Extensive variation at MHC DRB in the New Zealand sea lion (Phocarctos hookeri) provides evidence for balancing selection

Abstract

Marine mammals are often reported to possess reduced variation of major histocompatibility complex (MHC) genes compared with their terrestrial counterparts. We evaluated diversity at two MHC class II B genes, DQB and DRB, in the New Zealand sea lion (Phocarctos hookeri, NZSL) a species that has suffered high mortality owing to bacterial epizootics, using Sanger sequencing and haplotype reconstruction, together with next-generation sequencing. Despite this species' prolonged history of small population size and highly restricted distribution, we demonstrate extensive diversity at MHC DRB with 26 alleles, whereas MHC DQB is dimorphic. We identify four DRB codons, predicted to be involved in antigen binding, that are evolving under adaptive evolution. Our data suggest diversity at DRB may be maintained by balancing selection, consistent with the role of this locus as an antigen-binding region and the species' recent history of mass mortality during a series of bacterial epizootics. Phylogenetic analyses of DQB and DRB sequences from pinnipeds and other carnivores revealed significant allelic diversity, but little phylogenetic depth or structure among pinniped alleles; thus, we could neither confirm nor refute the possibility of trans-species polymorphism in this group. The phylogenetic pattern observed however, suggests some significant evolutionary constraint on these loci in the recent past, with the pattern consistent with that expected following an epizootic event. These data may help further elucidate some of the genetic factors underlying the unusually high susceptibility to bacterial infection of the threatened NZSL, and help us to better understand the extent and pattern of MHC diversity in pinnipeds.

Heterozygote advantage at MHC DRB may influence response to infectious disease epizootics

“…We have previously shown in the NZSL that variation is limited at DQB (Osborne et al . ), in keeping with the earlier finding of Lento et al . (Lento et al .…”

“…Microsatellite genotyping at 17 loci was undertaken on all the pups in this study and has been described elsewhere (Osborne ; Osborne et al . ). The R program GENHET (Coulon ) was used to calculate five different measures of microsatellite heterozygosity or homozygosity, as described in Coulon () [Mean PHt, proportion of heterozygous loci in an individual; Hs_obs, standardized heterozygosity based on the mean observed heterozygosity (Coltman et al .…”

Is management limiting the recovery of the New Zealand sea lion Phocarctos hookeri?

“…The historical N e for the NZ sea lion was 9,563 or 14,694 (depending on the H e value used), which resulted in a historical census population size (N C ) in the range of 21,251-133,581 individuals (depending on the N e /N C ratio) N current is the current estimate of population size based on the IUCN redlist and N e :N current is the ratio of effective population size to the IUCN estimate, which provides information on a possible otariid-specific ratio (mean 0.14 ± 0.18 SD, all otariids, excluding the NZ sea lion) a Osborne et al (2013) b Acevedo-Whitehouse et al (2009) c See Table 1 in Robertson and Chilvers (2011) d See Table 3 in Curtis et al (2011) Polar Biol at some point in the past ( Table 1). Comparison of the historical N C values with current estimated population sizes (N current ) indicated that three species (NZ sea lion, Australian sea lion Neophoca cinerea and Galápagos sea lion Zalophus wollebaeki) have not attained the expected historical N C (i.e.…”

“…One estimate (0.72) is based on 39 individual pups from a single breeding season at Sandy Bay breeding colony in the Auckland Islands (AcevedoWhitehouse et al 2009). The other estimate (0.66) is based on 1,351 individuals sampled over seven breeding seasons and includes live and dead pups of the year, as well as mothers and breeding male sea lions (potential fathers) from three breeding colonies on the Auckland Islands (Osborne et al 2013). When inbred individuals or close relatives are included in a sample (as is the case for the large sample size), H e has a downward bias (Weir 1989;DeGiorgio and Rosenberg 2009), which might account for the difference between the two H e values (as could sampling bias associated with a small sample size) (Fig.…”

Short Communication Sequence variation and gene duplication at the MHC DRB loci of the spotted seal Phoca largha

“…In MHC class II genes, the DRB regions exhibit the most elaborate polymorphisms, and these have been extensively characterized in marine mammals, due to their importance in immunological research (Bowen et al, 2004;Osborne et al, 2013). In this study, we examined the loci within the DRB region, with emphasis on the second exon of DRB.…”