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The Journal of heredity2008; 99(5); 500-511; doi: 10.1093/jhered/esn029

Concerted evolution of vertebrate CCR2 and CCR5 genes and the origin of a recombinant equine CCR5/2 gene.

Abstract: Chemokine receptors (CCRs) play an essential role in the initiation of an innate immune host response. Several of these receptors have been shown to modulate the outcome of viral infections. The recent availability of complete genome sequences from a number of species provides a unique opportunity to analyze the evolution of the CCR genes. A phylogenetic analysis revealed that the CCR2 gene evolved in concert with the paralogous CCR5 gene, but not with another paralogous gene, CCR3, in the opossum, platypus, rabbit, guinea pig, cat, and rodent lineages. In addition, evidence of concerted evolution of the CCR2 and CCR5 genes was observed in chicken and lizard genomes. A unique CCR5/2 gene that originated by unequal crossing over between the CCR2 and CCR5 genes was detected in the domestic horse. The CCR2, CCR5, and CCR5/2 genes were mapped to ECA16q21 using fluorescent in situ hybridization (FISH). Single-nucleotide polymorphisms identified in the equine CCR5 gene and characterized within 5 horse breeds provide haplotype markers for future case/control studies investigating the genetic bases of horse susceptibility to infectious diseases.
Publication Date: 2008-05-22 PubMed ID: 18502735DOI: 10.1093/jhered/esn029Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

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The study examines the evolution of vertebrate Chemokine receptor (CCR) genes – CCR2 and CCR5, and the origin of a recombinant equine CCR5/2 gene. It reveals a concerted evolution between CCR2 and CCR5, and identifies unique genetic features in horses that contribute to their susceptibility or resistance to infectious diseases.

Evolution of CCR2 and CCR5 Genes

  • CCR2 and CCR5 genes are part of the chemokine receptor family, which plays a crucial role in triggering the body’s immune response. In particular, these genes can influence the outcome of viral infections.
  • The researchers carried out a phylogenetic analysis utilising the complete genome sequences of various species. They found that CCR2 evolved concurrently with CCR5, but not with the similarly grouped CCR3 gene. This evolution pattern was observed in several species, including opossum, platypus, rabbit, guinea pig, cat, and rodents.
  • This tendency for concerted evolution between CCR2 and CCR5 was also discovered in chicken and lizard genomes, reinforcing the close relational and functional association between these two paralogous genes.

Origin of Recombinant Equine CCR5/2 Gene

  • During the examination of the genome of the domestic horse, the researchers found a unique CCR5/2 gene, which was believed to have formed due to an unequal crossover event between the sequences of the CCR2 and CCR5 genes.
  • The existence of this unique CCR5/2 gene, coupled with the location of CCR2, CCR5, and CCR5/2 genes mapped to a specific region of the horse’s 16th chromosome (ECA16q21), hint at potential genetic factors that make horses susceptible to certain infectious diseases.

Future Implications of the Study

  • Single-nucleotide polymorphisms identified in the equine CCR5 gene were characterized in 5 horse breeds. These may be used as haplotype markers for future studies that aim to understand the genetic basis of horses’ susceptibility to infectious diseases.
  • This discovery could have important implications for equine healthcare and disease prevention, as it may pave the way for the development of gene-targeted treatments or prevention strategies.

Cite This Article

APA
Perelygin AA, Zharkikh AA, Astakhova NM, Lear TL, Brinton MA. (2008). Concerted evolution of vertebrate CCR2 and CCR5 genes and the origin of a recombinant equine CCR5/2 gene. J Hered, 99(5), 500-511. https://doi.org/10.1093/jhered/esn029

Publication

ISSN: 1465-7333
NlmUniqueID: 0375373
Country: United States
Language: English
Volume: 99
Issue: 5
Pages: 500-511

Researcher Affiliations

Perelygin, Andrey A
  • Department of Biology, Georgia State University, PO Box 4010, Atlanta, GA 30302, USA. aperelygin@gsu.edu
Zharkikh, Andrey A
    Astakhova, Natalia M
      Lear, Teri L
        Brinton, Margo A

          MeSH Terms

          • Animals
          • Base Sequence
          • Cats
          • Cattle
          • Chickens
          • Chromosome Mapping
          • DNA
          • Elephants
          • Equidae / classification
          • Equidae / genetics
          • Evolution, Molecular
          • Exons
          • Genotype
          • Humans
          • In Situ Hybridization, Fluorescence
          • Introns
          • Molecular Sequence Data
          • Phylogeny
          • Polymorphism, Single Nucleotide
          • Rabbits
          • Receptors, CCR2 / genetics
          • Receptors, CCR5 / genetics
          • Recombination, Genetic
          • Swine
          • Synteny
          • Vertebrates / genetics

          Grant Funding

          • R01 CI000216 / NCPDCID CDC HHS
          • CI000216 / NCPDCID CDC HHS

          Citations

          This article has been cited 6 times.
          1. Fernandes AP, Águeda-Pinto A, Pinheiro A, Rebelo H, Esteves PJ. Evolution of CCR5 and CCR2 Genes in Bats Showed Multiple Independent Gene Conversion Events.. Viruses 2022 Jan 18;14(2).
            doi: 10.3390/v14020169pubmed: 35215768google scholar: lookup
          2. Neves F, Abrantes J, Lopes AM, Fusinatto LA, Magalhães MJ, van der Loo W, Esteves PJ. Evolution of CCL16 in Glires (Rodentia and Lagomorpha) shows an unusual random pseudogenization pattern.. BMC Evol Biol 2019 Feb 20;19(1):59.
            doi: 10.1186/s12862-019-1390-7pubmed: 30786851google scholar: lookup
          3. Hoover KC. Intragenus (Homo) variation in a chemokine receptor gene (CCR5).. PLoS One 2018;13(10):e0204989.
            doi: 10.1371/journal.pone.0204989pubmed: 30278065google scholar: lookup
          4. Chen Y, Zhou S, Jiang Z, Wang X, Liu Y. Chemokine receptor CXCR3 in turbot (Scophthalmus maximus): cloning, characterization and its responses to lipopolysaccharide.. Fish Physiol Biochem 2016 Apr;42(2):659-71.
            doi: 10.1007/s10695-015-0167-1pubmed: 26585996google scholar: lookup
          5. Widdison S, Siddiqui N, Easton V, Lawrence F, Ashley G, Werling D, Watson M, Coffey TJ. The bovine chemokine receptors and their mRNA abundance in mononuclear phagocytes.. BMC Genomics 2010 Jul 19;11:439.
            doi: 10.1186/1471-2164-11-439pubmed: 20642824google scholar: lookup
          6. Metzger KJ, Thomas MA. Evidence of positive selection at codon sites localized in extracellular domains of mammalian CC motif chemokine receptor proteins.. BMC Evol Biol 2010 May 10;10:139.
            doi: 10.1186/1471-2148-10-139pubmed: 20459756google scholar: lookup