sets.

 

Macroevolutionary dynamics of selfish DNA unravelled by third generation sequencing

Principal advisor: Robert Kofler

Few people are aware that our genomes are filled with parasites. These so called transposable elements (TEs) selfishly spread in our genomes and may even cause diverse diseases. TEs have been remarkably successful: they occur in all eukaryotic species and constitute about 50% of our genomes.

Despite the fundamental importance of TEs little is known about their long term evolution.

In this work we will sequence populations of closely related Drosophila species using the most recent long read technologies (PacBio and Oxford Nanopore). This will allow to unravel the evolutionary dynamics of TEs with unprecedented resolution and shed light on the following questions:

  • How fast are these parasites spreading in genomes?
  • Are invasions of these parasites influencing the large-scale evolution of genomes (e.g. inversions, translocations)?
  • How frequent is the invasion of a novel genomic parasite in the course of evolution?
  • Can we also find evidence for the death of a TE?

This work will allow the student to get in contact with cutting edge sequencing technologies, shed light on the evolution of genomes within a young and international team and receive a first-rate training in bioinformatics. The project will involve 20% lab-work and 80% computer work. Some programming skills (e.g. R or Python) and some wet-lab experience (e.g. PCR) would be beneficial.

 

New methods for modelling and analysis of data from experimental evolution

Principal Advisor: Andreas Futschik

As sequencing data are becoming less and less expensive, experiments to investigate the genomic response to selection are carried out at larger and larger scales. At the Vienna Graduate School of Population Genetics such experiments are carried out using Drosophila as a model organism. These experiments typically involve replicate populations and look for instance at unusual allele frequency changes. A further typical feature of such experiments is that whole pools of individuals are sequenced together at several time points. With more and more data coming in, it became apparent that adaptive signals are often more complicated than initially anticipated. This leads to new interesting methodological challenges with the analysis of such data.

The goal of the project will be the evaluation of existing methods, as well as the development of new statistical methods that help to investigate the genetic response to selection pressure, as occurring for instance when populations adapt to new environments.

The successful applicant should have good programming skills. As this project will take place at the interface between statistics and population genetics, interest in both areas will be important. Some existing knowledge in one of these fields will be a plus, but can also be acquired during the course of the PhD studies.

 

Statistical inference concerning population genetic parameters from repeated genomic measurement data

Principal Advisor: Andreas Futschik

High dimensional data, such as those produced from DNA and RNA sequencing experiments lead to exciting new challenges for the field of statistics. The proposed project is connected to the modelling of such data. Existing statistical methods will need to be adapted and new methods developed.

This Ph.D. project will provide a motivated student with the opportunity to participate in such research, and to apply new methods to analyze real population genetic data.

Nowadays, population genetics relies to a large extent on the analysis of next generation sequencing data. Such data are challenging to handle as they are high dimensional. The sample size can be fairly large, when whole pools of organisms are simulated simultaneously. When individual organisms are sequenced separately, they tend to be considerably smaller. A further characteristic of such data is the complex error structure, with error components including the sampling from the population, genetic drift, as well as sequencing and alignment errors.  If whole pools of individuals are sequenced, this would add a further component of variance.  Statistical models have to take these error components properly into account, in order to provide valid conclusions. Previous publications by Futschik et al. deal with the proper estimation of population genetic parameters (such as the mutation rate, the effective population size, and the population recombination rate) under such a setting.

Project: An important issue is to disentangle local features such as selection from global features such as demography using genomic data at repeated time points. One question will be to estimate the proportion of the genome affected by selection. Empirical Bayes in the context of mixture models could be a promising approach to tackle such questions.  A further question will be to investigate how estimates of global parameters are affected by local model deviations e.g. due to selection. Subsequently we want to optimize the separation between local and global features in terms of the performance of estimates for global parameters.

 

The adaptive value of diversity produced by recurrent whole genome doubling

Principal advisor: Ovidiu Paun

Whole genome doubling (WGD) and hybridization profoundly shaped plant genome evolution. However, most neopolyploids show poor fitness and fail to establish. To be successful, first generation allopolyploids must quickly adjust their genome and function, thereby altering their ecological properties and adaptive success, as a function of their environment. The duplicated nature of polyploids buffers more effectively deleterious alleles and provides genome-wide opportunities for adaptive evolution. Recurrent origins of polyploids are widespread and provide natural replicates to study mechanisms of rapid adaptation to divergent environments.

This project will combine molecular and ecological investigations in a fairly young polyploid complex in Dactylorhiza, comprising sibling terrestrial orchids with divergent ecological preferences. Specifically, to complement ongoing analyses of the nature of the extant molecular diversity in the D. majalis complex, we will interrogate the adaptive value of this diversity within reciprocal transplant experiments in the Alps and Scandinavia. We will shed light on the links between genotype, epigenotype and environmental conditions, by focusing on the environmental sensitivity of gene expression (with RNAseq) and of post-transcriptional regulation by small RNAs (with smRNAseq), exploring also in detail the link between DNA methylation patterns and expression of duplicated genes.

 

FWF - Der Wissenschaftsfond Partner: FWF - Der Wissenschaftsfond
Vetmed Uni Vienna Partner: Vetmed Uni Vienna
Max F. Perutz Laboratories Partner: Max D. Perutz Laboratories
Gregor Mendel Institut Partner: Gregor Mendel Institute
Uniwien Partner: Uniwien