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N Takahata

Publications and source records attributed to N Takahata.

At least 19 recordsLinked to original sources
PubMed2006

Comparative analysis of human masculinity.

To study rapidly evolving male specific Y (MSY) genes we retrieved and analyzed nine such genes. VCY, HSFY and RBMY were found to have functional X gametologs, but the rest did not. Using chimpanzee orthologs for XKRY, CDY, HSFY, PRY, and TSPY, the average silent substitution is estimated as 0.017 +/- 0.006/site and the substitution rate is 1.42 x 10(-9)/site/year. Except for VCY, all other loci possess two or more pseudogenes on the Y chromosome. Sequence differences from functional genes show that BPY2, DAZ, XKRY, and RBMY each have one pseudogene for each one that is human specific, while others were generated well before the human-chimpanzee split, by means of duplication, retro-transposition or translocation. Some functional MSY gene duplication of VCY, CDY and HSFY, as well as X-linked VCX and HSFX duplication, occurred in the lineage leading to humans; these duplicates have accumulated nucleotide substitutions that permit their identification.

Animals↗
PubMed2004

The distribution of the ancestral haplotype in finite stepping-stone models with population expansion.

Recent extensive analyses of human DNA polymorphism reveal that the ancestral haplotype at various genetic loci occurs almost exclusively in African samples. We develop a coalescence-based simulation method in stepping-stone models with population expansion and examine the probability (P(A)) that the ancestral haplotype is found in African samples and the probability (Q(A)) that the most recent common ancestor of sampled genes occurs in Africa. These probabilities and other summary statistics are used to infer the human demographic history. It is shown that the high observed P(A) value cannot be explained simply by sampling bias. Rather, it suggests that the African population has been more strongly subdivided and isolated from each other than the non-African population and that there must have been some African populations which were not directly involved in the Out-of-Africa expansion in the late Pleistocene.

Africa↗
PubMed2003

Impairment of G(salpha) function in human brain cortex of Alzheimer's disease: comparison with normal aging.

We examined the quantity and quality of G proteins in membrane preparations of post-mortem human brain, i.e. in parietal, temporal and occipital cortical regions, from normal subjects over age (17-89 years old) and with Alzheimer's disease (AD) in comparison with aged-matched controls. In normal aging, the immunoreactivities determined of G(ialpha), G(qalpha) and G(beta) were inversely correlated with age. The function of G proteins was examined by photoaffinity GTP analogue [azidoanilido GTP (AAGTP)] labelling. AAGTP labelling to G(salpha) and G(i/oalpha), and the ratio of G(salpha) to G(i/oalpha) AAGTP labelling showed no age-dependent changes. In AD compared to age-matched controls, there were no significant differences in the levels of G(sHalpha), G(sLalpha), G(ialpha), G(oalpha), G(qalpha) and G(beta) subunits. Functional effects of G proteins, however, as measured by AAGTP labelling to G(salpha), but not to G(i/oalpha), was significantly decreased in AD compared to controls in the parietal and temporal cortex, but not in the occipital cortex. These results suggest that the disturbances of post-receptor trans-membrane signalling in AD can be attributed to functional changes of G(salpha), and these are independent of alterations in the level for those proteins in normal aging.

Adolescent↗
PubMed2001

Alu-mediated inactivation of the human CMP- N-acetylneuraminic acid hydroxylase gene.

Inactivation of the CMP-N-acetylneuraminic acid hydroxylase gene has provided an example of human-specific genomic mutation that results in a widespread biochemical difference between human and nonhuman primates. We have found that, although a region containing a 92-bp exon and an AluSq element in the hydroxylase gene is intact in all nonhuman primates examined, the same region in the human genome is replaced by an AluY element that was disseminated at least one million years ago. We propose a mechanistic model for this Alu-mediated replacement event, which deleted the 92-bp exon and thus inactivated the human hydroxylase gene. It is suggested that Alu elements have played potentially important roles in genotypic and phenotypic evolution in the hominid lineage.

Alu Elements↗
PubMed2001

Integrative study on chromosome evolution of mammals, ants and wasps based on the minimum interaction theory.

