Shintaroh Ueda

Molecular Genetic Analysis of Remains of a 2,000-Year-Old Human Population in China—and Its Relevance for the Origin of the Modern Japanese Population

We extracted DNA from the human remains excavated from the Yixi site ( approximately 2,000 years before the present) in the Shandong peninsula of China and, through PCR amplification, determined nucleotide sequences of their mitochondrial D-loop regions. Nucleotide diversity of the ancient Yixi people was similar to those of modern populations. Modern humans in Asia and the circum-Pacific region are divided into six radiation groups, on the basis of the phylogenetic network constructed by means of 414 mtDNA types from 1, 298 individuals. We compared the ancient Yixi people with the modern Asian and the circum-Pacific populations, using two indices: frequency distribution of the radiation groups and genetic distances among populations. Both revealed that the closest genetic relatedness is between the ancient Yixi people and the modern Taiwan Han Chinese. The Yixi people show closer genetic affinity with Mongolians, mainland Japanese, and Koreans than with Ainu and Ryukyu Japanese and less genetic resemblance with Jomon people and Yayoi people, their predecessors and contemporaries, respectively, in ancient Japan.

Class III POU Genes: Generation of Homopolymeric Amino Acid Repeats Under GC Pressure in Mammals

The class III POU transcription factor genes play an important role in the nervous system. Comparison of their entire amino acid sequences disclosed a remarkable feature of particular mammalian class III POU genes. Alanine, glycine, and proline repeats were present in the mammalian Brain-1 gene, whereas most of these repeats were absent in the nonmammalian homologue. The mammalian Brain-2 gene had alanine, glycine, proline, and glutamine repeats, which were missing in the nonmammalian homologue. The mammalian Scip gene had alanine, glycine, proline, and histidine repeats, but the nonmammalian homologue completely lacked these repeats. In contrast, the mammalian Brain-4 gene had no amino acid repeats like its nonmammalian homologue. The mammalian genes containing the characteristic amino acid repeats had another feature, higher GC content. We found a positive correlation between the GC content and the amino acid repeat ratio. Those amino acids were encoded by triplet codons with relatively high GC content. These results suggest that the GC pressure has facilitated generation of the homopolymeric amino acid repeats.

Evolutionary hypervariability in the hinge region of the immunoglobulin alpha gene

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.

Nucleotide sequences of immunoglobulin-epsilon pseudogenes in man and apes and their phylogenetic relationships☆

To understand the phylogenetic relationships between hominoids, the nucleotide sequences of immunoglobulin-epsilon processed pseudogenes from chimpanzee, gorilla and orangutan were determined. The basic structures of these processed pseudogenes agreed with their human counterpart. Although the degrees of nucleotide differences between man and the African apes had no statistical significance, all the analytical data examined supported the theory that chimpanzee is the closest relative of man. This result was consistent with that deduced by our recent qualitative study. Studies on the nucleotide sequences of globin genes have suggested that the molecular clock runs more slowly in hominoids than in non-hominoid primates. According to the present data, however, further retardation of the evolutionary rate was not observed in the human lineage. Assuming that orangutan diverged 14 million years ago and that the evolutionary rate between the orangutan lineage and the lineage leading to the other three species is constant, the divergence dates of chimpanzee and gorilla were estimated to be 4.9(+/- 0.9) and 5.9(+/- 0.9) million years ago, respectively.

Multiple recombinational events in primate immunoglobulin epsilon and alpha genes suggest closer relationship of humans to chimpanzees than to gorillas

SummaryImmunoglobulin epsilon and alpha genes of chimpanzee and gorilla were isolated and their structures were compared with their human counterparts. Multiple deletions and duplications seem to have happened in both genes during hominoid evolution; the chimpanzee had deleted the entire Cε2 gene after its divergence. In addition, the length of the Cα1 hinge region of gorilla is distinct from those of chimpanzee and humans. Structural homology of the epsilon and alpha genes suggests that humans are evolutionarily closer to chimpanzees than to gorillas.

Genetic diversity and evolutionary relationships in genus Oryza revealed by using highly variable regions of chloroplast DNA.

