Biomedical subjects
Publications and source records attributed to N Saitou.
We determined 5 sequences of Japanese macaque ABO blood group gene exon 7 (ca. 0.5 kb) and 2 sequences for exon 5 and intron 6 (ca. 1.7 kb). We compared those data with published sequences of other Old World monkey species, and the results suggest that alleles A and B were polymorphic in the ancestral species of macaques, and that B type allele evolved independently in macaque and baboon lineages.
The amino acid sequence of Fuc-TIX is very highly conserved between mouse and human. The number of non-synonymous nucleotide substitutions of the Fuc-TIX gene between human and mouse was strikingly low, and almost equivalent to that of the alpha-actin gene. This indicates that Fuc-TIX is under a strong selective pressure of preservation during evolution. The human Fuc-TIX (hFuc-TIX) showed a unique characteristics, i.e. hFuc-TIX was not activated by Mn2+ and Co2+, whereas hFuc-TIV and hFuc-TVI were activated by the cations. The hFuc-TIX transcripts were abundantly expressed in brain and stomach, and interestingly were detected in spleen and peripheral blood leukocytes.
We isolated two new keratin cDNAs by screening a cDNA library constructed from poly(A)+ RNA of the dorsal and abdominal skin of C57BL/10J mice with a probe of human KRT14. Due to its high sequence homology to human keratin 17 cDNA, one full-length cDNA is most likely to be mouse keratin 17 (Krt1-17) cDNA. The other is the putative full-length cDNA of a novel type I keratin gene, designated Krt1-c29. These two keratin genes were mapped to the distal portion of Chromosome 11, where the mouse keratin gene complex-1 (Krt1) is localized. To elucidate the genomic organization of Krt1 in mice, we carried out genetic and physical analyses of Krt1. A large-scale linkage analysis using intersubspecific backcrosses suggested that there are two major clusters in Krt1, one containing Krt1-c29, Krt1-10, and Krt1-12 and the other containing Krt1-14, -15, -17, and -19. Truncation experiments with two yeast artificial chromosome clones containing the two clusters above have revealed that the gene order of Krt1 is centromere-Krt1-c29-Krt1-10-Krt1-12-Krt1-13-K rt1-15-Krt1-19-Krt1-14-K rt1-17-telomere. Finally, we analyzed sequence divergence between the genes belonging to the Krt1 complex. The results clearly indicated that genes are classified into two major groups with respect to phylogenetic relationship. Each group consists of the respective gene cluster demonstrated by genetic and physical analyses in this study, suggesting that the physical organization of the Krt1 complex reflects the evolutionary process of gene duplication of this complex.
There are two tightly linked loci (D and CE) for the human Rh blood group. Their gene products are membrane proteins having 12 transmembrane domains and form a complex with Rh50 glycoprotein on erythrocytes. We constructed phylogenetic networks of human and nonhuman primate Rh genes, and the network patterns suggested the occurrences of gene conversions. We therefore used a modified site-by-site reconstruction method by using two assumed gene trees and detected 9 or 11 converted regions. After eliminating the effect of gene conversions, we estimated numbers of nonsynonymous and synonymous substitutions for each branch of both trees. Whichever gene tree we selected the branch connecting hominoids and Old World monkeys showed significantly higher nonsynonymous than synonymous substitutions, an indication of positive selection. Many other branches also showed higher nonsynonymous than synonymous substitutions; this suggests that the Rh genes have experienced some kind of positive selection.
Pseudomonas syringae are differentiated into approximately 50 pathovars with different plant pathogenicities and host specificities. To understand its pathogenicity differentiation and the evolutionary mechanisms of pathogenicity-related genes, phylogenetic analyses were conducted using 56 strains belonging to 19 pathovars. gyrB and rpoD were adopted as the index genes to determine the course of bacterial genome evolution, and hrpL and hrpS were selected as the representatives of the pathogenicity-related genes located on the genome (chromosome). Based on these data, NJ, MP, and ML phylogenetic trees were constructed, and thus 3 trees for each gene and 12 gene trees in total were obtained, all of which showed three distinct monophyletic groups: Groups 1, 2 and 3. The observation that the same set of OTUs constitute each group in all four genes suggests that these genes had not experienced any intergroup horizontal gene transfer within P. syringae but have been stable on and evolved along with the P. syringae genome. These four index genes were then compared with another pathogenicity-related gene, argK (the phaseolotoxin-resistant ornithine carbamoyltransferase gene, which exists within the argK-tox gene cluster). All 13 strains of pv. phaseolicola and pv. actinidiae used had been confirmed to produce phaseolotoxin and to have argK, whose sequences were completely identical, without a single synonymous substitution among the strains used (Sawada et al. 1997a). On the other hand, argK were not present on the genomes of the other 43 strains used other than pv. actinidiae and pv. phaseolicola. Thus, the productivity of phaseolotoxin and the possession of the argK gene were shown at only two points on the phylogenetic tree: Group 1 (pv. actinidiae) and Group 3 (pv. phaseolicola). A t test between these two pathovars for the synonymous distances of argK and the tandemly combined sequence of the four index genes showed a high significance, suggesting that the argK gene (or argK-tox gene cluster) experienced horizontal gene transfer and expanded its distribution over two pathovars after the pathovars had separated, thus showing a base substitution pattern extremely different from that of the noncluster region of the genome.