There is well-known evidence that in many eukaryotes, different species have different karyotypes (e.g. n=1-47 in ants and n=3-51 in mammals). Alternative (fusion and fission) hypotheses have been proposed to interpret this chromosomal diversity. Although the former has long been accepted, accumulating molecular genetics evidence seems to support the latter. We investigated this problem from a stochastic viewpoint using the Monte Carlo simulation method under the minimum interaction theory. We found that the results of simulations consistently interpreted the chromosomal diversity observed in mammals, ants and wasps, and concluded that chromosome evolution tends to evolve as a whole toward increasing chromosome numbers by centric fission. Accordingly, our results support the fission hypothesis. We discussed the process of chromosome evolution based on the latest theory of the molecular structure of chromosomes, and reconfirmed that the fission burst is the prime motive force in long-term chromosome evolution, and is effective in minimizing the genetic risks due to deleterious reciprocal translocations and in increasing the potential of genetic divergence. Centric fusion plays a biological role in eliminating heterochromatin (C-bands), but is only a local reverse flow in contrast to the previously held views.

Animals↗
PubMed2001

Testing multiregionality of modern human origins.

In order to examine the possibility of multiple founding populations of anatomically modern Homo sapiens, we collected DNA sequence data from 10 X-chromosomal regions, 5 autosomal regions, and 1 Y-chromosomal region, in addition to mitochondrial DNA. Except for five regions which are genealogically uninformative and two other regions for which chimpanzee orthologs are not available, the ancestral sequence and population for each of the remaining regions were successfully inferred. Of these 10 ancestral sequences, 9 occurred in Africa and only 1 occurred in Asia during the Pleistocene. Computer simulation was carried out to quantify the multiregional hypothesis based solely on the premise that there was more than one founding population in the Pleistocene. Allowing the breeding size to vary among the founding populations, the hypothesis may account for the observed African ancestry in 90% of the genomic regions. However, it is required that the founding population in Africa was much larger than that outside Africa. Likelihood estimates of the breeding sizes in the founding populations were more than 9,000 in Africa and less than 1,000 in outside of Africa, although these estimates can be much less biased at the 1% significance level. If the number of African ancestral sequences further increases as more data accumulate in other genomic regions, the conclusion of a single founding population of modern H. sapiens is inevitable.

Africa↗
PubMed2000

The origin and age of haplochromine fishes in Lake Victoria, east Africa.

According to a widely held view, the more than 300 species of haplochromine cichlid fishes in Lake Victoria (LV), East Africa, originated from a single founder species in less than 12,000 years. This view, however, does not follow from the published geological and molecular evidence. The former does indeed suggest that the LV basin dried out less than 15,000 years ago, but it does not provide any information about the species that re-colonized the new lake or that remained in the rivers draining the area. The molecular evidence is inconclusive with respect to the origin of the LV haplochromines because cichlids from critical regions around LV were not adequately sampled; and as far as the age of the LV haplochromines is concerned, it in fact led to an estimate of 250,000-750,000 years old. In the present study, mitochondrial DNA (control region) variation was determined by heteroduplex and sequencing analyses of more than 670 specimens collected at widely distributed East African riverine and lacustrine localities. The analyses revealed the existence of seven haplogroups (I-VII) distinguishable by characteristic substitutions. All endemic LV samples tested fell into one of these haplogroups (V) which, however, was also found to be present at various other localities, both riverine and lacustrine, outside LV. Within this haplogroup, four subgroups (VA through VD) could be distinguished, two of which (VB and VC) were represented in LV and at other localities. The great majority of the LV haplochromine species could be classified as belonging to the VC subgroup, which was found only in LV and in the rivers draining into it. Hence, while the endemic haplochromine species of LV could not have originated from a single founding population, the lake does harbour a large species flock which probably arose in situ.

Africa, Eastern↗
PubMed2000

DNA archives and our nearest relative: the trichotomy problem revisited.

