Examining the role of components of Slc11a1 (Nramp1) in the susceptibility of New Zealand sea lions (Phocarctos hookeri) to disease

PLoS One. 2015 Apr 14;10(4):e0122703. doi: 10.1371/journal.pone.0122703. eCollection 2015.

Abstract

The New Zealand sea lion (NZSL, Phocarctos hookeri) is a Threatened marine mammal with a restricted distribution and a small, declining, population size. The species is susceptible to bacterial pathogens, having suffered three mass mortality events since 1998. Understanding the genetic factors linked to this susceptibility is important in mitigating population decline. The gene solute carrier family 11 member a1 (Slc11a1) plays an important role in mammalian resistance or susceptibility to a wide range of bacterial pathogens. At present, Slc11a1 has not been characterised in many taxa, and despite its known roles in mediating the effects of infectious disease agents, has not been examined as a candidate gene in susceptibility or resistance in any wild population of conservation concern. Here we examine components of Slc11a1 in NZSLs and identify: i) a polymorphic nucleotide in the promoter region; ii) putative shared transcription factor binding motifs between canids and NZSLs; and iii) a conserved polymorphic microsatellite in the first intron of Slc11a1, which together suggest conservation of Slc11a1 gene structure in otariids. At the promoter polymorphism, we demonstrate a shift away from normal allele frequency distributions and an increased likelihood of death from infectious causes with one allelic variant. While this increased likelihood is not statistically significant, lack of significance is potentially due to the complexity of genetic susceptibility to disease in wild populations. Our preliminary data highlight the potential significance of this gene in disease resistance in wild populations; further exploration of Slc11a1 will aid the understanding of susceptibility to infection in mammalian species of conservation significance.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Infections / epidemiology
  • Bacterial Infections / genetics
  • Bacterial Infections / veterinary*
  • Base Sequence
  • Binding Sites
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / physiology*
  • Disease Outbreaks / veterinary
  • Disease Resistance / genetics
  • Dogs / genetics
  • Endangered Species
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Haplotypes / genetics
  • Immunity, Innate / genetics
  • Introns / genetics
  • Mammals / classification
  • Mammals / genetics
  • Microsatellite Repeats
  • Molecular Sequence Data
  • Phylogeny
  • Polymorphism, Genetic
  • Promoter Regions, Genetic / genetics
  • Sea Lions / classification
  • Sea Lions / genetics*
  • Sea Lions / immunology
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid
  • Species Specificity
  • Transcription Factors / metabolism

Substances

  • Cation Transport Proteins
  • Transcription Factors
  • natural resistance-associated macrophage protein 1

Grants and funding

Funding was provided by the University of Otago; subcontract to NJG from Landcare Research’s FRST OBI "Sustaining and Restoring Biodiversity" contract #C09X0503; and University of Otago Department of Anatomy PhD Scholarship to AJO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.