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.
Muscle tissues can be divided into six classes; smooth, fast skeletal, slow skeletal and cardiac muscle tissues for vertebrates, and striated and smooth muscle tissues for invertebrates. We reconstructed phylogenetic trees of six protein genes that are expressed in muscle tissues and, using a newly developed program, inferred the phylogeny of muscle tissues by superimposition of five of those gene trees. The proteins used are troponin C, myosin essential light chain, myosin regulatory light chain, myosin heavy chain, actin, and muscle regulatory factor (MRF) families. Our results suggest that the emergence of skeletal-cardiac muscle type tissues preceded the vertebrate/arthropod divergence (ca. 700 MYA), while vertebrate smooth muscle seemed to evolve independent of other muscles. In addition, skeletal muscle is not monophyletic, but cardiac and slow skeletal muscles make a cluster. Furthermore, arthropod striated muscle, urochordate smooth muscle, and vertebrate muscles except for smooth muscle share a common ancestor. On the other hand, arthropod nonmuscle and vertebrate smooth muscle and nonmuscle share a common ancestor.
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Surname in China, as a cultural genetic factor, is a very huge and remarkable human population study resource. The transmission feature of surname has been proved to be similar to that of the genetic markers on Y chromosome of males. It, therefore, has been applied in the population genetic studies since 1965's. In the present study, we have analyzed a group of Chinese surname data of the Song dynasty (AD. 960-1179). The distribution of the present surname data is corresponded with the Karlin-McGregor's neutral allele model. The surname abundance alpha and the migration rate parameter v in the Song dynasty in 16 provincial regions reflected degrees of migration and admixture at that time. Surname phylogenetic dendrogram analysis demonstrated that the Han Chinese had been segregated into North and South two parts in Song dynasty of 1000 years ago. Wuyi and Nanling Mountains divided Northern and Southern Han populations into the two major parts of Han Chinese. The results also showed that the surname distribution of Song dynasty 1000 years ago was quite similar to the present model. The 100 high frequency surnames in Song dynasty were well corresponded with the current surname distribution. This phenomenon suggests that Chinese surnames have been steadily transmitted from ancient to the present. The present study improved that the Chinese surname is a very important genetic resource for the studies of structure of the Chinese populations, migration, and affinities among different populations.
We have sequenced the complete coding region of the Rh blood group gene for mouse and rat and that of Rh-related 50 kD glycoprotein (Rh50) for mouse, rat, and crab-eating macaque. Phylogenetic analyses of Rh and Rh50 amino acid sequences indicate that the Rh50 gene has been evolving about two times more slowly than the Rh blood group gene in both primates and rodents. This conservative nature of the Rh50 gene suggests its relative importance to the Rh blood group gene. The time of gene duplication that produced the Rh and Rh50 genes was estimated to be about 240-310 million years ago. We also conducted window analyses of synonymous and nonsynonymous nucleotide substitutions for those two genes. Some peaks where nonsynonymous substitutions are higher than synonymous ones were located on outer membrane regions. This suggests the existence of positive Darwinian selection on Rh and Rh50 genes through host-parasite interactions.
To evaluate factors that influence of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels in elderly people, we measured those levels in 54 men and 148 women (84.4 +/- 0.5 years old), and looked for associations of ANP and BNP with clinical factors and echocardiographic variables [left ventricular mass index and atrial to-early peak transmitral velocity ratio (A/E)]. ANP and BNP levels were 1.6 and 6.5 times higher than average. Sex was not a significant factor. We also looked for a link between cardiac rhythms and levels of ANP and BNP. Patients with atrial fibrillation had significantly higher levels of ANP and BNP than did patients with sinus rhythm. ANP and BNP levels were abnormally high in patients with left ventricular hypertrophy (LVH). We could measured A/E in 161 of 202 subjects; 154 of 157 subjects with normal LV systolic function had A/E > 1 which indicates abnormally low in LV diastolic function. Moreover, abnormally high LV diastolic stress might have been present, because 124 of 202 subjects had aortic regurgitation. We divided the patients into two groups: those 65 to 75 years old, and those over 75 years old. The older patients had significantly higher levels of ANP and BNP even without LVH and without a difference in renal function. Furthermore, the older patients had significantly higher levels of BNP even without LVH, with normal renal function, with sinus rhythm, with normal LV systolic function, and in NYHA Class I or II. These data indicate that ANP and BNP levels in people with senility may be associated with the cardiac rhythm and with abnormally low renal function, myocardial hypertrophy, abnormally high cardiac volume, and abnormally low diastolic function.
