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Positive Selection on Mammalian Immune Genes - Effects of Gene Function and Selective Constraint

Nandakumar, Mridula LU orcid ; Lundberg, Max LU ; Carlsson, Fredric LU orcid and Råberg, Lars LU (2025) In Molecular biology and evolution 42(1).
Abstract

Genome-wide analyses of various taxa have repeatedly shown that immune genes are important targets of positive selection. However, little is known about what factors determine which immune genes are under positive selection. To address this question, we here focus on the mammalian immune system and investigate the importance of gene function and other factors such as gene expression, protein-protein interactions, and overall selective constraint as determinants of positive selection. We compiled a list of >1,100 immune genes that were divided into six functional categories and analyzed using data from rodents. Genes encoding proteins that are in direct interactions with pathogens, such as pattern recognition receptors (PRRs), are... (More)

Genome-wide analyses of various taxa have repeatedly shown that immune genes are important targets of positive selection. However, little is known about what factors determine which immune genes are under positive selection. To address this question, we here focus on the mammalian immune system and investigate the importance of gene function and other factors such as gene expression, protein-protein interactions, and overall selective constraint as determinants of positive selection. We compiled a list of >1,100 immune genes that were divided into six functional categories and analyzed using data from rodents. Genes encoding proteins that are in direct interactions with pathogens, such as pattern recognition receptors (PRRs), are often expected to be key targets of positive selection. We found that categories containing cytokines, cytokine receptors, and other cell surface proteins involved in, for example, cell-cell interactions were at least as important targets as PRRs, with three times higher rate of positive selection than nonimmune genes. The higher rate of positive selection on cytokines and cell surface proteins was partly an effect of these categories having lower selective constraint. Nonetheless, cytokines had a higher rate of positive selection than nonimmune genes even at a given level of selective constraint, indicating that gene function per se can also be a determinant of positive selection. These results have broad implications for understanding the causes of positive selection on immune genes, specifically the relative importance of host-pathogen coevolution versus other processes.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
coevolution, gene expression tissue specificity, molecular evolution, pathogen-mediated selection, pN/pS, Rodentia
in
Molecular biology and evolution
volume
42
issue
1
article number
msaf016
publisher
Oxford University Press
external identifiers
  • pmid:39834162
  • scopus:85217030820
ISSN
0737-4038
DOI
10.1093/molbev/msaf016
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s). Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.
id
ac8e4d94-fbfd-47a7-a389-7efeb012bbaf
date added to LUP
2025-02-21 12:51:34
date last changed
2025-07-12 00:39:51
@article{ac8e4d94-fbfd-47a7-a389-7efeb012bbaf,
  abstract     = {{<p>Genome-wide analyses of various taxa have repeatedly shown that immune genes are important targets of positive selection. However, little is known about what factors determine which immune genes are under positive selection. To address this question, we here focus on the mammalian immune system and investigate the importance of gene function and other factors such as gene expression, protein-protein interactions, and overall selective constraint as determinants of positive selection. We compiled a list of &gt;1,100 immune genes that were divided into six functional categories and analyzed using data from rodents. Genes encoding proteins that are in direct interactions with pathogens, such as pattern recognition receptors (PRRs), are often expected to be key targets of positive selection. We found that categories containing cytokines, cytokine receptors, and other cell surface proteins involved in, for example, cell-cell interactions were at least as important targets as PRRs, with three times higher rate of positive selection than nonimmune genes. The higher rate of positive selection on cytokines and cell surface proteins was partly an effect of these categories having lower selective constraint. Nonetheless, cytokines had a higher rate of positive selection than nonimmune genes even at a given level of selective constraint, indicating that gene function per se can also be a determinant of positive selection. These results have broad implications for understanding the causes of positive selection on immune genes, specifically the relative importance of host-pathogen coevolution versus other processes.</p>}},
  author       = {{Nandakumar, Mridula and Lundberg, Max and Carlsson, Fredric and Råberg, Lars}},
  issn         = {{0737-4038}},
  keywords     = {{coevolution; gene expression tissue specificity; molecular evolution; pathogen-mediated selection; pN/pS; Rodentia}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  publisher    = {{Oxford University Press}},
  series       = {{Molecular biology and evolution}},
  title        = {{Positive Selection on Mammalian Immune Genes - Effects of Gene Function and Selective Constraint}},
  url          = {{http://dx.doi.org/10.1093/molbev/msaf016}},
  doi          = {{10.1093/molbev/msaf016}},
  volume       = {{42}},
  year         = {{2025}},
}