| In humans, malaria is caused by parasites of the genus Plasmodium . Humans are not the only primate species that harbor Plasmodium parasites; orangutans also harbor two species. In this study, the α globin region of orangutans is forwarded as a candidate locus involved in resistance. The molecular population genetics of the orangutan's α-2 globin (HBA2) locus are investigated, in order to test for the action of natural selection. Two selective hypotheses, balancing selection and a selective sweep, are tested against the null model of neutral evolution. To test these hypotheses, 33 orangutan haplotypes from both Bornean and Sumatran subspecies were collected from 1.46 kilobases of the α-2 globin region. Two aspects of the data are inconsistent with the expectations of neutral evolution: a heterogeneous distribution of the polymorphisms and an excess of linkage disequilibrium. The patterns of linkage and recombination are also suggestive of natural selection: a single amino acid site replacement site is linked to different alternative states within each subspecies. These two distinct haplotypes are segregated within subspecies, and the genetic variation is differentiated between haplotype classes. This strongly suggests that the replacement allele has spread through two populations after two distinct origination events. These observations are consistent with a model of relatively recent balancing selection operating on the locus.; Triplicated α globin genes have been described in a number of tropical primates [Boyer et al. 1971a, 1971b, 1973; Zimmer et al. 1980; Takenaka et al. 1991, 1993], though these loci are not all homologous. The polymorphic triplicated α-globin locus of orangutans is also investigated herein from a phylogenetic perspective. Phylogenetic analysis shows that the event leading to triplication occurred in the common ancestor of Sumatran and Bornean orangutans. Based on likelihood ratio tests and pairwise Ka/KS analyses, the triplicated α-trip globin gene is evolving in a neutral or positively selected environment. This contrasts with purifying selection which has operated on the α-2 globin locus. Structural and phylogenetic analyses of the triplicated α-globin's predicted amino acid chain show evidence of correlated changes among sites in the α-trip gene, which point towards a history of positive evolutionary change. A hypothesis for the evolution of the triplicated α globin gene is offered, along with a potential role for this novel gene as a thalassemic adaptation to malaria. The triplicated α globin gene will also be examined in light of the recent debate on the molecular evolutionary fate of duplicated genes. |
