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Human presence in Southeast Asia dates back to at least 40,000 years ago, when the current islands formed a continental shelf called Sundaland. In the Philippine Islands, Peninsular Malaysia, and Andaman Islands, there exist indigenous groups collectively called Negritos whose ancestry can be traced to the “First Sundaland People.” To understand the relationship between these Negrito groups and their demographic histories, we generated genome-wide single nucleotide polymorphism data in the Philippine Negritos and compared them with existing data from other populations. Phylogenetic tree analyses show that Negritos are basal to other East and Southeast Asians, and that they diverged from West Eurasians at least 38,000 years ago. We also found relatively high traces of Denisovan admixture in the Philippine Negritos, but not in the Malaysian and Andamanese groups, suggesting independent introgression and/or parallel losses involving Denisovan introgressed regions. Shared genetic loci between all three Negrito groups could be related to skin pigmentation, height, facial morphology and malarial resistance. These results show the unique status of Negrito groups as descended from the First Sundaland People.

Various genetic data (classic markers, mitochondrial DNAs, Y chromosomes and genome-wide single-nucleotide polymorphisms (SNPs)) have confirmed the coexistence of three major human populations on the Japanese Archipelago: Ainu in Hokkaido, Ryukyuans in the Southern Islands and Mainland Japanese. We compared genome-wide SNP data of the Ainu, Ryukyuans and Mainland Japanese, and found the following results: (1) the Ainu are genetically different from Mainland Japanese living in Tohoku, the northern part of Honshu Island; (2) using Ainu as descendants of the Jomon people and continental Asians (Han Chinese, Koreans) as descendants of Yayoi people, the proportion of Jomon genetic component in Mainland Japanese was ~18% and ~28% in Ryukyuans; (3) the time since admixture for Mainland Japanese ranged from 55 to 58 generations ago, and 43 to 44 generations ago for the Ryukyuans, depending on the number of Ainu individuals with varying rates of recent admixture with Mainland Japanese; (4) estimated haplotypes of some Ainu individuals suggested relatively long-term admixture with Mainland Japanese; and (5) highly differentiated genomic regions between Ainu and Mainland Japanese included EDAR and COL7A1 gene regions, which were shown to influence macroscopic phenotypes. These results clearly demonstrate the unique status of the Ainu and Ryukyuan people within East Asia.

The Japanese Archipelago stretches over 4000 km from north to south, and is the homeland of the three human populations; the Ainu, the Mainland Japanese and the Ryukyuan. The archeological evidence of human residence on this Archipelago goes back to >30 000 years, and various migration routes and root populations have been proposed. Here, we determined close to one million single-nucleotide polymorphisms (SNPs) for the Ainu and the Ryukyuan, and compared these with existing data sets. This is the first report of these genome-wide SNP data. Major findings are: (1) Recent admixture with the Mainland Japanese was observed for more than one third of the Ainu individuals from principal component analysis and frappe analyses; (2) The Ainu population seems to have experienced admixture with another population, and a combination of two types of admixtures is the unique characteristics of this population; (3) The Ainu and the Ryukyuan are tightly clustered with 100% bootstrap probability followed by the Mainland Japanese in the phylogenetic trees of East Eurasian populations. These results clearly support the dual structure model on the Japanese Archipelago populations, though the origins of the Jomon and the Yayoi people still remain to be solved.

Haplotype frequencies of the beta-globin gene cluster of Han Chinese at Beijing, Xi'an, and Kunming were estimated, and their mutual genetic relationships were examined and compared to those of Buryats, Khalkhs, Evenkis, Oroqens, Koreans, and Colombian Amerindians. A major 5' subhaplotype (5' to the delta-globin gene), a major 3' subhaplotype (in and 3' to the beta-globin gene), and a major haplotype (combination of 5' and 3' subhaplotypes) are represented as + - - - -, - +, and + - - - - - +, respectively, and found in all three Han Chinese. A rare 5' subhaplotype, - - - - -, which is one of the possible ancestral types, was found only in Han Chinese at Kunming at low frequency (0.013), and a rare 3' subhaplotype, - -, was also observed in all three Han Chinese at low frequencies (0.009-0.014). The present haplotype frequency study suggested that the highest genetic affinity was found between Han Chinese at Beijing and those at Xi'an; the next highest was between Han Chinese at Beijing and Koreans, followed by that between Han Chinese at Beijing and Khalkhs, then that between Han Chinese at Xi'an and those at Kunming or Khalkhs, and finally that between Han Chinese at Beijing and those at Kunming. A genetic boundary between northern and southern Han Chinese was not evident in the present study.

