論文 - 新村 芳人
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Synchronized expansion and contraction of olfactory, vomeronasal, and taste receptor gene families in hystricomorph rodents 査読あり 国際共著
Yoshihito Niimura, Bhim B. Biswa, Takushi Kishida, Atsushi Toyoda, Kazumichi Fujiwara, Masato Ito, Kazushige Touhara, Miho Inoue-Murayama, Scott H. Jenkins, Christopher Adenyo, Boniface B. Kayang, Tsuyoshi Koide
Molecular Biology and Evolution 41 ( 4 ) msae071 2024年4月
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Chromosome-scale assembly with improved annotation provides insights into breed-wide genomic structure and diversity in domestic cats. 査読あり 国際共著
Matsumoto Y, Yik-Lok Chung C, Isobe S, Sakamoto M, Lin X, Chan TF, Hirakawa H, Ishihara G, Lam HM, Nakayama S, Sasamoto S, Tanizawa Y, Watanabe A, Watanabe K, Yagura M, Niimura Y, Nakamura Y
Journal of advanced research 2024年10月
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Genetic variation in the human olfactory receptor OR5AN1 associates with the perception of musks. 査読あり
Sato-Akuhara N, Trimmer C, Keller A, Niimura Y, Shirasu M, Mainland JD, Touhara K
Chemical Senses 48 bjac037 2023年1月
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Structural model for ligand binding and channel opening of an insect gustatory receptor. 査読あり
Morinaga S, Nagata K, Ihara S, Yumita T, Niimura Y, Sato K, Touhara K
The Journal of Biological Chemistry 298 ( 11 ) 102573 2022年10月
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Genetic variation of olfactory receptor gene family in a Japanese population. 査読あり 国際共著
Akhtar MS, Ashino R, Oota H, Ishida H, Niimura Y, Touhara K, Melin AD, Kawamura S
Anthropological Science 130 ( 2 ) 93 - 106 2022年7月
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The genomics of ecological flexibility, large brains, and long lives in capuchin monkeys revealed with fecalFACS. 査読あり 国際誌
Orkin JD, Montague MJ, Tejada-Martinez D, de Manuel M, Del Campo J, Cheves Hernandez S, Di Fiore A, Fontsere C, Hodgson JA, Janiak MC, Kuderna LFK, Lizano E, Martin MP, Niimura Y, Perry GH, Valverde CS, Tang J, Warren WC, de Magalhães JP, Kawamura S, Marquès-Bonet T, Krawetz R, Melin AD
Proceedings of the National Academy of Sciences of the United States of America 118 ( 7 ) 2021年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
Ecological flexibility, extended lifespans, and large brains have long intrigued evolutionary biologists, and comparative genomics offers an efficient and effective tool for generating new insights into the evolution of such traits. Studies of capuchin monkeys are particularly well situated to shed light on the selective pressures and genetic underpinnings of local adaptation to diverse habitats, longevity, and brain development. Distributed widely across Central and South America, they are inventive and extractive foragers, known for their sensorimotor intelligence. Capuchins have among the largest relative brain size of any monkey and a lifespan that exceeds 50 y, despite their small (3 to 5 kg) body size. We assemble and annotate a de novo reference genome for Cebus imitator Through high-depth sequencing of DNA derived from blood, various tissues, and feces via fluorescence-activated cell sorting (fecalFACS) to isolate monkey epithelial cells, we compared genomes of capuchin populations from tropical dry forests and lowland rainforests and identified population divergence in genes involved in water balance, kidney function, and metabolism. Through a comparative genomics approach spanning a wide diversity of mammals, we identified genes under positive selection associated with longevity and brain development. Additionally, we provide a technological advancement in the use of noninvasive genomics for studies of free-ranging mammals. Our intra- and interspecific comparative study of capuchin genomics provides insights into processes underlying local adaptation to diverse and physiologically challenging environments, as well as the molecular basis of brain evolution and longevity.
