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PhD Topics 2022

  • Did selfish DNA from Neanderthals infect our human genomes? Summary
  • Evolution from de novo mutations - influence of elevated mutation rates. Summary
  • Evolution of sex-specific neuronal signaling. Summary
  • Impact of para-mutations on the invasion dynamics of TEs. Summary
  • Inference of selection signatures from time-series data. Summary
  • Invasion dynamics of different TEs. Summary
  • Leveraging long-read sequencing for population genetics of TEs. Summary
  • Long-term dynamics of local Drosophila populations. Summary
  • Studying the evolution of gene expression with single cell RNA-Seq. Summary
  • Studying speciation during experimental evolution. Summary
  • Temperature adaptation in Drosophila: phenotypic adaptation. Summary

More topics


Did selfish DNA from Neanderthals infect our human genomes?

Life is a struggle for survival where parasites prey on their hosts and hosts combat their parasites. Surprising to many, this battle also rages in our genomes. Parasitic DNA spreads within genomes, even if this harms the host’s health. These parasitic sequences, also called transposable elements (TEs) have been remarkably successful, constituting more than 50% of our human genomes. Some of these TEs are closely related to viruses.

It is unclear when and how TEs accumulated in our genomes. The broad availability of ancient DNA, i.e. DNA extracted from preserved human bones, offers a unique opportunity to address these questions. We previously established a pipeline to assess the amount of TEs in human genomes. In this work we will extend this pipeline to ancient DNA. We will first validate the pipeline and then use it with available ancient DNA data. This will provide us with the first high-resolution history of the evolution of repetitive DNA in human genomes. We will ask if our ancestors‘ mating with Neanderthals and Denisovans was responsible for introducing novel TEs into human genomes, which subsequently spread within worldwide populations.


Evolution from de novo mutations - influence of elevated mutation rates

Most new mutations are deleterious and will be purged from evolving populations. This PhD project will evaluate how a genetically identical population of fruit flies can adapt to a new polygenic phenotype by novel mutations. By contrasting populations with different mutation rates and population sizes this project seeks to characterize the adaptive response of a polygenic trait. Since only a few mutations are expected to be beneficial, this project provides the opportunity to identify and characterize individual alleles contributing to a highly polygenic trait.

The project is particularly well-suited for students with a keen interest to combine experimental fly work with state of the art bioinformatic analyses characterizing the trajectories of selected alleles. Candidates are provided the opportunity to test beneficial alleles in transgenic assays.  Experience with CRISPR/Cas9 is beneficial for the functional characterization, but not required for the project.


Evolution of sex-specific neuronal signaling

Previous work showed that neuronal signaling evolved in Drosophila simulans from Florida in response to a new temperature regime. Interestingly, this evolutionary response occurred in a sex-specific manner: males and females modified different signaling pathways.

This PhD project will use a combination of single cell RNA-Seq and behavioral analyses to identify the selective forces driving this sex specific signaling. A comparison to flies from other populations and species that evolved under the same selection regime will inform us to what extent this evolutionary response is population specific or provides a general temperature adaptation.

Future PhD students should have a vivid interest in exploring new data analyses and develop new innovative phenotyping methods.

References:

  • Hsu SK, Jaksic AM, Nolte V, Lirakis M, Kofler R, Barghi N, Versace E, Schlötterer C. 2020. Rapid sex-specific adaptation to high temperature in Drosophila. Elife 9.
  • Jaksic AM, Karner J, Nolte V, Hsu SK, Barghi N, Mallard F, Otte KA, Svecnjak L, Senti KA, Schlötterer C. 2020. Neuronal function and dopamine signaling evolve at high temperature in Drosophila. Molecular biology and evolution doi:10.1093/molbev/msaa116


Impact of para-mutations on the invasion dynamics of TEs

Transposable elements (TEs) are stretches of parasitic DNA that multiply in our genomes. The genomes of most species are riddled with remnants of past TE invasions. It was long thought that a TE invasion is stopped when the proliferating TE randomly jumps into distinct genomic regions (the piRNA clusters) which produce small RNAs (the piRNAs) that silence the TE. Although this idea is well supported by experimental data, recent work calls this model into question. For example, deletion of large piRNA clusters did not lead to an upregulation of TEs. Instead, dispersed TE insertions may be responsible for generating the piRNAs that silence TEs.

