Major Histocompatibility Complex (MHC) Evolution in Platyrrhine Monkeys: Duplications and Hybridization as Sources of Adaptive Genetic Variation

Abstract

Genetic variation is the foundation for a population to adapt to an environment that is constantly changing. Investigating the mechanisms through which genetic variation is acquired and maintained can inform how populations evolve in response to environmental pressures. One of the most variable genomic regions is the Major Histocompatibility Complex (MHC), the hallmark of adaptive immunity. In my dissertation, I explore mechanisms affecting MHC genetic variation with a focus on hybridization as a source of adaptive genetic variation. In Chapter 1, I characterized three MHC Class II loci (DQA1 exon 2, DQB1 exon 2 and DQB2 exon 2) in four species of howler monkeys (genus Alouatta): A. palliata, A. pigra, A. caraya and A. guariba. These species had not been characterized for any of these MHC loci. Overall, platyrrhines, monkeys of the Americas, are an understudied primate group for MHC genes. The genotypes derived from this study of these four Alouatta species suggested duplications at the MHC-DQA1 and MHC-DQB1 genes. Different lines of evidence (genotypes, genome search, gene prediction and phylogenetic analysis) supported at least one duplication event for DQA1 and two duplication events for DQB1. Additionally, sequences from individuals of two more divergent platyrrhine lineages (Aotus and Callithrix) indicate these duplications may be present across platyrrhines and constitute trans-specific polymorphisms, in which polymorphic gene lineages persist through speciation events. These analyses support positive and balancing selection maintaining the diversity of MHC-DQ in platyrrhines. In Chapter 2, I evaluated MHC genetic diversity across the distribution of A. palliata. I analyzed populations from Mexico, Costa Rica and Peru at seven MHC loci. I found that populations in Mexico were monomorphic at all seven loci while the other populations exhibited greater genetic diversity. These three populations also had signatures of population structure. My results suggested positive selection acting on DRB and DQB1-L3. The remaining loci appear to be evolving neutrally, mirroring patterns of genetic diversity at neutral markers. The Mexican population showed extremely low levels of genetic diversity at each MHC locus. This reduced functional diversity may have serious implications for the conservation of the Mexican population. In Chapter 3, I assessed introgression of MHC alleles in the Alouatta hybrid zone (A. palliata x A. pigra). The level of genomic admixture (based on a hybrid index) for each individual analyzed in the hybrid zone has been previously estimated. I used these values to evaluate the level and direction of introgression at each locus. I found asymmetric introgression from A. palliata into A. pigra at all loci. Moreover, five out of six MHC loci analyzed showed increased introgression compared to neutral expectations, suggesting alleles at MHC loci from one species can confer advantages in a second species following hybridization. This is the first study to provide empirical evidence, in a primate hybrid zone, that supports previous claims of adaptive introgression of MHC genes in humans. This dissertation investigated MHC genetic variation in platyrrhines and the mechanisms and sources responsible for this variation. I provided evidence for gene duplication and hybridization as important sources of adaptive variation maintained through selection. Also, I implemented MHC loci as markers for evaluating genetic diversity, which are more informative of adaptive genetic variation than traditionally used neutral markers. This work provides new insight into the evolutionary history of MHC in platyrrhines and primates more generally.