Adaptive evolution of immune gene families: origin, diversification and diversity of the NLR genes in zebrafish

LE 546/9-1, WI 3081/5-1

The co-evolutionary arms race between hosts and their pathogens is the major driver of the rapid evolutionary dynamics of the host immune repertoire. A key aspect in this process is the high diversity of the components of the host's immune system. In this project we will focus on the mechanisms behind this fast diversification, and study the evolution of the so-called NLR gene family in natural populations of zebrafish, Danio rerio.This gene family, as well as the experimental organism, are well suited for the analysis of the host's race for ecological adaptation. Danio rerio is an established model organism in genetic and immunological research. The recent release of a new high-quality genome assembly provides a robust basis for evolutionary genomics. The genes targeted in this project constitute an extremely large, very recently expanded, family of about 400 members in zebrafish.To understand the nature of the evolutionary and adaptive forces which have shaped this gene family and the encoded proteins we will collect large scale genomic sequence data from different wild populations with different ecological conditions (e.g., pristine vs. polluted waters) and analyse these data with publicly available as well as with customized and own-developed population genetic methods.The project will dissect the dynamics of recent adaptation events, and the mechanisms that have shaped the diversification of this gene family in populations exposed to different environments.In particular, we will target the dense NLR-cluster on chromosome 4 of Danio rerio. For these genes and their upstream regulatory regions we will determine mutation frequency spectra, measure evolutionary rates and selective constraints across genes and encoded proteins.We expect to identify a set of evolutionary hotspots, which have been subject to environmentally triggered adaptation. These will be prime candidates for future functional studies in follow-up transcriptomics (of the host) and meta-genomics (of the environment) experiments.

Publications

• Jaanus Suurväli, Andrew R Whiteley, Yichen Zheng, Karim Gharbi, Maria Leptin, Thomas Wiehe (2019) The laboratory domestication of zebrafish: from diverse populations to inbred substrains. Molecular Biology and Evolution, msz289. DOI: 10.1093/molbev/msz289
  
  
• Philipp H. Schiffer, ... , Thomas Wiehe, Mark Blaxter (2019) Signatures of the evolution of parthenogenesis and cryptobiosis in the genomes of panagrolaimid nematodes. iScience, 22: 587-602. DOI: 10.1016/j.isci.2019.10.039
  
  
• Kerstin Howe, Philipp H. Schiffer, Julia Zielinski, Thomas Wiehe, Gavin K. Laird, John C. Marioni, Onuralp Soylemez, Fyodor Kondrashov, Maria Leptin (2016) Structure and evolutionary history of a large family of NLR proteins in the zebrafish. Open Biol. 6: 160009. DOI: 10.1098/rsob.160009
  
  
• Philipp H. Schiffer, Jan Gravemeyer, Martina Rauscher and Thomas Wiehe (2016) Ultra Large Gene Families: A Matter of Adaptation or Genomic Parasites? Life 6: 32. DOI:10.3390/life6030032