Here we will use computer simulations of TE invasions to test whether para-mutations could resolve these conflicting results. Directed by host piRNAs, paramutations may convert dispersed TE insertions into piRNA producing loci. But where are the very first piRNAs coming from? The emergence of the very first piRNAs could still be triggered by random insertions into a piRNA cluster. We will use our in-house simulation software to explore this question. We will also utilize experimental data to support our conclusions. Further questions that may be addressed with this simulation framework include: i) Could TEs have evolved an insertion bias into regions that control their spread (e.g. piRNA clusters) since this would reduces the fitness burden to the host? and ii) What is the evolutionary fate of a newly emerged piRNA cluster (e.g. fixation or loss dependent on the parameters)?


Inference of selection signatures from time-series data

Molecular population genetics has a long-standing tradition to infer selection signatures from genomic data. Most of the developed methods rely either on a single population or the contrast of multiple populations with different selection pressure in the past. With the increasing availability of time series data from ancient DNA and experimental evolution, it has become possible to study time-series data. Hence, the temporal pattern of allele frequency changes provides extremely rich information to distinguish selection from neutral patterns. This PhD project builds on an exceptionally powerful experimental evolution study, with 15 replicate Drosophila populations adapting to a novel environment for more than 100 generations. Genomic data are available in 10 generation intervals to study the allele frequency trajectories at high temporal resolution.

The future PhD student will have the opportunity to analyze the best time series data set available for a sexual organism. Hence, experience with handling large data sets is clearly a benefit and candidates with a keen interest to advance currently available statistical methods to analyze time-series data are particularly welcome to apply.

References:

  • Vlachos, C. Burny, C., Pelizzola, M., Borges, R., Futschik, A., Kofler, R. & Schlötterer, C. Benchmarking software tools for detecting and quantifying selection in evolve and resequencing studies. Genome Biology 20, 169, doi:10.1186/s13059-019-1770-8 (2019).
  • Taus, T., Futschik, A. & Schlötterer, C. Quantifying Selection with Pool-Seq Time Series Data. Molecular Biology and Evolution 34, 3023-3034, doi:10.1093/molbev/msx225 (2017).
  • Barghi, N., Tobler, R., Nolte, V., Jakšić, A. M., Mallard, F., Otte, K. A., Dolezal, M., Taus, T., Kofler, R. & Schlötterer, C. Genetic redundancy fuels polygenic adaptation in Drosophila. PLoS Biology 17, e3000128, doi:10.1371/journal.pbio.3000128 (2019).


Invasion dynamics of different TEs

Life is a struggle for survival where parasites prey on their hosts and hosts combat their parasites. Surprising to many, this battle also rages in our genomes. Parasitic DNA spreads within genomes, even if this harms the host’s health. These parasitic sequences, also called transposable elements (TEs) have been remarkably successful, constituting more than 50% of our genomes.

TEs are closely related to viruses and frequently invade novel species. It is unclear how the sequence of the TE influences invasion dynamics. To shed light on this important question we will engineer multiple different versions of a TE (the P-element), introduce them into several Drosophila species and study their invasion dynamics. We will rely on cutting edge technologies such as small RNA sequencing, RNA-Seq, and long-read sequencing (Oxford Nanopore).


Leveraging long-read sequencing for population genetics of TEs

Transposable elements (TEs) are stretches of parasitic DNA that multiply in our genomes. The genomes of most species are riddled with remnants of past TE invasions. Interestingly the TE composition differs dramatically among species, with some species having many TEs and others having very few. Which factors determine the abundance and distribution of these TEs within species? Although of central importance many open questions remain.

The newest long-read sequencing technologies, like Oxford Nanopore Sequencing, promise to shed light on these open questions as long-read sequencing will finally provide us with a complete picture of the TE landscape in populations. In this project we will sequence multiple individuals from different Drosophila species using long-read sequencing. Using novel bioinformatics approaches and linear-models we will then i) ask which factors influence the distribution of TEs in genomes (e.g. length, genomic context, family, small RNA abundance) ii) determine if the impact of these forces differs among species and iii) test if the composition of regions thought to control TE invasions (i.e. piRNA clusters) agrees with expectations based on simulations.


