Sommer Lab Logo

Evolutionary Genomics and Bioinformatics

Project leader:
Christian Rödelsperger

Department:
IV - Evolutionary Biology

Director:
Ralf. J. Sommer

Office:
Kostadinka Krause
Spemannstrasse 39
D-72076 Tübingen
Germany
Phone: +49 7071 601 440/441
Fax: +49 7071 601 498

Introduction

Recent developments in sequencing technologies have dramatically extended our capabilities to study how genomes control the development from a fertilized egg to a complete organism, how they interact with the environment, and how they evolve over time. Using the nematode Pristionchus pacificus as a main research subject, our group is embedded in the highly inter-disciplinary Sommer lab in order to contribute to the annotation, analysis, and decoding of the P. pacificus genome. One major part of our work is the analysis of sequencing data from natural isolates and genetic screens to link genotypes to phenotypes for a number of traits and to investigate how the underlying genomic loci evolved. As part of this work, we are using comparative genomic (cross-species) and population genomic (intra-species) approaches to discover general patterns of genome evolution that might also apply in other organisms such as other nematodes like C. elegans but also vertebrates, flies and plants. 

Projects

Decoding the P. pacificus genome

General scheme of association mapping in P. pacificus. (A-B) Bordering behaviour of
particular P. pacificus strains is one example for different phenotypes that are studied
in our lab (Moreno et al. 2016). (C-D) We have mapped and used a dumpy mutant
as a morphological marker to optimize genome editing protocols in P. pacificus
(Witte et al. 2015). E) Recombinant inbred lines (RILs) were generated from a
cross of parental lines that differ in phenotype (e.g. dpy vs. wt). F) Genotypic and
phenotypic data is combined to identify the genomic regions with strongest association,
see Witte et al. 2015 for further details.

It is relatively easy to sequence a genome, however to understand the function and biological significance of individual genes, still takes an enormous amount of experimental work. One major part of our work is to help in linking genotype to phenotype. In close collaboration with other scientist from our department, we work on identifying the genetic basis for various traits. This involves the analysis of whole-genome sequenced mutant strains (Ragsdale et al. 2013), as well as statistical analyses of the association between genotype and phenotype based on artificial crosses (Moreno et al. 2016) and population-scale resequencing data (McGaughran et al. 2016). Characterizing the identified loci at a within-and cross-species level can give a further insights into the evolution of associated traits.

Genome evolution in Pristionchus nematodes

While only around 20% of P. pacificus genes have an exact correspondance in C. elegans,
most genes have undergone duplication events in either of the lineages or
are completely unknown.

P. pacificus  was among the first nematodes with a seqeunced genome.  Initial analysis showed that only around 20% of the 20,000-30,000 P. pacificus genes have one-to-one orthologs in C. elegans. Furthermore, around one third of genes, so called orphan genes, do not have homologs in any other sequenced nematode genome and have therefore absolutely no functional annotation. The remaining part is composed of genes that have undergone lineage-specific duplications in either the C. elegans or the P. pacificus lineage. Thus, gene duplication and generation of novel genes had dramatic impact on the gene repertoire of Pristionchus nematodes and in individual cases we have shown that both classes of lineage-specific genes can control ecologically important traits and developmental decisions (Ragsdale et al. 2013, Mayer et al. 2015). Using micro and macroevolutionary approaches we study the genomic processes that generate new genes and the evolutionary forces that act on them (Prabh and Rödelsperger 2016). 

Comparative transcriptomics

Most developmentally regulated genes in P. pacificus arose from lineage-specific duplications that
generated closely related gene copies with highly similar expression profiles (Baskaran et al. 2015).

P. pacificus and C. elegans have quite distinct natural histories and are specialized to very different microhabitats. Identifying the genes, that are activated in response to various environmental cues such as pathogen exposure or during the growth arrested dauer stage provides insights into how nematodes interact with their environment (Baskaran et al.  2015 , Lightfoot et al. 2016). In addition, tissue and stage-specific analysis of gene expression can be combined with phylogenetic analysis in order to identify main drivers of gene expression evolution. Thus, we have recently shown that positive selection on gene dosage has likely acted on developmentally regulated genes by generating additional gene copies that all shared the same expression profile (Baskaran et al.  2015).

Population genomics

All the changes that generated the phenotypic diversity in animals have initially been introduced as mutations into single populations and reached fixation in individual lineages. To better understand genetic and phenotypic diversity at a macroevolutionary scale, we have to study the population genetic processes that generate this diversity at the first place. Initial analysis of whole-genome resequencing data from more then hundred globally sampled P. pacificus strains has demonstrated that that large parts of the genome are under strong negative selection (Rödelsperger et al. 2014 and Baskaran and Rödelsperger 2015, Mc Gaughran et al. 2016) and that variation in recombination can drive linked neutral or even deleterious alleles to fixation.

