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Major Histocompatibility Complex Class II Variation in Bottlenose Dolphin from Adriatic Sea: Inferences About the Extent of Balancing Selection

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Major Histocompatibility Complex Class II Variation in Bottlenose Dolphin from Adriatic Sea: Inferences About the Extent of Balancing Selection Mar Biol (2014) 161:2407–2422 DOI 10.1007/s00227-014-2515-6 ORIGINAL PAPER Major histocompatibility complex class II variation in bottlenose dolphin from Adriatic Sea: inferences about the extent of balancing selection Haidi Arbanasic´ · Martina Đuras · Martina Podnar · Tomislav Gomercˇic´ · Snježana C´urkovic´ · Ana Galov Received: 20 December 2013 / Accepted: 31 July 2014 / Published online: 14 August 2014 © Springer-Verlag Berlin Heidelberg 2014 Abstract The bottlenose dolphin (Tursiops truncatus) synonymous substitution rates suggests that positive selec- is the most common cetacean species worldwide and the tion acts at both highly variable loci. Phylogenetic analy- only marine mammal species resident in the Croatian part ses revealed trans-species polymorphism at the DQB locus, of the Adriatic Sea. To gain insight into genetic diversity strongly indicating the influence of balancing selection in of bottlenose dolphins at adaptively important loci relevant the long term. In fact, the balancing selection observed in to conservation, we analysed the polymorphism of major bottlenose dolphins is higher than that reported for most histocompatibility complex (MHC) genes, which play a other cetaceans and comparable to that seen in terrestrial key role in pathogen confrontation and clearance. Specifi- mammals. cally, we examined the diversity of MHC class II DRA, DQA and DQB alleles in 50 bottlenose dolphins from the Adriatic Sea collected between 1997 and 2011 and in 12 Introduction animals from other Mediterranean locations. Notable vari- ation in DQA, DQB and three-locus haplotypes was found, The bottlenose dolphin (Tursiops truncatus) is the most with all 10 DQA and 12 DQB alleles encoding unique pro- abundant cetacean species; it inhabits primarily coastal tein products. Analysis of the ratio of non-synonymous to and inshore regions of warm and temperate seas around the world (Jefferson et al. 1993). Although the species can Communicated by T. Reusch. migrate long distances, analyses based on mitochondrial DNA and microsatellite loci showed genetic differentiation Electronic supplementary material The online version of this among dolphin populations both across its worldwide range article (doi:10.1007/s00227-014-2515-6) contains supplementary (Natoli et al. 2004) and on a regional geographic scale, e.g. material, which is available to authorized users. along a contiguous distributional range from the Black H. Arbanasic´ · A. Galov (*) Sea to the eastern North Atlantic (Natoli et al. 2005). The Department of Biology, Faculty of Science, University of Zagreb, latter study revealed that population boundaries coincide Rooseveltov trg 6, 10000 Zagreb, Croatia with transitions between habitat regions (e.g. the strong- e-mail: [email protected] est boundary is separating the Mediterranean and the Black M. Đuras · S. C´urkovic´ Seas), implying that bottlenose dolphin populations adapt Department of Anatomy, Histology and Embryology, Faculty to local environments leading to the observed regional pop- of Veterinary Medicine, University of Zagreb, Heinzelova 55, ulation structure. The results of Sharir et al. (2011), who 10000 Zagreb, Croatia found unique morphological characteristics of bottlenose M. Podnar dolphins from the easternmost region of the Mediterranean Croatian Natural History Museum, Demetrova 1, 10000 Zagreb, (Levant) to differ from those of western Mediterranean Croatia Seas, contribute to the local adaptation hypothesis. The bottlenose dolphin is the only resident marine mam- T. Gomercˇic´ Department of Biology, Faculty of Veterinary Medicine, mal species in the Croatian part of the Adriatic Sea, which University of Zagreb, Heinzelova 55, 10000 Zagreb, Croatia forms a semi-enclosed basin in the northern Mediterranean 1 3 2408 Mar Biol (2014) 161:2407–2422 (Bearzi et al. 2004; Đuras Gomercˇic´ et al. 2009). Popula- forms may be operating simultaneously to maintain MHC tion size was drastically reduced as a result of an inten- polymorphism. sive eradication campaign in the 1950s when culling was MHC genes have been used as indicators of evolutionary promoted as a means of mitigating conflict with fisheries and adaptive potential of populations and species in various (Bearzi et al. 2004), which may have induced a genetic bot- studies of population genetics, evolution, molecular ecol- tleneck effect, though definitive evidence for this is lacking ogy and conservation genetics. In marine mammals, the lev- (Galov et al. 2011). Area census surveys in 1998 estimated els of MHC polymorphism are unclear. On one hand, studies the total number of