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Balancing selection in Pattern Recognition Receptor signalling pathways is associated with gene function and pleiotropy in a wild rodent

Lundberg, Max LU ; Zhong, Xiuqin LU ; Konrad, Anna ; Olsen, Remi André and Råberg, Lars LU (2020) In Molecular Ecology 29(11). p.1990-2003
Abstract

Pathogen-mediated balancing selection is commonly considered to play an important role in the maintenance of genetic diversity, in particular in immune genes. However, the factors that may influence which immune genes are the targets of such selection are largely unknown. To address this, here we focus on Pattern Recognition Receptor (PRR) signalling pathways, which play a key role in innate immunity. We used whole-genome resequencing data from a population of bank voles (Myodes glareolus) to test for associations between balancing selection, pleiotropy and gene function in a set of 123 PRR signalling pathway genes. To investigate the effect of gene function, we compared genes encoding (a) receptors for microbial ligands versus... (More)

Pathogen-mediated balancing selection is commonly considered to play an important role in the maintenance of genetic diversity, in particular in immune genes. However, the factors that may influence which immune genes are the targets of such selection are largely unknown. To address this, here we focus on Pattern Recognition Receptor (PRR) signalling pathways, which play a key role in innate immunity. We used whole-genome resequencing data from a population of bank voles (Myodes glareolus) to test for associations between balancing selection, pleiotropy and gene function in a set of 123 PRR signalling pathway genes. To investigate the effect of gene function, we compared genes encoding (a) receptors for microbial ligands versus downstream signalling proteins, and (b) receptors recognizing components of microbial cell walls, flagella and capsids versus receptors recognizing features of microbial nucleic acids. Analyses based on the nucleotide diversity of full coding sequences showed that balancing selection primarily targeted receptor genes with a low degree of pleiotropy. Moreover, genes encoding receptors recognizing components of microbial cell walls etc. were more important targets of balancing selection than receptors recognizing nucleic acids. Tests for localized signatures of balancing selection in coding and noncoding sequences showed that such signatures were mostly located in introns, and more evenly distributed among different functional categories of PRR pathway genes. The finding that signatures of balancing selection in full coding sequences primarily occur in receptor genes, in particular those encoding receptors for components of microbial cell walls etc., is consistent with the idea that coevolution between hosts and pathogens is an important cause of balancing selection on immune genes.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
balancing selection, gene conversion, host–pathogen coevolution, innate immune genes, protein–protein interactions
in
Molecular Ecology
volume
29
issue
11
pages
14 pages
publisher
Wiley-Blackwell
external identifiers
  • pmid:32374503
  • scopus:85085561581
ISSN
0962-1083
DOI
10.1111/mec.15459
language
English
LU publication?
yes
id
35889467-b259-40c3-a535-791897027b78
date added to LUP
2020-06-26 13:44:32
date last changed
2024-07-10 17:44:24
@article{35889467-b259-40c3-a535-791897027b78,
  abstract     = {{<p>Pathogen-mediated balancing selection is commonly considered to play an important role in the maintenance of genetic diversity, in particular in immune genes. However, the factors that may influence which immune genes are the targets of such selection are largely unknown. To address this, here we focus on Pattern Recognition Receptor (PRR) signalling pathways, which play a key role in innate immunity. We used whole-genome resequencing data from a population of bank voles (Myodes glareolus) to test for associations between balancing selection, pleiotropy and gene function in a set of 123 PRR signalling pathway genes. To investigate the effect of gene function, we compared genes encoding (a) receptors for microbial ligands versus downstream signalling proteins, and (b) receptors recognizing components of microbial cell walls, flagella and capsids versus receptors recognizing features of microbial nucleic acids. Analyses based on the nucleotide diversity of full coding sequences showed that balancing selection primarily targeted receptor genes with a low degree of pleiotropy. Moreover, genes encoding receptors recognizing components of microbial cell walls etc. were more important targets of balancing selection than receptors recognizing nucleic acids. Tests for localized signatures of balancing selection in coding and noncoding sequences showed that such signatures were mostly located in introns, and more evenly distributed among different functional categories of PRR pathway genes. The finding that signatures of balancing selection in full coding sequences primarily occur in receptor genes, in particular those encoding receptors for components of microbial cell walls etc., is consistent with the idea that coevolution between hosts and pathogens is an important cause of balancing selection on immune genes.</p>}},
  author       = {{Lundberg, Max and Zhong, Xiuqin and Konrad, Anna and Olsen, Remi André and Råberg, Lars}},
  issn         = {{0962-1083}},
  keywords     = {{balancing selection; gene conversion; host–pathogen coevolution; innate immune genes; protein–protein interactions}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1990--2003}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Molecular Ecology}},
  title        = {{Balancing selection in Pattern Recognition Receptor signalling pathways is associated with gene function and pleiotropy in a wild rodent}},
  url          = {{http://dx.doi.org/10.1111/mec.15459}},
  doi          = {{10.1111/mec.15459}},
  volume       = {{29}},
  year         = {{2020}},
}