Gene dynamics of toll-like receptor 4 through a population bottleneck in an insular population of water voles (Arvicola amphibius)

Abstract

Understanding the extent to which diversity at immunologically important genes is reduced by demographic perturbations such as population bottlenecks, and the resulting consequences this has on individual fitness, is of fundamental importance for the effective management of genetic resources in natural populations. Toll-like receptors are key immunological genes with well-established links to fitness. Here, levels of allelic diversity and heterozygosity at the toll-like receptor 4 locus (Tlr4) were characterised across 280 water voles (Arvicola amphibius) from an isolated, island population in north west Scotland that went through a severe population bottleneck between 2004 and 2006 that eroded neutral microsatellite variation. Two functional Tlr4 alleles were resolved prior to the population crash at frequencies close to parity and an excess of heterozygote genotypes relative to Hardy-Weinberg expectations. Through the population bottleneck both alleles were retained with genotype frequencies conforming to Hardy-Weinberg expectations. Tlr4 genotype was significantly associated with gamasid mite, flea (Megabothris walkeri) and sheep tick larva (Ixodes ricinus) burdens among individuals, suggesting a mechanism through which parasite mediated selection could affect Tlr4 diversity. The results are examined with recourse to the extent that they are consistent with the effects of genetic drift and balancing selection, and their significance is discussed in relation to identifying target genes that assay ecological and adaptively meaningful genetic variation in a conservation context.

Signatures of balancing selection in toll-like receptor (TLRs) genes – novel insights from a free-living rodent

“…Clinical studies have shown that polymorphism within TLR genes, particularly in the part of the molecule interacting with PAMP, affects susceptibility to diseases in humans – for instance, a single nucleotide polymorphism (SNP) in the TLR2 gene has been attributed to susceptibility to tuberculosis, cytomeglaovirus, and borreliosis, whereas SNPs associated with susceptibility to hepatitis C virus have been identified in TLR7 (see the work reviewed in 6 ). Associations between TLR variants and susceptibility have also recently been found in TLR2 and TLR4 4 , 7 in free living species.…”

Digging for gold nuggets: uncovering novel candidate genes for variation in gastrointestinal nematode burden in a wild bird species

“…The genetic basis of parasite susceptibility has been notoriously difficult to uncover (Wilfert & Schmid‐Hempel, ), although some insight has been gained through bottom‐up candidate gene approaches involving MHC (e.g. Oliver et al ., ; Oppelt et al ., ; Sin et al ., ), interferon‐gamma (Coltman et al ., ; Stear et al ., ), Toll‐like receptors (Downing et al ., ; Gavan et al ., ) and cytokines (Luikart et al ., ; Downing et al ., ; Turner et al ., ). Landscape‐scale application of novel top‐down candidate genes for parasite susceptibility in Daphnia revealed differential patterns of selection at these genes among populations in different stress environments, but no conclusive associations between allele frequencies and parasite prevalence were found (Orsini et al ., ).…”

“…These effects may be underpinned by substantial numbers of genes with small individual effect sizes (Wilfert & Schmid‐Hempel, ; Rockman, ). Although heritability of parasite susceptibility and tolerance is well documented (Gauly & Erhardt, ; Stear et al ., ; Mazé‐Guilmo et al ., ) and a range of bottom‐up candidate immune system genes, such as the MHC (Oliver et al ., ; Oppelt et al ., ; Sin et al ., ), interferon‐gamma (Coltman et al ., ; Stear et al ., ), Toll‐like receptors (Downing et al ., ; Gavan et al ., ) and cytokines (Luikart et al ., ; Downing et al ., ; Turner et al ., ), have provided some insight, identification of novel top‐down candidate genes for parasite infection in animals beyond immune system genes has proved to be a major challenge. For example, no conclusive associations between candidate gene allele frequencies and parasite prevalence were found in Daphnia (Orsini et al ., ) and Soay sheep populations (Brown et al ., ), despite employing transcriptomic assays for gene discovery (Orsini et al ., ; Pemberton et al ., ).…”

Adaptive landscape genetics and malaria across divergent island bird populations

“…However, a greater proportion of phenotypic variance in malaria response has been attributed to non-MHC genes (Jepson et al, 1997). Within the innate immune system (a first line of defense against infection), Toll-like receptors (TLRs) are a family of pattern-recognition receptors which have been linked to malaria resistance (Ferwerda et al, 2007;Mockenhaupt et al, 2006), and show evidence of pathogen-mediated balancing selection (Ferrer-Admetlla et al, 2008;Fisher et al, 2011;Gavan, Oliver, Douglas, & Piertney, 2015). TLRs therefore represent important candidates for investigating the role of pathogens in maintaining host genetic variation.…”