Beta-globin gene cluster haplotype frequencies of 169 Khalkhs and 145 Buryats were estimated, and their characteristics were compared with those of Evenkis, Oroqens, Koreans, Japanese, and three Colombian Amerindian groups. The present study suggests that Colombian Amerindians diverged first from Asian populations and then Buryats diverged from other Asian populations.

Historic Japanese culture evolved from at least two distinct migrations that originated on the Asian continent. Hunter-gatherers arrived before land bridges were submerged after the last glacial maximum (12,000 years ago) and gave rise to the Jomon culture, and the Yayoi migration brought wet rice agriculture from Korea beginning approximately 2,300 years ago. A set of 81 Y chromosome single nucleotide polymorphisms (SNPs) was used to trace the origins of Paleolithic and Neolithic components of the Japanese paternal gene pool, and to determine the relative contribution of Jomon and Yayoi Y chromosome lineages to modern Japanese. Our global sample consisted of2,500 males from 39 Asian populations, including six populations sampled from across the Japanese archipelago. Japanese populations were characterized by the presence of two major (D and O) and two minor (C and N) clades of Y chromosomes, each with several sub-lineages. Haplogroup D chromosomes were present at 34.7% and were distributed in a U-shaped pattern with the highest frequency in the northern Ainu and southern Ryukyuans. In contrast, haplogroup O lineages (51.8%) were distributed in an inverted U-shaped pattern with a maximum frequency on Kyushu. Coalescent analyses of Y chromosome short tandem repeat diversity indicated that haplogroups D and C began their expansions in Japan approximately 20,000 and approximately 12,000 years ago, respectively, while haplogroup O-47z began its expansion only approximately 4,000 years ago. We infer that these patterns result from separate and distinct genetic contributions from both the Jomon and the Yayoi cultures to modern Japanese, with varying levels of admixture between these two populations across the archipelago. The results also support the hypothesis of a Central Asian origin of Jomonese ancestors, and a Southeast Asian origin of the ancestors of the Yayoi, contra previous models based on morphological and genetic evidence.

The Ainu, a minority ethnic group from the northernmost island of Japan, was investigated for DNA polymorphisms both from maternal (mitochondrial DNA) and paternal (Y chromosome) lineages extensively. Other Asian populations inhabiting North, East, and Southeast Asia were also examined for detailed phylogeographic analyses at the mtDNA sequence type as well as Y-haplogroup levels. The maternal and paternal gene pools of the Ainu contained 25 mtDNA sequence types and three Y-haplogroups, respectively. Eleven of the 25 mtDNA sequence types were unique to the Ainu and accounted for over 50% of the population, whereas 14 were widely distributed among other Asian populations. Of the 14 shared types, the most frequently shared type was found in common among the Ainu, Nivkhi in northern Sakhalin, and Koryaks in the Kamchatka Peninsula. Moreover, analysis of genetic distances calculated from the mtDNA data revealed that the Ainu seemed to be related to both the Nivkhi and other Japanese populations (such as mainland Japanese and Okinawans) at the population level. On the paternal side, the vast majority (87.5%) of the Ainu exhibited the Asian-specific YAP+ lineages (Y-haplogroups D-M55* and D-M125), which were distributed only in the Japanese Archipelago in this analysis. On the other hand, the Ainu exhibited no other Y-haplogroups (C-M8, O-M175*, and O-M122*) common in mainland Japanese and Okinawans. It is noteworthy that the rest of the Ainu gene pool was occupied by the paternal lineage (Y-haplogroup C-M217*) from North Asia including Sakhalin. Thus, the present findings suggest that the Ainu retain a certain degree of their own genetic uniqueness, while having higher genetic affinities with other regional populations in Japan and the Nivkhi among Asian populations.

Haplotype frequencies of the beta-globin gene cluster were estimated for 114 Evenkis and 81 Oroqens from northeast China, and their characteristics were compared with those in Japanese, Koreans, and three Colombian Amerindian groups of South America (Wayuu, Kamsa, and Inga tribes). A major 5' subhaplotype (5' to the delta-globin gene) was + - - - - in Evenkis, whereas + - - - -, - + + - +, and - + - + + were the major subhaplotypes in Oroqens. One possible candidate for an ancestral 5' subhaplotype, - - - - -, was found in one Evenki (0.5%) and three Oroqen chromosomes (2.0%). They were observed as heterozygous forms for + ---- and -----. Major haplotypes were +-----+, + -----+-, and + - - - - + + in Evenkis, whereas they were +-----+,-++-+-+, +----+-, and -+-++-+ in Oroqens. The lowest Nei's genetic distance values of Evenkis or Oroqens based on the 5' subhaplotype frequency distributions were observed in relation to the Wayuu or Koreans, respectively, but those of Evenkis and Oroqens based on the haplotype frequency distributions were found in relation to Koreans.