Ever since Thomas H. Huxley correctly identified the chimpanzee and the gorilla as the two closest relatives of the human, the problem of the relationship among the three species ("the trichotomy problem") has remained unresolved. Comparative morphology and other classical methods of biological investigation have failed to answer definitively whether the chimpanzee or the gorilla is the closest relative of the human species. DNA sequences, both mitochondrial and nuclear, too, have provided equivocal solutions, depending on the region of the genome analyzed. Random sorting of ancestral allelic lineages, sequence convergence, and sequence exchanges between alleles or duplicated loci have been identified as likely factors confounding the interpretation of the interrelationships among the three species. In the present study most of these difficulties are overcome by identifying evolutionary causes that might potentially provide misleading information. Altogether, 45 loci consisting of 46, 855 bp are analyzed. About 60% of the loci and approximately the same proportion of phylogenetically informative sites support the human-chimpanzee clade. The remaining 40% of loci and sites support the two alternatives equally. It is demonstrated that, while incompatibility between loci can be explained by random sorting of allelic lineages, incompatibility within loci must be attributed largely to the joint effect of recombination and genetic drift. The trichotomy problem can be properly addressed only within this framework.

Alleles↗
PubMed2000

Mhc class II B gene evolution in East African cichlid fishes.

A distinctive feature of essential major histocompatibility complex (Mhc) loci is their polymorphism characterized by large genetic distances between alleles and long persistence times of allelic lineages. Since the lineages often span several successive speciations, we investigated the behavior of the Mhc alleles during or close to the speciation phase. We sequenced exon 2 of the class II B locus 4 from 232 East African cichlid fishes representing 32 related species. The divergence times of the (sub)species ranged from 6,000 to 8.4 million years. Two types of evolutionary analysis were used to elucidate the pattern of exon 2 sequence divergence. First, phylogenetic methods were applied to reconstruct the most likely evolutionary pathways leading from the last common ancestor of the set to the extant sequences, and to assess the probable mechanisms involved in allelic diversification. Second, pairwise comparisons of sequences were carried out to detect differences seemingly incompatible with origin by nonparallel point mutations. The analysis revealed point mutations to be the most important mechanism behind allelic divergences, with recombination playing only an auxiliary part. Comparison of sequences from related species revealed evidence of random allelic (lineage) losses apparently associated with speciation. Sharing of identical alleles could be demonstrated between species that diverged 2 million years ago. The phylogeny of the exon was incongruent with that of the flanking introns, indicating either a high degree of convergent evolution at the peptide-binding region-encoding sites, or intron homogenization.

Amino Acid Sequence↗
PubMed2000

Helium flux from a sedimentary basin.

The tritium-3He ages of groundwaters collected from the Saijo Basin in Japan were measured. The ages vary between 11.7 and 16.3 years. The 4He flux of >3 x 10(4) atoms/cm2 s is calculated by the 4He concentrations and ages. In addition the helium flux of 8.3 x 10(5) atoms/cm2 s is calculated at the Higashi-Niigata gas field in Japan. The above two estimates are consistent with the continental helium flux reported in the literature, suggesting that helium flux on the Earth's crust is uniform.

Geologic Sediments↗
PubMed1999

Evolution of Mhc-DRB introns: implications for the origin of primates.

Introns are generally believed to evolve too rapidly and too erratically to be of much use in phylogenetic reconstructions. Few phylogenetically informative intron sequences are available, however, to ascertain the validity of this supposition. In the present study the supposition was tested on the example of the mammalian class II major histocompatibility complex (Mhc) genes of the DRB family. Since the Mhc genes evolve under balancing selection and are believed to recombine or rearrange frequently, the evolution of their introns could be expected to be particularly rapid and subject to scrambling. Sequences of intron 4 and 5 DRB genes were obtained from polymerase chain reaction-amplified fragments of genomic DNA from representatives of six eutherian orders-Primates, Scandentia, Chiroptera, Dermoptera, Lagomorpha, and Insectivora. Although short stretches of the introns have indeed proved to be unalignable, the bulk of the intron sequences from all six orders, spanning >85 million years (my) of evolution, could be aligned and used in a study of the tempo and mode of intron evolution. The analysis has revealed the Mhc introns to evolve at a rate similar to that of other genes and of synonymous sites of non-Mhc genes. No evidence of homogenization or large-scale scrambling of the intron sequences could be found. The Mhc introns apparently evolve largely by point mutations and insertions/deletions. The phylogenetic signals contained in the intron sequences could be used to identify Scandentia as the sister group of Primates, to support the existence of the Archonta superorder, and to confirm the monophyly of the Chiroptera.