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.
There are three common alleles (A, B, and O) at the human ABO blood group locus. We compared nucleotide sequences of these alleles, and relatively large numbers of nucleotide differences were found among them. These differences correspond to the divergence time of at least a few million years, which is unusually large for a human allelic divergence under neutral evolution. We constructed phylogenetic networks of human and nonhuman primate ABO alleles, and at least three independent appearances of B alleles from the ancestral A form were observed. These results suggest that some kind of balancing selection may have been operating at the ABO locus. We also constructed phylogenetic trees of ABO and their evolutionarily related alpha-1,3-galactosyltransferase genes, and the divergence time between these two families was estimated to be roughly 400 MYA.
The phylogenetic relationship among the salmonid fishes of the genus Oncorhynchus has been analyzed using various kinds of markers for a long time. However, there are three major disagreements among those studies; (1) the authenticity of the Pacific salmon group as a monophyletic cluster, (2) the phylogenetic relationship among three Pacific salmons (pink salmon, sockeye salmon, and chum salmon), and (3) the phylogenetic position of masu salmon. We used allozyme electrophoresis to clarify the phylogenetic relationship between the Pacific salmon group and the Pacific trout group. Furthermore, we reanalysed published mitochondrial DNA D-loop sequences (Shedlock et al., 1992). Allozymic data and mtDNA data indicated the following consistent results; (1) all Pacific salmons formed a monophyletic cluster, (2) chum salmon and pink salmon were clustered within those Pacific salmons, (3) masu salmon formed a cluster with other Pacific salmons and diverged first in this group.
ABO is clinically the most important blood group system in transfusion medicine and includes many variant phenotypes. To understand the molecular genetic basis of this polymorphic system, we have analyzed genomic DNAs obtained from Japanese individuals possessing variant ABO phenotypes including A2, Ax, Ael, cis-AB, Bx, and Bel. By polymerase chain reaction-single-strand conformation polymorphism (SSCP) and nucleotide sequence analyses, we identified 11 different alleles. These alleles had nucleotide sequences different from those of the previously described 13 different alleles responsible for the common ABO phenotypes. Analysis of the nucleotide sequences of the alleles responsible for those variant phenotypes showed that the amino acid residues at position 266 and 268 may be crucial for transferase specificity, whereas those at positions 214, 216, 223, 291, and 352 may be critical for the activity level. Nine of the 11 alleles, responsible for the A2, Ax, Ael, cis-AB, Bx, and Bel phenotypes, were presumed to be generated from common ABO alleles by single nucleotide mutations such as nonsynonymous substitution, deletion, or insertion. Two other alleles, responsible for the A2 and Ael phenotypes, may have originated by recombination, gene conversionlike events or accumulation of nucleotide substitutions. Our data indicate that different alleles could cause the same ABO variant phenotypes, and that these alleles do not necessarily belong to a single evolutionary lineage.
Distribution of the p53 pseudogene within the house mouse species (genus Mus) was studied with polymerase chain reaction for 37 individuals that were caught at different localities. Pseudogene-specific fragments were detected in some, but not all, individuals of Mus musculus subspecies regardless of locality and type of subspecies. In addition, 3 of 7 individuals belonging to different Mus species carried the pseudogene in their genomes. These results show the existence of an interspecific presence/absence polymorphism of the p53 pseudogene in mice. Sequence analysis of 11 amplified 0.3-kb fragments suggested that the pseudogene originated in an ancestral mouse about 7 million years ago. Thus alleles with and without the p53 pseudogene have persisted through the mice speciation. The evolutionary rate for the p53 functional gene was also estimated to be about 3.3 x 10(-9) per nucleotide site per year.
Erythritol (20 g in solution) was administered orally in a single-dose to 5 patients with diabetes. Serum erythritol levels reached a peak 1 hr after administration and then declined rapidly. Total urinary excretion was 82.0 +/- 3.7% within 24 hr and 88.5 +/- 3.3% within 72 hr. Serum glucose and insulin levels remained unchanged until a meal was taken (3 hr after erythritol administration) and then increased. Free fatty acids and 3-hydroxybutyric acid levels increased after erythritol administration but dropped after ingestion of food. In a separate clinical trial, erythritol (20 g) was administered orally daily for 14 days to 11 patients with diabetes. Mean serum glucose and hemoglobin A1c levels decreased over the time period. Indices of renal function-blood urea nitrogen, creatinine, and beta 2-microglobulin-did not change significantly. The single dose study suggests that erythritol exerts no significant effects on the metabolism of diabetic patients. Two-week daily administration of erythritol had no adverse effect on blood glucose control.
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.