The phylogeny of butterflies, Parnassius stubbendorfii and P. glacialis, collected at various localities in the Japan archipelago and the eastern part of the Asian continent was analyzed using mitochondrial DNA sequences coding for NADH dehydrogenase subunit 5 (805 bp). The molecular phylogenetic trees revealed that P. glacialis and P. stubbendorfii diverged from a common ancestor, and then the populations inhabiting the Japan archipelago and the Asian continent diverged in each species. The reliability of these divergences was supported by high bootstrap values. The divergences within the Japan archipelago and within the Asian continent in each species were unclear because of low bootstrap values. The genetic distance and a rough time-estimation in the UPGMA tree suggest that the both populations of P. glacialis and P. stubbendorfii may have been isolated in the Japan archipelago at the early time (about 1.7-2.0 Mya) of the glacial period in the Pleistocene. The genetic distance between the Japanese and the continental subspecies may be large enough that they can be classified as different species, in comparison with the genetic distances among some other parnassian species.

Population genetic study of nine aboriginal ethnic groups of Taiwan(Ami, Atayal, Bunun, Paiwan, Puyuma, Rukai, Saisiat, Tsou, and Yami) wascarried out. Twelve red cell enzymes (AcP, AK, CA1, CA2, EsD, GLO, GPT, GOT, LDH, MDH, PGD, and PGM1) were analyzed by isoelectric focusingmethod and starch gel electrophoretic method. Six loci (AcP, EsD, GLO, GPT, PGD, and PGM1) were polymorphic. Three alleles (PGM1*6, GPT*6, andEsD*7) were in relatively higher allele frequencies in Taiwan aboriginalpopulations, and we found homozygotes for those alleles. Phylogenetic relationshipbased on genetic distances among those ethnic groups more or less fit to theirgeographical distribution, but not to linguistic classification.

Based on the morphological characteristics of the skull and teeth, Hanihara ([1991] Japan Review 2:1-33) proposed the "dual structure model" for the formation of modern Japanese populations. We examine this model by dividing it into two independent hypotheses: 1) the Upper Paleolithic population of Japan that gave rise to the Neolithic Jomon people was of southeast Asian origin, and 2) modern Ainu and Ryukyuan (Okinawa) populations are direct descendants of the Jomon people, while Hondo (Main Island)-Japanese are mainly derived from the migrants from the northeast Asian continent after the Aeneolithic Yayoi period. Our aim is to examine the extent to which the model is supported by genetic evidence from modern populations, particularly from Japan and other Asian areas. Based on genetic distance analyses using data from up to 25 "classic" genetic markers, we find first that the three Japanese populations including Ainu and Ryukyuan clearly belong to a northeast Asian cluster group. This negates the first hypothesis of the model. Then, we find that Ainu and Ryukyuans share a group contrasting with Hondo-Japanese and Korean, supporting the second hypothesis of the model. Based on these results, we propose a modified version of the dual structure model which may explain the genetic, morphological, and archaeological evidence concerning the formation of modern Japanese populations.

Five polymorphisms involving two paternally inherited loci were surveyed in 38 world populations (n = 1,631) to investigate the origins of Native Americans. One of the six Y chromosome combination haplotypes (1T) was found at relatively high frequencies (17.8-75.0%) in nine Native American populations (n = 206) representing the three major linguistic divisions in the New World. Overall, these data do not support the Greenberg et al. (1986) tripartite model for the early peopling of the Americas. The 1T haplotype was also discovered at a low frequency in Siberian Eskimos (3/22), Chukchi (1/6), and Evens (1/65) but was absent from 17 other Asian populations (n = 987). The perplexing presence of the 1T haplotype in northeastern Siberia may be due to back-migration from the New World to Asia.

