Beyond neutral loci: Examining immune gene variation in tigers (Panthera tigris)

Abstract

Isolated and inbred populations are at a higher risk to extinction due to the loss of genetic diversity. Carnivores are particularly susceptible to isolation due to their ecological requirements. Studies generally assess genetic vulnerability using neutral loci, but these may not accurately reflect a population's adaptive potential. In contrast, diversity at loci putatively involved in fitness and hence survival, such as immune genes, could be a better proxy for future survival. Research on immune genes has traditionally focused on the MHC loci. We extend this investigation to five families of non-MHC immune genes -Tumor Necrosis Factor, Interleukin, Toll-like Receptor, Leukocyte Immunoglobulin Receptors, and Chemokine - involved in adaptive and innate immunity in tigers which exemplifies an endangered carnivore. We compare immune gene diversity to neutral diversity across the genome using whole genome resequencing data from 107 tigers, representing all extant subspecies and populations of different demographic histories. Our analysis reveals that immune receptor genes (mean nucleotide diversity: 0.0019) show high nucleotide diversity compared to neutral loci (0.0008) and immune signalling genes (0.0004) indicating past positive selection. Heterozygosity at the three classes of loci suggest that most immune genes are evolving neutrally. We confirm that small, isolated populations have lower nucleotide diversity and heterozygosity at both neutral and immune loci compared to large and connected populations. Additionally, genetic differentiation and deleterious mutation load correspond to known signatures from inbreeding and recent bottlenecks. Despite low neutral and immunogenetic diversity in small populations, some loci retain polymorphisms, irrespective of adaptive or innate immune functions. We conclude that drift is the predominant evolutionary force in bottlenecked populations even at adaptive loci.