High MHC diversity maintained by balancing selection in an otherwise genetically monomorphic mammal

Abstract

The San Nicolas Island fox (Urocyon littoralis dickeyi) is genetically the most monomorphic sexually reproducing animal population yet reported and has no variation in hypervariable genetic markers. Such low levels of variation imply lower resistance to pathogens, reduced fitness, and problems in distinguishing kin from non-kin. In vertebrates, the MHC contains genes that influence disease resistance and kin recognition and may be under intense balancing selection in some populations. Hence, genetic variation at the MHC might persist despite the extreme monomorphism shown by neutral markers. We examine variation of five loci within the MHC of San Nicolas Island foxes and find remarkably high levels of variation. Further, we show by simulation that genetic monomorphism at neutral loci and high MHC variation could arise only through an extreme population bottleneck of <10 individuals, approximately 10-20 generations ago, accompanied by unprecedented selection coefficients of >0.5 on MHC loci. These results support the importance of balancing selection as a mechanism to maintain variation in natural populations and expose the difficulty of using neutral markers as surrogates for variation in fitness-related loci.

Fig. 1.

Location of the six southern California Channel Islands where island foxes are found. Dotted line indicates hypothesized colonization routes (3). Approximate colonization times in years before present (ybp) based on the archeological record are provided (4).

Fig. 2.

The relationship between heterozygosity and the selection coefficient (s) as determined by demographic simulations for the IAM (DRB, μ = 10^-6) and the SMM (FH2202, CFA12-4, and CFA12-13, μ = 10^-2, 10^-3, and 10^-4). Mean heterozygosity and SE are reported for 500 simulations (see Supporting Text).