The Ainu people are considered to be the descendants of preagricultural native populations of northern Japan, while the majority of the population of contemporary Japan (Wajin) is descended mainly from postneolithic migrants. Polymorphisms of the HLA-DRB1, DRB3, and DQB1 alleles were investigated in DNA samples of 50 Ainu living in Hidaka district, Hokkaido. Unique features of the Ainu in this study were high incidences of DRB1*1401, DRB1*1406, and a newly described allele, DRB1*1106 (20%, 17%, and 5%, respectively). On the other hand, several common alleles in Wajin (DRB1*1502, 1302, 0803, and 1501) were found at relatively low frequencies (1–2%) in Ainu. Previously DRB1*1406 was described as a characteristic allele of some Native American or northeast Asian ethnic groups, and DRB1*1106 had been found in only two Singapore Chinese and one Korean. Principal component analysis of various populations based on HLA class II allele frequencies places the Ainu population midway between other east Asian populations, including Wajin, and Native Americans. These observations may support the hypothesis that the Ainu people are the descendants of some Upper Paleolithic populations of northeast Asia from which Native Americans are also descended. © 1996 Wiley-Liss, Inc.

ADA subtype polymorphism in nine aboriginal populations (Gaoshan) of Taiwan was studied by means of the IEF method. A new ADA variant allele, ADA*Taiwan1, was in a high allele frequency in two Gaoshan populations, the Amis and the Paiwans. Another new variant, ADA*Taiwan2, was found in only one case of heterozygote in the Saisiats. Allele frequencies of a common allele, ADA*2, in the Paiwans and the Amis were the highest among the Asian populations so far studied.

この総説は, 日本人の起源の問題について, 分子人類学の立場から, 何が, どこまでいえるのかを紹介し, 今後の総合的な日本人研究への一助とする目的で書かれた。検討のための土台として, 埴原の「二重構造モデル」が用いられた。このモデルを, (1)「原日本人」は東南アジア起源である, (2) 現代日本人の諸集団の形成には、「原日本人」と北東アジア系の渡来人という主として2つの系統を異にする集団が関わっている, との2つの部分仮説にわけ, それぞれを個別に検討した。分子人類学的に重要な資料としては, 古人骨のミトコンドリアDNAの塩基配列 (宝来ら) と古典的遺伝標識の遺伝子頻度を用いた多変量解析 (根井, および筆者ら) などがある。前者は, 原日本人の南方起源説にとり有利な資料を, また, 後者は, 反対に, 原日本人の北方起源説を支持する資料を提供している。また, 埴原のいう「二重構造」の存在についても, 意見がわかれている。このような不一致点をどのように説明するかが, 大きな問題である。本論文で筆者は, 問題点の所在を明らかにすると共に, 将来の検討に対する資料として, いくつかの提案をした。

In our previous study, both of Y-associated alleles, Y1 and Y2, were detected in Japanese and Koreans, but only the Y1 allele was detected in each of other populations including Chinese in both Beijin and Guangzhou areas, Caucasians, Africans, and Jewish. In the present study, these observations were extended to other ethnic groups in East Asia. Evenks in central Siberia and Khalkhs in Mongolia had only the Y1 allele. On the other hand, two ethnic groups, Fo-lo and Hakka, in Taiwan had both of the Y1 and the Y2 alleles. Three of the eight Y2-positive men, 2 Fo-lo and a Hakka, shared family name Chen. Both Hakka people and ancestors of Chen families could be traced to the Province of Henan in northern China in early 4th century. They arrived in Fujian/Guangdong area in the south-east China via various routes and then some of them migrated to Taiwan in the 18th century. It is tempting to speculate that the Y2 allele may be originated from an ancestral population in Henan from which, Japanese, Koreans, and some of the Taiwanese diverged.

A population genetic study was carried out on six populations (two Li populations, two Miao populations, one Hui population, and one Han population) in Hainan Island, Southern China. Allele frequency data for these six populations and those for some other Asian populations were used to estimate genetic distances between populations, and genetic affinity dendrograms and networks were constructed by using UPGMA and the neighbor-joining method, respectively The two Li populations showed a close relationship, while the two Miao populations were relatively distant from each other. These six populations of Hainan Island showed a close affinity with Zhuang of Southern China, Thailanders, and Javanese, but they are distant from populations around northern China (Japanese, Mongolian, and Korean). Divergence time between the Li-Miao group and Japanese was estimated to be roughly 19, 000-26, 000 years.

