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Balancing selection on the complement system of a wild rodent

Nandakumar, Mridula LU orcid ; Lundberg, Max LU ; Carlsson, Fredric LU and Råberg, Lars LU (2023) In BMC Ecology and Evolution 23(1).
Abstract

Background: Selection pressure exerted by pathogens can influence patterns of genetic diversity in the host. In the immune system especially, numerous genes encode proteins involved in antagonistic interactions with pathogens, paving the way for coevolution that results in increased genetic diversity as a consequence of balancing selection. The complement system is a key component of innate immunity. Many complement proteins interact directly with pathogens, either by recognising pathogen molecules for complement activation, or by serving as targets of pathogen immune evasion mechanisms. Complement genes can therefore be expected to be important targets of pathogen-mediated balancing selection, but analyses of such selection on this... (More)

Background: Selection pressure exerted by pathogens can influence patterns of genetic diversity in the host. In the immune system especially, numerous genes encode proteins involved in antagonistic interactions with pathogens, paving the way for coevolution that results in increased genetic diversity as a consequence of balancing selection. The complement system is a key component of innate immunity. Many complement proteins interact directly with pathogens, either by recognising pathogen molecules for complement activation, or by serving as targets of pathogen immune evasion mechanisms. Complement genes can therefore be expected to be important targets of pathogen-mediated balancing selection, but analyses of such selection on this part of the immune system have been limited. Results: Using a population sample of whole-genome resequencing data from wild bank voles (n = 31), we estimated the extent of genetic diversity and tested for signatures of balancing selection in multiple complement genes (n = 44). Complement genes showed higher values of standardised β (a statistic expected to be high under balancing selection) than the genome-wide average of protein coding genes. One complement gene, FCNA, a pattern recognition molecule that interacts directly with pathogens, was found to have a signature of balancing selection, as indicated by the Hudson-Kreitman-Aguadé test (HKA) test. Scans for localised signatures of balancing selection in this gene indicated that the target of balancing selection was found in exonic regions involved in ligand binding. Conclusion: The present study adds to the growing evidence that balancing selection may be an important evolutionary force on components of the innate immune system. The identified target in the complement system typifies the expectation that balancing selection acts on genes encoding proteins involved in direct interactions with pathogens.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Balancing selection, Bank voles, Complement system, Myodes glareolus, Pathogen-mediated selection
in
BMC Ecology and Evolution
volume
23
issue
1
article number
21
publisher
Springer
external identifiers
  • pmid:37231383
  • scopus:85160262534
ISSN
2730-7182
DOI
10.1186/s12862-023-02122-0
language
English
LU publication?
yes
id
eaf14d66-aa6d-4039-acf3-0ec4fec5a042
date added to LUP
2023-08-15 11:56:23
date last changed
2024-04-20 00:36:13
@article{eaf14d66-aa6d-4039-acf3-0ec4fec5a042,
  abstract     = {{<p>Background: Selection pressure exerted by pathogens can influence patterns of genetic diversity in the host. In the immune system especially, numerous genes encode proteins involved in antagonistic interactions with pathogens, paving the way for coevolution that results in increased genetic diversity as a consequence of balancing selection. The complement system is a key component of innate immunity. Many complement proteins interact directly with pathogens, either by recognising pathogen molecules for complement activation, or by serving as targets of pathogen immune evasion mechanisms. Complement genes can therefore be expected to be important targets of pathogen-mediated balancing selection, but analyses of such selection on this part of the immune system have been limited. Results: Using a population sample of whole-genome resequencing data from wild bank voles (n = 31), we estimated the extent of genetic diversity and tested for signatures of balancing selection in multiple complement genes (n = 44). Complement genes showed higher values of standardised β (a statistic expected to be high under balancing selection) than the genome-wide average of protein coding genes. One complement gene, FCNA, a pattern recognition molecule that interacts directly with pathogens, was found to have a signature of balancing selection, as indicated by the Hudson-Kreitman-Aguadé test (HKA) test. Scans for localised signatures of balancing selection in this gene indicated that the target of balancing selection was found in exonic regions involved in ligand binding. Conclusion: The present study adds to the growing evidence that balancing selection may be an important evolutionary force on components of the innate immune system. The identified target in the complement system typifies the expectation that balancing selection acts on genes encoding proteins involved in direct interactions with pathogens.</p>}},
  author       = {{Nandakumar, Mridula and Lundberg, Max and Carlsson, Fredric and Råberg, Lars}},
  issn         = {{2730-7182}},
  keywords     = {{Balancing selection; Bank voles; Complement system; Myodes glareolus; Pathogen-mediated selection}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Springer}},
  series       = {{BMC Ecology and Evolution}},
  title        = {{Balancing selection on the complement system of a wild rodent}},
  url          = {{http://dx.doi.org/10.1186/s12862-023-02122-0}},
  doi          = {{10.1186/s12862-023-02122-0}},
  volume       = {{23}},
  year         = {{2023}},
}