bottlenose dolphins in the Croatian have revealed high MHC diversity in grey seal (Halichoerus part of the Adriatic Sea at 218 individuals (Gomercˇic´ et al. grypus) (Cammen et al. 2011), California sea lion (Zalophus 2002). Today, the bottlenose dolphin is considered endan- californianus) (Bowen et al. 2006), baleen whales (Mysti- gered and is protected under Croatian law. Microsatellite ceti) (Baker et al. 2006) and finless porpoise (Neophocaena analysis did not indicate reduction of genetic diversity, phocaenoides) (Xu et al. 2007). On the other hand, studies implying that the Adriatic dolphins are not isolated and have reported low MHC diversity in fin whale (Balaenoptera may be part of a larger eastern Mediterranean population physalus) (Nigenda-Morales et al. 2008), sei whale (Balae- (Galov et al. 2011), which was inferred by Natoli et al. noptera borealis) (Trowsdale et al. 1989), beluga (Delphi- (2005). However, data on the fine-scale genetic structure napterus leucas) (Murray et al. 1995), narwhal (Monodon of the eastern Mediterranean bottlenose dolphin population monoceros) (Murray and White 1998) and vaquita (Phocoena are still missing. sinus) (Munguía-Vega et al. 2007). The low MHC polymor- Genetic studies on wild populations are mostly per- phism in these marine species has been attributed to the low formed on neutral makers which are informative regarding prevalence of infectious disease in the marine environment, population history or phylogenetic reconstructions. Never- since parasites and pathogens are thought to be the primary theless, if we are interested in adaptively important genetic agents selecting for MHC diversity (Trowsdale et al. 1989; diversity and selective processes that involve the interaction Slade 1992). Whatever its cause, this lower MHC polymor- of individuals with their environment, the best candidate phism has led researchers to hypothesise that balancing selec- genes for analysis are the genes of the major histocompat- tion on MHC loci is weaker in marine mammals than in terres- ibility complex (MHC) (Sommer 2005; Bernatchez and trial mammals. These inconsistent results about MHC genetic Landry 2003). MHC genes are the most polymorphic genes diversity in marine mammals makes it difficult to draw con- in vertebrates, and they encode cell-surface glycoproteins clusions, especially since many studies are based on relatively that bind and present antigens to T cells, triggering an few individuals per species (Hayashi et al. 2003; Xu et al. appropriate immune response. Class II molecules are pri- 2009). Limited number of studies has been performed on bot- marily expressed on antigen-presenting cells, where they tlenose dolphin MHC genes. Yang et al. (2007) detected one bind peptides derived from the processing of extracellular DQB and two DRB loci in Tursiops, while subsequent study pathogens such as bacteria or parasites. of 42 T. truncatus individuals from Taiwanese waters showed The extreme variability at MHC loci is thought to deter- moderate variation at the DQB locus (Yang et al. 2008). We mine the ability of individuals to respond to pathogens and are unaware of studies examining DRA and DQA polymor- parasites and thus to influence individual fitness and long- phism in bottlenose dolphins on a population level. term population survival (Hughes 1991; Hughes and Nei To help clarify and deepen our understanding of MHC 1992). Most of this polymorphism occurs in exon 2, which genetic diversity in bottlenose dolphins, we investigated the encodes the peptide-binding region (PBR) that recognises diversity of MHC class II DRA, DQA and DQB loci in a and binds antigens. MHC polymorphism is believed to be bottlenose dolphin population from the Adriatic Sea. We maintained by balancing selection, which has been pro- determined MHC class II haplotypes and compared them posed to occur in several forms: heterozygote advantage with haplotypes found in other Mediterranean locations. or overdominance, which predicts that heterozygous indi- We used our results to discuss and contribute to a better viduals can respond to a broader range of antigens than can understanding of molecular signatures of natural selection homozygous individuals (Doherty and Zinkernagel 1975); in dolphin MHC evolution. negative frequency-dependent selection, also referred to as rare-allele advantage selection, which favours rare alleles presumably because they confer greater resistance to new Materials and methods pathogens (Takahata and Nei 1990), and diversifying selec- tion, according to which heterogeneous selective pres- Laboratory procedures sures promote local adaptation and maintain MHC allele diversity on a local scale (Hedrick 2002). These forms of Tissue samples from 62 bottlenose dolphin carcasses were balancing selection are not mutually exclusive: several collected from 1997 until 2011 along the eastern (Croatian) 1 3 Mar Biol (2014) 161:2407–2422 2409 Fig. 1 The location
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