Results obtained in a joint Japanese-Chinese field study in Hainan Island are presented. Three national minority groups, Li, Miao and Hui, together with Han as control were studied. A total of 23 blood genetic markers comprising 9 blood groups, 7 red cell enzymes and 7 serum proteins, and also alpha and beta thalassemias were examined, and phenotype and allele frequencies are tabulated. The distributions of allele frequencies differ markedly among the four groups, although falling in general within that of southern Chinese. Two sample groups of Li, i.e., Qi-Li and Benti-Li, are more similar to each other than the two sample groups of Miao, probably reflecting different backgrounds in migratory history of Li and Miao. Judging from high frequencies of both alpha and beta thalassemias and G-6PD deficiency in Li and Miao, it was considered that malaria played a major role in determining these characteristics.

The nucleotide sequence of 807 bp of the mtDNA- ND5 locus of Parnassius davydovi (Churkin, S. 2006. A new species of Parnassius Latreille, 1804, from Kyrgyzstan (Lepidoptera, Papilionidae). Helios (Moskow) 7,142-158), was determined. This butterfly was unexpectedly discovered recently in Kyrgyzstan, and we wished to shed light on its molecular phylogenetic relationship to other Parnassian butterflies, as well as to the related taxa in the subfamily Parnassiinae of the family Papilionidae. Using the ML method with the GTR+I+Γ model, we inferred the phylogenetic tree for 60 Parnassius individuals together with materials of the related genera in the subfamily Parnassiinae ( Hypermnestra , Archon , Luehdorfia , Bhutanitis , Allancastria , Zerynthia and Sericinus ) with Papilio machaon as an out-group. It was found that P. davydovi is a distinct species most closely related to P. loxias in clade VI among the eight clades, or species groups of Parnassius . The morphological diversity in the form of sphragis, the attachment to the female abdomen formed by the male during copulation, is characteristic to this clade, and we inferred the order of emergence of the different sphragis forms during evolution. Attempts to estimate the divergence times between related taxa were also made. It was inferred that the relatively rapid radiation of Parnassian butterflies started at about 24 MYA BP, while P. davydovi diverged from P. loxias at about 10 MYA BP.

The hinge region of the immunoglobulin molecule is responsible for antigen-binding and cross-linking reactions, varying the distance between the two antigen-binding sites. As the amino acid sequence of the hinge region is identical among immunoglobulin molecules of the same (sub)class, it has been regarded as a constant region. By comparison of the nucleotide sequences among primate C alpha genes, it is clear that there is a wide variety of length among the hinge regions of hominoid C alpha genes, which basically consist of tandem repeats of a 15 base-pair sequence. This reiterated structure probably facilitates rapid evolutionary changes in the length of the hinge region. The hinge region of the Old World monkey C alpha gene has a non-reiterated structure whose nucleotide sequence is quite different from those of the hominoid C alpha genes, although its surrounding region is conserved during evolution. This unusual hypervariability reveals that the hinge region has evolved as a semi-variable region in contrast to its constant character from an ontogenic viewpoint.

Restriction fragment length polymorphism (RFLP) of the two genes for complement C4A and C4B was studied in 56 Japanese patients with rheumatoid arthritis (RA) and 161 normal individuals. Hindlll digestion revealed six common patterns, from which the segregation of three common RFLP-types were deduced; 32-15 kb, 32-25-15 kb, and 32-20-13-6.5 kb. The last type showed positive associations with C4B5 and HLA-DR4. In the RA patients, an increase of this type was found as well as a decrease of the 32-15 kb/32-25-15 kb heterozygotes.

Phylogenetic relationships among species of the genus Parnassius and its related taxa were analyzed by comparing nucleotide sequences of mitochondrial 16S ribosomal RNA (504 sites) and NADH-dehydrogenase subunit 1 (469 sites). In the phylogenetic trees, Parnassius was found to be most closely related to Hypermnestra helios, whereas Archon apollinus, which has been classified in the tribe Parnassiini together with Parnassius and Hypermnestra, was more closely related to members of the tribe Zerynthiini. Within the Parnassius clade, six major clades corresponding to species groups were well supported, although the phylogenetic relationships among them were not clear. Although the results of the present study were in agreement with those of a previous phylogenetic study based on mitochondrial NADH-dehydrogenase subunit 5 sequences, our study strongly supported a close relationship between Parnassius and Hypermnestra, which was not well supported in the previous study.

