@misc{oai:ir.soken.ac.jp:00000951,
 author = {野田, 令子 and ノダ, レイコ and NODA, Reiko},
 month = {2016-02-17},
 note = {There are three common alleles (A, B, and O) at the human ABO blood group locus.　The A and B alleles code for glycosyltransferases which transfer GalNAc and galactose, respectively, while O is a null allele incapable of coding for a functional glycosyltransferase. This difference of the glycosyltransferase activity between A and B is determined by the two amino acid substitutions in the downstream region of exon 7, and the same differences were observed for A and B alleles in non-human primates. Some kind of natural selection may be operating on this locus to maintain the polymorphism of A and B in primates. Therefore, it is interesting to determine the gene geneology of this ABO gene, so as to see whether the parallel changes or ancestral polymorphism is responsible for the persistence of the ABO polymorphism in primates.<br />     First I determined the nucleotide sequence of about 450bp region in exon 7 of 50 alleles for the following species; orangutan, agile gibbon, white-handed gibbon siamang, Japanese macaque, moor macaque, Celebes crested macaque, barbary macaque, bonobo, gorilla, olive baboon, yellow baboon, and mantled baboon. Then I compared these results with the 64 published nucleotide sequence data of human,  chimpanzee, gorilla, orangutan rhesus macaque, crab-eating macaque, and yellow baboon. The phylogenetic network of this region was very complex, but in the macaques network, B type alleles of moor macaque was closely related to A type alleles of Celebes crested macaque rather than B type of Japanese, crab-eating, and rhesus macaque. In this case, B type allele was supposed to evolve in the moor macaque lineage independently from the lineage of Japanese, crab-eating, and rhesus macaque.<br />     I then determined genomic nucleotide sequences of about 2kb region between ABO exon 5 to exon 7 of three species of gibbon (white-handed gibbon, agile gibbon, and siamang), bonobo, and gorilla, and also determined those of about 1.5kb region between exon 6 and exon 7 of orangutan, four species of macaque (Celebes crested macaque, moor macaque, barbary macaque, and Japanese macaque), and three species of baboon (yellow, olive, and mantled). I analyzed those newly determined sequences with other primate ABO blood group gene sequences.<br />     The patterns of the variant sites in gibbon suggested that A and B alleles were already polymorphic in the ancestral species of white-handed and agile gibbons soon after speciation of siamang, and a recombination between these two alleles occurred before speciation of white-handed and agile gibbons. In the orangutan lineage, it is suggested that the gene introgression occurred from the ancestral species of agile and white-handed gibbon, and the intragenic recombination or gene conversion event followed. I also found that in macaques, type B allele appeared both in the Japanese, crab-eating, and rhesus macaque lineages and in the Sulawesi macaque lineage independently. In the case of baboon, the relationship of A type and B type alleles was intermingled, suggesting the existence of ancestral polymorphism.<br />     I also determined the sequence of the ABO intron 2 of the same genomic DNA samples of human, orangutan, agile gibbon, white-handed gibbon, siamang, Japanese macaque, Celebes crested macaque, barbary macaque, bonobo, gorilla, and olive baboon. The phylogenetic tree of this region was consistent with the species tree. This region is 5kb upstream of the ABO intron 5 region. So I can determine that the affected region of the gene introgression event between gibbon and orangutan may start between exon 3 and exon 6. The survival of a short fragment that introgressed from gibbon might have been influenced from the selection effect of the critical sites of A and B, because the region that survived in the orangutan lineage is tightly linked to critical sites.<br />     The inconsistency between gene tree and species tree can occur as extensively studied for the human-chimpanzee-gorilla lineage. In this case the time between two speciation times was short, so ancestral polymorphism may cause this inconsistency. To resolve this for phylogenetic estimation, one must use multiple independent loci. In the case of gibbons and orangutan, I found the same problem as in the human-chimpanzee-gorilla relationship. There are 20 data sets that contain the orangutan and gibbon sequences and the orthologous ones for sequences in human and African apes in the DDBJ/EMBL/Gen Bank International Nucleotide Sequence Database, and 6 phylogenetic trees out of these 20 showed the trees inconsistent to the species tree. These inconsistent relationships may be caused by the ancestral polymorphism, the misplacement of the root, or the stochastic error based on short length. In some cases of these data sets, the length of sequence was too short to discuss the phylogenetic relationship between gibbon and orangutan to compare the ABO gene, and the amount of DNA data was not enough.<br />     I therefore determined nucleotide sequences, those length are from 430bp to 1800bp, of mitochondrial DNA (16SrRNA) and five nuclear DNA genes (amelogenin X, amelogenin Y, N-formyl peptide receptor, FPR-like gene, and alpha-1, 3-galactosyltransferase) using the genomic DNA samples of the same primate species used for the study of the ABO blood group gene. Mitochondrial DNA data suggested the separation of two orangutan subspecies (Bornean orangutan; P. pygmaeus pygmaeus and Sumatran orangutan; P. p. abelii). But three species of baboon were very similar to each other not only for the ABO data but also for mitochondria and FPR1. In the case of baboon, the ancestral polymorphism was supported not only for the ABO blood group gene but also for the other regions of nuclear and mtDNA, so the effect of natural selection of ABO region is not clear from the result of baboon. In contrast,  it is suggested by this study that the type changes between A and B occurred in the macaque lineage at least two times. In the case of human, chimpanzee and gorilla, the type change occurred more than once. Furthermore, in the gibbon lineage, the polymorphism of A and B was maintained more than 5 million years in ancestral species between agile and white-handed gibbons. These results suggest that the some kind of selection might act on the ABO locus.<br />     The sequences newly determined and sequences retrieved from the DNA database are compatible with the species tree except for the region between exons 6 and 7 of the ABO blood group gene. Therefore, the region where the putative gene introgression event from ancestral gibbon to ancestral orangutan occurred can be narrowed to that DNA region of the orangutan genome. This result also suggests that some kind of selection might have acted in the ABO gene, especially in the critical sites. In conclusion, the existence of a Darwinian selection may be the reason why the evolutionary patterns of the ABO blood group gene is inconsistent with the species tree in various primate species., 総研大甲第466号},
 title = {Evolutionary study of primate mitochondrial andnuclear genes with special reference to the ABOblood group genes},
 year = {}
}