Long-term dynamics of local Drosophila populations

Most inference of adaptation in natural populations is either based on genomic polymorphisms patterns of a single population or the contrast between populations adapted to different environments. Since time series data provide a very powerful approach to distinguish selection from other evolutionary forces changing allele frequencies, longitudinal sampling of a single population provides a hitherto underexplored approach to study the evolutionary dynamics of natural populations. The future PhD student will be granted access to an unique collection of samples covering more than 10 years with multiple samples throughout the entire season. This outstanding data set will provide new insights in the dynamics of local populations and their evolutionary response to a changing climate.

This project is particularly well suited for PhD students with a background in population genetics, who are interested to develop new cutting edge data analyses that incorporate time series data to distinguish selection from other forces. Whole genome polymorphism Pool-Seq data will be available as well as sequence data from individual flies to facilitate haplotype-based analyses.


Studying the evolution of gene expression with single cell RNA-Seq

Previous work from our laboratory demonstrated that adaptation to a novel temperature regime is accompanied by changes in gene expression-frequently in a sex-specific manner. Until now, we focused on the analysis of whole body adults, but the extent to which these expression differences are determined by altered gene expression patterns of individual cells is not yet understood. This PhD project aims to address this question using large-scale single cell RNA-seq on a population level. This will provide unprecedented insights into the evolution of gene expression in populations. The project provides an excellent opportunity for PhD students with strong interest to combine latest bioinformatics methods with population genetic theory.

References:

  • Hsu SK, Jaksic AM, Nolte V, Lirakis M, Kofler R, Barghi N, Versace E, Schlötterer C. 2020. Rapid sex-specific adaptation to high temperature in Drosophila. Elife 9.
  • Mallard F, Nolte V, Schlötterer C. 2020. The evolution of phenotypic plasticity in response to temperature selection. Genome Biol. Evol. 12: 2429-2440.
  • Zappia L, Theis FJ. 2021. Over 1000 tools reveal trends in the single-cell RNA-seq analysis landscape. Genome Biology 22:301


Studying speciation during experimental evolution

This project will take advantage of several sets of replicated populations, which are evolving to a novel environment. In depth analysis of one of these sets indicated that in less than 200 generations both pre- and post-mating reproductive isolation has developed (Hsu et al.). We showed that the underlying mechanisms align very well with ecological speciation and mutation-order speciation. Using additional experimental populations evolved either from different founders or distinct environments this project will evaluate under which conditions reproductive isolation can occur and which types of speciation mechanisms can be observed. The project offers an exciting combination of behavioral analyses, temperature-related phenotypes and molecular analyses including RNA-Seq, whole genome sequencing and GWAS.

Reference:

  • Hsu, S.-H., Lai, W.-Y., Novak, J., Lehner, F., Jakšić, A. M., Versace, E. & Schlötterer, C. Pre- and post-mating reproductive isolation evolve independently during rapid adaptation to high temperature. bioRxiv 2021.11.08.467720; doi:10.1101/2021.11.08.467720 (2021)


Temperature adaptation in Drosophila: phenotypic adaptation

In the wake of global warming, adaptive strategies to cope with such environmental changes become essential for a broad range of organisms. We are using the genetic model organism Drosophila to study the adaptive strategies. This PhD project will characterize the phenotypic changes required for fruit flies to be successful at high temperatures and integrate the phenotypic data with available genomic and transcriptomic data. The future PhD student take advantage of highly replicated experimental populations, from three Drosophila species, which evolved for more than 60 generations in a novel hot temperature regime. We will determine population and species-specific phenotypic responses to laboratory induced climatic change.

The future PhD student is expected to have a vivid interest to develop and establish new phenotyping methods.
 
References:

  • Kellermann, V., Hoffmann, A. A., Kristensen, T. N., Moghadam, N. N. & Loeschcke, V. Experimental evolution under fluctuating thermal conditions does not reproduce patterns of adaptive clinal differentiation in Drosophila melanogaster. Am Nat 186, 582-593, doi:10.1086/683252 (2015).
  • Hsu, S. K., Jakšić, A. M., Nolte, V., Lirakis, M., Kofler, R., Barghi, N., Versace, E. & Schlötterer, C. Rapid sex-specific adaptation to high temperature in Drosophila. Elife 9, doi:10.7554/eLife.53237 (2020).
  • 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).
Fond zur Förderung der wissenschaftlichen Forschung
vetmed uni vienna
Gregor Mendel Institute of Molecular Plant Biology
Universität Wien