Sequences of 777 bp of mtDNA-ND5 locus were determined in order to shed light on the molecular systematics and evolution of the "Apollo" butterflies. Examined were nearly all of about 50 species of the genus Parnassius, together with seven species of the allied genera in the subfamily Parnassiinae (Papilionidae). The NJ and the MP phylogenetic trees show that the "Apollos" constitute a monophyletic group, comprising a number of cluster groups probably reflecting a relatively rapid radiation in evolution. The clusters of species-groups denoted I-VIII correspond to those species-groups recognized on the basis of morphological characters. Our findings will also help understand the biological relationships among several species or subspecies on which the classical taxonomy is in dispute. The unexpected finding is that among the samples of allied genera compared, Hypermnestra helios appears to be the most closely related to the "Apollos", despite morphological and behavioral dissimilarity. Furthermore, in contrast to the previous higher taxonomy, Archon apollinus which is classified in the tribe Parnassiini was found genetically closer to the tribe Zerynthiini, raising a taxonomic controversy.

The molecular basis and biochemical mediators of genetic growth propensity and adult height achievement in the general population are largely unknown. Pygmies represent one extreme of the height spectrum that may provide important clues regarding this issue. Previous studies in pygmies from Africa and Papua-New Guinea have shown decreased serum levels of growth hormone binding protein (GHBP), the circulating ectodomain of the growth hormone receptor (GHR). By inference, a similar limitation in tissue GHR expression has been assumed to be responsible for the partial growth hormone (GH) resistance observed in African pygmies. It is not clear how generalizable this concept is to other populations. To address this question, we studied two pygmy populations from the Philippines (Aeta and Mamanwa people) that are unrelated to the African pygmies. Serum GHBP and IGF-I levels were significantly decreased in both pygmy populations, compared to normal-statured Philippino controls. The results, together with previous observations in African and New Guinean pygmies, indicate that short stature is associated with low serum GHBP levels in pygmy populations of diverse origins and in different parts of the world. This strengthens the tentative postulate that the GHBP/GHR system plays an important role in the genetic and perhaps nutritional determination of adult stature in humans. Molecular genetic studies of the GHR gene in various pygmy populations may shed further light on the mystery of pygmy short stature.

DNA variation on the non-recombining portion of the Y chromosome was examined in 610 male samples from 14 global populations in north, east, and southeast Asia, and other regions of the world. Eight haplotypes were observed by analyses of seven biallelic polymorphic markers ( DYS257(108), DYS287, SRY(4064), SRY(10831), RPS4Y(711), M9, and M15) and were unevenly distributed among the populations. Maximum parsimony tree for the eight haplotypes showed that these haplotypes could be classified into four distinct lineages characterized by three key mutations: an insertion of the Y Alu polymorphic (YAP) element at DYS287, a C-to-G transversion at M9, and a C-to-T transition at RPS4Y(711). Of the four lineages, three major lineages (defined by the allele of YAP(+), M9-G, and RPS4Y-T, respectively) accounted for 98.6% of the Asian populations studied, indicating that these three paternal lineages have contributed to the formation of modern Asian populations. Moreover, phylogenetic analysis revealed three monophyletic Asian clusters, which consisted of north Asian, Japanese, and Han Chinese/southeast Asian populations, respectively. Coalescence analysis in the haplotype tree showed that the estimated ages for three key mutations ranged from 53,000 to 95,000 years, suggesting that the three lineages were separated from one another during early stages of human evolutionary history. The distribution patterns of the Y-haplotypes and mutational ages for the key markers suggest that three major groups with different paternal ancestries separately migrated to prehistoric east and southeast Asia.

This chapter summarizes the results of my population genetic studies concerning various ethnic groups in eastern Asia and western Pacific with special reference to the origins of (1) the Japanese peoples, and (2) the so-called Mongoloid groups. On the first topic, I will show that Kazuro Hanihara’s “dual structure model” is only partly supported by genetic evidence. As for the second, I will argue that the genetic diversity among eastern Asian, Pacific and American populations is so extensive that the classic racial concept of “Mongoloid” is no longer tenable. It is also indicated that contrary to the classic view of a single south-east Asian origin of these populations, there were at least two independent sources for human migrations in eastern Asia during the Upper Paleolithic Times from about 50 000 to 20 000 years BP.

Human Zn-alpha 2-glycoprotein (ZAG) in plasma samples from twelve populations was tested by immunoblotting after polyacrylamide gel isoelectric focusing. Eleven ZAG phenotypes produced by one common and nine rare alleles, including five new ones (ZAG*6–ZAG*10), were detected. Additionally, an application of separator IEF with N′-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (HEPES) was found to be useful for discriminating the rare ZAG 7 band.