A) Split-network showing phylogenetic relationship between 104 genomes of P. pacificus (Rödelsperger et al. 2014)
B) Comparisons at different time-scales show that most deleterious are quickly eliminated by negative selection, however a fraction of weakly deleterious alleles is still segregating in populations (Weller et al. 2014, Rödelsperger et al. 2014).

Pristionchus genomic infracture

Despite the fact that the P. pacificus genome is still one of the best published nematode genomes, ongoing work investigates to what extent genome and annotations can be improved. We maintain a webserver pristionchus.org, which allows access to most of our genomic data sets and we collaborate with wormbase.org to give a broader community access to our data.

Scientists involved:

  • Dr. Christian Rödelsperger (Project Group Leader)
  • Praveen Baskaran (PhD student - gene duplication)
  • Neel Prabh (PhD student - orphan genes)

Alumni:

  • Kevin Menden (Student research assistant - antisense transcription)
  • Dr. Gabriel Markov (PostDoc – evolution of metabolic pathways)

Selected References

Baskaran, P., Rödelsperger, C., Prabh, N., Serobyan, V., Markov, G. V., Hirsekorn, A. & Dieterich, C. (2015): Ancient gene duplications have shaped developmental stage-specific expression in Pristionchus pacificus. BMC Evol Biology, DOI: 10.1186/s12862-015-0466-2.

Baskaran, P. & Rödelsperger, C. (2015): Microevolution of Duplications and Deletions and Their Impact on Gene Expression in the Nematode Pristionchus pacificusPLoS One, DOI: 10.1371/journal.pone.0131136.

Mayer, M. G., Rödelsperger, C., Witte H., Riebesell, M. & Sommer, R. J. (2015): An orphan gene regulates intraspecific competition in nematodes by copy number variation. PLoS Genetics11, DOI: 10.1371/journal.pgen.1005146. 

McGaughran, A., Rödelsperger, C., Grimm, D.G., Meyer, J.M., Moreno, E., Morgan, K., Leaver, M., Serobyan, V., Rakitsch, B., Borgwardt, K.M. & Sommer, R.J. (2016):  Genomic Profiles of Diversification and Genotype-Phenotype Association in Island Nematode Lineages. Molecular Biology and Evolution, 33 (9):2257-72, DOI: 10.1093/molbev/msw093.

Meyer, J.M., Markov, G.V., Baskaran, P., Herrmann, M., Sommer, R.J., Rödelsperger, C. (2016): Draft Genome of the Scarab Beetle Oryctes borbonicus on La Réunion Island. Genome Biol Evol. 8(7):2093-105, DOI: 10.1093/gbe/evw133.

Moreno, E., McGaughran, A., Rödelsperger, C., Zimmer, M. & Sommer, R.J. (2016): Oxygen-induced social behaviours in Pristionchus pacificus have a distinct evolutionary history and genetic regulation from Caenorhabditis elegans. Proc Biol Sci., 283 (1825):20152263., DOI: 10.1098/rspb.2015.2263.

Lightfoot, J.W., Chauhan, V.M., Aylott, J.W. & Rödelsperger, C. (2016):  Comparative transcriptomics of the nematode gut identifies global shifts in feeding mode and pathogen susceptibility. BMC Res Notes. 9:142, DOI: 10.1186/s13104-016-1886-9.

Prabh,N. & Rödelsperger, C. (2016): Are orphan genes protein-coding, prediction artifacts, or non-coding RNAs? BMC Bioinformatics. 17(1):226, DOI: 10.1186/s12859-016-1102-x.

Ragsdale, E. J., Müller, M. R., Roedelsperger, C. & Sommer, R. J. (2013): A developmental switch coupled to the evolution of plasticity acts through a sulfatase. Cell, 155, 922-933.

Rödelsperger, C. & Sommer, R. J. (2011): Computational archeology of the Pristionchus pacificus genome reveals evidence of horizontal gene transfers from insects. BMC Evol. Biol., 11: 239, DOI: 10.1186/1471-2148-11-239.

Rödelsperger, C., Streit, A., Sommer, R. J. (2013): Structure, function and evolution of the nematode genome. In: eLS. Chichester: John Wiley & Sons, Ltd., DOI: 10.1002/9780470015902.a0024603.

Rödelsperger, C., Neher, R. A., Weller, A., Eberhardt, G., Witte, H., Mayer, W., Dieterich, C. & Sommer, R. J. (2014): Characterization of genetic diversity in the nematode Pristionchus pacificus from population-scale resequencing data. Genetics, 196, 1153-1165.

Rödelsperger, C., Menden, K., Serobyan, V., Witte, H. & Baskaran, P. (2016): First insights into the nature and evolution of antisense transcription in nematodes. BMC Evol. Biol., 16: 165. DOI: 10.1186/s12862-016-0740-y

Witte, H., Moreno, E., Rödelsperger, C., Kim, J., Kim, J.-S., Streit A. & Sommer, R. J. (2015): Gene inactivation using the CRISPR/Cas9 system in the nematode Pristionchus pacificus. Dev Genes & Evol., 225, 55-62.

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