Animals↗
PubMed1999

Eye-head coordination abnormalities and regional cerebral blood flow in Alzheimer's disease.

1. Three patients with Alzheimer's disease (AD) and three healthy controls (HC) were examined for eye-head coordination. Regional cerebral blood flow (rCBF) was measured in AD patients. 2. Eye-head coordination was analyzed using a Vision analyzer, and magnetic sensors. The authors measured the rCBF with 123I-IMP, and 99mTc-ECD SPECT. 3. AD reduced gaze accuracy and head movements, and prolonged the latency of saccade as compared to HC. AD patients had a tendency to focus on the target by using eye movements only. 4. AD reduced the rCBF in the inferior parietal part and the visual area, relative to the motor area. Damage of these areas may have caused the eye-head coordination disorders in the AD patients.

Adult↗
PubMed1999

Alterations of tubulin function caused by chronic antidepressant treatment in rat brain.

1. Antidepressants have been used clinically for many years; however, the neurochemical mechanism for their therapeutic effect has not been clarified yet. Recent reports indicate that chronic antidepressant treatment directly affects the postsynaptic membrane to increase the coupling between the stimulatory GTP-binding (G) protein, Gs, and adenylyl cyclase. Tubulin, a cytoskeletal element, is involved in the stimulatory and inhibitory regulation of adenylyl cyclase in rat cerebral cortex via direct transfer of GTP to G proteins. In this study, we investigated whether the functional change of the adenylyl cyclase system caused by chronic antidepressant treatment involves an alteration of tubulin function in the regulation of adenylyl cyclase activity. 2. Male Sprague-Dawley rats were treated once daily with amitriptyline or saline by intraperitoneal injection (10 mg/kg) for 21 days, and their cerebral cortex membranes and GppNHp-liganded tubulin (tubulin-GppNHp) were prepared for what. 3. GppNHp-stimulated adenylyl cyclase activity in cortex membranes from amitriptyline-treated rats was significantly higher than that in control membranes. Furthermore, tubulin-GppNHp prepared from amitriptyline-treated rats was more potent than that from control rats in the stimulation of adenylyl cyclase activity in the cortex membranes of the controls. However, there was no significant difference in manganese-stimulated adenylyl cyclase activity between control and amitriptyline-treated rats. 4. The present results suggest that chronic antidepressant treatment enhances not only the coupling between Gs and the catalytic subunit of adenylyl cyclase but also tubulin interaction with Gs in the cerebral cortex of the rat.

Adenylyl Cyclases↗
PubMed1999

Molecular clock and recombination in primate Mhc genes.

To set an accurate chronological framework to the evolution of primate class I and II genes in the major histocompatibility complex (Mhc), the rate of silent nucleotide substitutions in exons and introns is examined for various cDNA and genome sequences currently available. The rate is sensitive to the GC content and correlates negatively with increased GC biases at the third codon positions of Mhc genes. The intergenic recombination rate in the HLA region is estimated from the synonymous nucleotide differences at 37 linked loci. Any HLA subregion is recombined more or less at the ordinary rate of 1 cM per 1 Mb, although the rate may be reduced in some subregions. This information is used to discuss HLA haplotypes when they are applied to studies of human demography. The unusual polymorphism in the alpha-helix of HLA-DRB1 is also revisited in relation to intragenic recombination, but the molecular mechanism and the evolutionary cause both remain enigmatic.

Animals↗
PubMed1999

Paleo-demography of the Drosophila melanogaster subgroup: application of the maximum likelihood method.