We studied the phylogeny of the genus Oryza using chloroplast DNA sequences. To identify regions containing sufficient variation for elucidating the relationship of closely related species with fine resolution and high reliability, we first compared the complete chloroplast sequences of Oryza sativa japonica, O. sativa indica, and O. nivara, and identified regions containing many variant sites. Nucleotide sequences of the variant regions were newly determined in 19 Oryza species including 58 cultivated and wild strains. An in silico pre-analysis of the whole chloroplast genome and subsequent nucleotide sequencing of the regions with the greatest number of variant sites, which were disclosed to be hot spots by the in silico pre-analysis, enabled us to examine genetic diversity in the genus Oryza with excellent resolution. Based on phylogenetic trees constructed using highly diverged regions in the chloroplast genome, we discuss the maternal relationships among Oryza species.

The neuronal POU transcription factor Brn-2 interacts with Jab1, a gene involved in the onset of neurodegenerative diseases.

Brain-2 (Brn-2), a Class III POU transcription factor, plays an important role in the development of the neocortex and the establishment of neural cell lineage. Here we performed a yeast two-hybrid screening to identify the Brn-2 binding proteins. We obtained Jun-activation-domain-binding protein 1 (Jab1) as a new Brn-2 binding protein. Direct interaction between Brn-2 and Jab1 was confirmed by using a surface plasmon resonance biosensor. Considering the involvement of Jab1 in the onset of the neurodegenerative disorders such as Parkinsons disease and Alzheimers disease, the interaction between Brn-2 and Jab1 may provide some insights into the understanding of neuronal development and neurodegenerative diseases.

Genomic organization and alternative transcripts of the human PQBP-1 gene

PQBP-1 has been identified as a protein that binds to huntingtin, androgen receptor and transcription factor Brain-2 through their homopolymeric glutamine repeats. We here report the genomic organization of the human PQBP-1 gene and its multiple alternative transcripts. The coding region of PQBP-1 comprises six exons and five introns, and four types of alternative transcript, designated PQBP-1a to PQBP-1d, were found in addition to the PQBP-1 transcript reported originally. All of the PQBP-1 transcripts retain the WW domain in the N-terminal region, a potent transactivator domain. On the other hand, there is a wide variation in their C-terminal regions. Importantly, PQBP-1a and PQBP-1d lack the domain responsible for the interaction with homopolymeric glutamine repeats and a nuclear localization signal.

Genetic Study of the Paleolithic and Neolithic Southeast Asians

AbstractDNA samples were extracted from six prehistoric human remains, found on the Malay Peninsula, dating to the Paleolithic and the Neolithic periods. Nucleotide sequences of mitochondrial DNA were determined by the polymerase chain reaction-direct sequencing method. A phylogenetic tree between prehistoric and present humans was constructed based on the nucleotide sequence data. Mitochondrial DNA phylogenetic relationships and ethnoarchaeological evidence suggest that there is a continuity beetween the pre-Neolithic humans and the present Semang and that the Neolithic humans in this area might be an ancestral group of the Senoi.

The Unstable CCTG Repeat Responsible for Myotonic Dystrophy Type 2 Originates from an AluSx Element Insertion into an Early Primate Genome

Myotonic dystrophy type 2 (DM2) is a subtype of the myotonic dystrophies, caused by expansion of a tetranucleotide CCTG repeat in intron 1 of the zinc finger protein 9 (ZNF9) gene. The expansions are extremely unstable and variable, ranging from 75–11,000 CCTG repeats. This unprecedented repeat size and somatic heterogeneity make molecular diagnosis of DM2 difficult, and yield variable clinical phenotypes. To better understand the mutational origin and instability of the ZNF9 CCTG repeat, we analyzed the repeat configuration and flanking regions in 26 primate species. The 3′-end of an AluSx element, flanked by target site duplications (5′-ACTRCCAR-3′or 5′-ACTRCCARTTA-3′), followed the CCTG repeat, suggesting that the repeat was originally derived from the Alu element insertion. In addition, our results revealed lineage-specific repetitive motifs: pyrimidine (CT)-rich repeat motifs in New World monkeys, dinucleotide (TG) repeat motifs in Old World monkeys and gibbons, and dinucleotide (TG) and tetranucleotide (TCTG and/or CCTG) repeat motifs in great apes and humans. Moreover, these di- and tetra-nucleotide repeat motifs arose from the poly (A) tail of the AluSx element, and evolved into unstable CCTG repeats during primate evolution. Alu elements are known to be the source of microsatellite repeats responsible for two other repeat expansion disorders: Friedreich ataxia and spinocerebellar ataxia type 10. Taken together, these findings raise questions as to the mechanism(s) by which Alu-mediated repeats developed into the large, extremely unstable expansions common to these three disorders.