The nucleotide sequence of a HLA-DRB gene with a predominant subtype of DRw8 specificity in Japanese (DR8.1) was determined with single-stranded DNA enzymatically amplified by polymerase chain reaction (PCR). The sequence differs at a single amino acid from both of the published DRw8/Dw8.1 and DRw8/Dw8.2 sequences: isoleucine67(ATC) instead of phenylalanine67(TTC) in DRw8/Dw8.1 and serine57(AGC) instead of aspartic acid57(GAT) in DRw8/Dw8.2. On the other hand the DR8.1 and DRw8/Dw8.3 have the same amino acid sequence although one silent nucleotide substitution has occurred between the two sequences. These results indicate that Japanese DR8.1 specificity corresponds to DRw8/Dw8.3. Furthermore, an oligonucleotide probe specific for this sequence was synthesized and hybridized with 33 HLA-typed controls. This probe clearly distinguished the particular subtype from other DRw8 subtypes and specificities.

Polymorphism of the fourth component of human complement (C4) was investigated in Japanese using an agarose gel electrophoresis and a slab polyacrylamide gel electrophoresis followed by immunofixation. Three common phenotypes were observed corresponding to the types F, FS and S reported in Europeans. Typing of the family material consisting of 48 matings with 96 offsprings showed no discrepancy from the postulate that C4 polymorphism is controlled by a pair of codominant alleles. In a sample from 291 unrelated healthy Japanese, the allele frequencies ofC4F andC4S are estimated at 0.543 and 0.457, respectively.

A total of 869 blood samples collected in Ishigaki Island were tested for 9 blood groups-ABO, MNSs, Rh, Q, Lewis, Duffy, Kell, Kidd and Diego blood groups, and the following results were obtained.The O gene frequency (γ) of the ABO blood groups was considerably higher than that of the Japanese, and the distribution of MNSs groups appeared to be different from it.The incidence of Rh negative individuals was 1.04%, which was intermediate between those of the Japanese and Ainu.The frequency of gene Jka was estimated at 0.1977, which was considerably lower than that of the Japanese.The incidence of Di (a+) type individuals was 6.45%.Genetic distance analysis was carried out to approach the estimation of genetic similarity between the populations.The results indicated that the in-habitants of Ishigaki Island were considerably different from the Ryukyuans of Miyako and Okinawa, though they were more similar to the latter than to the Japanese of Honshu, so far as the data of the 9 blood group systems are con-cerned.The relationships to the Ainu could not unequivocally be demonstrated.The population groups of the Japanese islands dealt with in the present study were equally far apart from the European.

The prevalence of human T-lymphotropic retrovirus type-1 (HTLV-1) was examined in the Asian Pacific area to search for endemic foci outside Japan. A total of 1323 sera from healthy subjects in the Philippines including Filipino lowlanders, Mongoloid slash-and-burn agriculturalists and the Mongoloid aboriginal hunter-gatherers (Aeta group and Mamanwa group) were examined for the presence of antibodies to HTLV-1 by the indirect immunofluorescence test and by the Western blot technique using HTLV-1 carrying cells. Nineteen out of 20 HTLV-1 antibody carriers found in the present study are clustered in the Aeta group of Mongoloid aboriginal hunter-gatherers who have until recently been isolated in the remote mountainous areas of Luzon Island since their arrival in the Philippines during the last glacial era (12,000-15,000 years ago). This finding supports the theory that HTLV-1 originated in Mongoloid racial groups during prehistoric times.

We investigated polymorphisms of complement components C2, C4, and factor B (BF) in Japanese patients with rheumatoid arthritis (RA). The frequencies of C4AQ0 (32.1%) and C4B5 (35.9%) among RA patients were significantly higher than among healthy control subjects. C4B5 was strongly associated with HLA-Bw54, Bw59, DR4.1, and DQw4. C4AQ0 showed no association with HLA-Bw54 or Bw59, but there was weak association with HLA-DR4.1 and DQw4. The number of persons with both C4AQ0 and C4B5 was significantly higher in the RA patient group (relative risk 13.5). C2C and BFS were the most common alleles in RA patients, as well as in healthy control subjects. These data support the existence of 2 different putative susceptibility haplotypes (HLA-Bw54 or Bw59;C2C; BFS;C4A3;C4B5;DR4.1;DQw4 and C2C;BFS; C4AQ0;C4B1 or C4B2) in Japanese patients with RA.