The species divergence times and demographic histories of Drosophila melanogaster and its three sibling species, D. mauritiana, D. simulans, and D. yakuba, were investigated using a maximum likelihood (ML) method. Thirty-nine orthologous loci for these four species were retrieved from DDBJ/EMBL/GenBank database. Both autosomal and X-linked loci were used in this study. A significant degree of rate heterogeneity across loci was observed for each pair of species. Most loci have the GC content greater than 50% at the third codon position. The codon usage bias in Drosophila loci is considered to result in the high GC content and the heterogenous rates across loci. The chi-square, G, and Fisher's exact tests indicated that data sets with 11, 23, and 9 pairs of DNA sequences for the comparison of D. melanogaster with D. mauritiana, D. simulans, and D. yakuba, respectively, retain homogeneous rates across loci. We applied the ML method to these data sets to estimate the DNA sequence divergences before and after speciation of each species pair along with their standard deviations. Using 1.6 x 10(-8) as the rate of nucleotide substitutions per silent site per year, our results indicate that the D. melanogaster lineage split from D. yakuba approximately 5.1 +/- 0.8 million years ago (mya), D. mauritiana 2.7 +/- 0.4 mya, and D. simulans 2.3 +/- 0.3 mya. It implies that D. melanogaster became distinct from D. mauritiana and D. simulans at approximately the same time and from D. yakuba no earlier than 10 mya. The effective ancestral population size of D. melanogaster appears to be stable over evolutionary time. Assuming 10 generations per year for Drosophila, the effective population size in the ancestral lineage immediately prior to the time of species divergence is approximately 3 x 10(6), which is close to that estimated for the extant D. melanogaster population. The D. melanogaster did not encounter any obvious bottleneck during the past 10 million years.

Animals↗
PubMed1998

Persistence of neutral polymorphisms in Lake Victoria cichlid fish.

Phylogenetic trees for groups of closely related species often have different topologies, depending on the genes used. One explanation for the discordant topologies is the persistence of polymorphisms through the speciation phase, followed by differential fixation of alleles in the resulting species. The existence of transspecies polymorphisms has been documented for alleles maintained by balancing selection but not for neutral alleles. In the present study, transspecific persistence of neutral polymorphisms was tested in the endemic haplochromine species flock of Lake Victoria cichlid fish. Putative noncoding region polymorphisms were identified at four randomly selected nuclear loci and tested on a collection of 12 Lake Victoria species and their putative riverine ancestors. At all loci, the same polymorphism was found to be present in nearly all the tested species, both lacustrine and riverine. Different polymorphisms at these loci were found in cichlids of other East African lakes (Malawi and Tanganyika). The Lake Victoria polymorphisms must have therefore arisen after the flocks now inhabiting the three great lakes diverged from one another, but before the riverine ancestors of the Lake Victoria flock colonized the Lake. Calculations based on the mtDNA clock suggest that the polymorphisms have persisted for about 1.4 million years. To maintain neutral polymorphisms for such a long time, the population size must have remained large throughout the entire period.

Actins↗
PubMed1998

The neutral theory and natural selection in the HLA region.

Based on available DNA sequence data in the HLA region of 4 Mb, we review the degree of polymorphism at 39 loci of which most are involved in the immune system. The extent of nucleotide differences per silent site differs greatly from locus to locus. It is exceptionally high at classical MHC loci, intermediate at six MHC-related pseudogenes as well as at some loci in class I and II regions, and low in the class III region. Different exons of individual MHC loci show also different degrees of silent polymorphism; high in the exons encoding for the peptide binding region (PBR) and low in the exons encoding for trans-membranes and cytoplasmic tails. The degree of polymorphism within MHC allelic lineages is not much smaller than that between allelic lineages, contrary to the expectation where intra-allelic sequence exchanges are restricted. The observation that many allelic lineages at the HLA-DRB1 locus are combinations of distinct motifs in the beta pleated sheet and alpha helix of PBR indicates that sequence exchanges occur even within exon 2. Semi-quantitative analysis is presented about the rate of sequence exchanges between selected and linked neutral regions, although more sequence information is necessary to make definite conclusions. The extraordinary MHC polymorphism is viewed from the dual function of MHC molecules that controls the acquired immune system.

Alleles↗