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PhD Topics 2018

  • 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
  • more 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:

  • 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.

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


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