C7 polymorphism was investigated in a Japanese population (Tokyo). The C7 protein concentrations and hemolytic C7 activities in the serum samples of various phenotypes were measured by radial immuno-diffusion (RID) and radial diffusion hemolysis (RDH). The mean C7 protein levels for the common phenotypes C7 1, C7 2-1, C7 3-1, and C7 4-1 were 88%, 103%, 63%, and 94% of a standard, while the mean C7 activity levels were 96%, 90%, 63%, and 74%, respectively. Both the protein and the activity levels for C7 3-1 were significantly lower than those determined for the most common phenotype C7 1. The mean levels in two individuals of C7 3 phenotype were only 34% in protein concentration and 47% in functional activity. Concerning the ratio of functional to immunochemical C7 (i.e. the relative specific activity), there was no difference between the phenotypes C7 1 and C7 3-1. On the other hand, the mean hemolytic activity and the relative specific activity for C7 4-1 were significantly lower than those for C7 1.

Polymorphism of the properdin factor B (BF) was investigated using an agarose gel immunofixation electrophoresis in 487 unrelated healthy adult Japanese who were already typed for HLA-A, -B, -C and C2. Besides the previously reported phenotypes in Japanese (S, FS, and F), a rare heterozygous phenotype (tentatively maned FTS) was observed once. The estimated allele frequencies for BS*S, BF*F, and FB*FT (F Tokyo) were 0.801, 0.198, and 0,001 respectively. The relative electrophoretic mobility of the variant band of type FTS was measured by Dr. G Mauff to be F 0.75. The conversion fragment Bb of the type showed a double-banded pattern. BF hemolytic activity of the FTS individual was at the same level as other phenotypes. Statistical tests for the phenotypic data of BF with HLA-A, -B, -C, and C2 indicated the presence of the following significant associations in Japanese: Aw33-BF*F, A11-BF*S, Aw24-BF*S, B15-BF*F, B17-BF*F, Bw44-BF*F, B7-BF*S, Bw52;-BF*S, BW54-BF*S, BW59-BF*S, Cw3-BF*F, C2*AT-BF*F, and C2*A'-BF*F.

Variations in the mitochondrial DNA of a total of 150 cynomolgus monkeys (Macaca fascicularis) from Indonesia, the Philippines, and Malaysia were studied using a restriction endonuclease, EcoRI. Three distinct patterns were detected and they were denoted as morph 1, 2, and 3. The Malaysian population proved to be significantly different from the remaining two populations in the distributions of the three EcoRI morphs.

Restriction enzyme fragment patterns of human mitochondrial DNA (mtDNA) were analyzed using total DNAs from the blood cells of 122 Japanese (Ainu and Non-Ainu) living in Hokkaido, northern Japan. Polymorphisms were detected and the mtDNAs were classified into eleven types using four enzymes,AvaII,HincII,HpaI andPvuII. The distribution of the mtDNA morphs was not significantly different between the Ainu and the Non-Ainu samples, supporting the views that the Ainu are genetically one of the Mongoloid populations.

Polymorphism of the second component of human complement (C2) was investigated in a total of 292 sera from unrelated adult Japanese using a slab polyacrylamide gel isoelectric focusing followed by a specific hemolytic assay. Besides the common phenotype (C), two relatively infrequent double-banded phenotypes (AC and BC) were observed, which were considered to be heterozygotes. The estimated frequencies for the common allele,C2 C , and the variant alleles,C2 A andC2 B , were 0.937, 0.046, and 0.017, respectively. 229 samples were further typed for HLA-A, HLA-B, and HLA-C, and the result indicated the prescence of significant association ofC 2A withHLA-B15. This finding suggests that in Japanese there is an allelic combination showing linkage disequilibrium between C2 and HLA loci which is different from those in Caucasians.

Genetic polymorphism of human plasminogen in Japanese was investigated in 373 plasma samples from blood donors using polyacrylamide gel isoelectric focusing followed by immunofixation. It was confirmed that two alleles which had not been described in Caucasoid and Negroid populations exist in Japanese. The correspondence of the alleles thus far described also was examined by comparison runs. As a result, it was revealed thatPLG2′ described by Nakamuraet al. (1980a) is identical withPLG2 described by Nishimukaiet al. (1981) and thatPLGC reported as a rare variant by Nishimukaiet al. (1982) corresponds toPLG2 described by Hobart (1979). Allele frequencies were estimated as follows:PLGN*1=0.958,PLGN*2=0.004,PLGN*3=0.023,PLGN*4=0.015.