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Origin and Evolution of the Gene Family of Proteinaceous Pheromones, the Exocrine Gland-Secreting Peptides, in Rodents. 査読あり 国際誌
Niimura Y, Tsunoda M, Kato S, Murata K, Yanagawa T, Suzuki S, Touhara K
Molecular biology and evolution 38 ( 2 ) 634 - 649 2021年1月
担当区分：筆頭著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌）
The exocrine-gland secreting peptide (ESP)gene family encodes proteinaceous pheromones that are recognized by the vomeronasal organ in mice. For example, ESP1 is a male pheromone secreted in tear fluid that regulates socio-sexual behavior, and ESP22 is a juvenile pheromone that suppresses adult sexual behavior. The family consists of multiple genes and has been identified only in mouse and rat genomes. The coding region of a mouse ESP gene is separated into two exons, each encoding signal and mature sequences. Here, we report the origin and evolution of the ESP gene family. ESP genes were found only in the Muridea and Cricetidae families of rodents, suggesting a recent origin of ESP genes in the common ancestor of murids and cricetids. ESP genes show a great diversity in number, length, and sequence among different species as well as mouse strains. Some ESPs in rats and golden hamsters are expressed in the lacrimal gland and the salivary gland. We also found that a mature sequence of an ESP gene showed overall sequence similarity to the α-globin gene. The ancestral ESP gene seems to be generated by recombination of a retrotransposed α-globin gene with the signal-encoding exon of the CRISP2 gene located adjacent to the ESP gene cluster. This study provides an intriguing example of molecular tinkering in rapidly evolving species-specific proteinaceous pheromone genes.
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Comparative genomic analyses illuminate the distinct evolution of megabats within Chiroptera. 査読あり 国際誌
Nikaido M, Kondo S, Zhang Z, Wu J, Nishihara H, Niimura Y, Suzuki S, Touhara K, Suzuki Y, Noguchi H, Minakuchi Y, Toyoda A, Fujiyama A, Sugano S, Yoneda M, Kai C
DNA research : an international journal for rapid publication of reports on genes and genomes 27 ( 4 ) 2020年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
The revision of the sub-order Microchiroptera is one of the most intriguing outcomes in recent mammalian molecular phylogeny. The unexpected sister-taxon relationship between rhinolophoid microbats and megabats, with the exclusion of other microbats, suggests that megabats arose in a relatively short period of time from a microbat-like ancestor. In order to understand the genetic mechanism underlying adaptive evolution in megabats, we determined the whole-genome sequences of two rousette megabats, Leschenault's rousette (Rousettus leschenaultia) and the Egyptian fruit bat (R. aegyptiacus). The sequences were compared with those of 22 other mammals, including nine bats, available in the database. We identified that megabat genomes are distinct in that they have extremely low activity of SINE retrotranspositions, expansion of two chemosensory gene families, including the trace amine receptor (TAAR) and olfactory receptor (OR), and elevation of the dN/dS ratio in genes for immunity and protein catabolism. The adaptive signatures discovered in the genomes of megabats may provide crucial insight into their distinct evolution, including key processes such as virus resistance, loss of echolocation, and frugivorous feeding.
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Metabolism of Odorant Molecules in Human Nasal/Oral Cavity Affects the Odorant Perception. 査読あり
Ijichi C, Wakabayashi H, Sugiyama S, Ihara Y, Nogi Y, Nagashima A, Ihara S, Niimura Y, Shimizu Y, Kondo K, Touhara K
Chemical senses 44 ( 7 ) 465 - 481 2019年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
In this study, we examined the mode of metabolism of food odorant molecules in the human nasal/oral cavity in vitro and in vivo. We selected 4 odorants, 2-furfurylthiol (2-FT), hexanal, benzyl acetate, and methyl raspberry ketone, which are potentially important for designing food flavors. In vitro metabolic assays of odorants with saliva/nasal mucus analyzed by gas chromatography mass spectrometry revealed that human saliva and nasal mucus exhibit the following 3 enzymatic activities: (i) methylation of 2-FT into furfuryl methylsulfide (FMS); (ii) reduction of hexanal into hexanol; and (iii) hydrolysis of benzyl acetate into benzyl alcohol. However, (iv) demethylation of methyl raspberry ketone was not observed. Real-time in vivo analysis using proton transfer reaction-mass spectrometry demonstrated that the application of 2-FT and hexanal through 3 different pathways via the nostril or through the mouth generated the metabolites FMS and hexanol within a few seconds. The concentration of FMS and hexanol in the exhaled air was above the perception threshold. A cross-adaptation study based on the activation pattern of human odorant receptors suggested that this metabolism affects odor perception. These results suggest that some odorants in food are metabolized in the human nasal mucus/saliva, and the resulting metabolites are perceived as part of the odor quality of the substrates. Our results help improve the understanding of the mechanism of food odor perception and may enable improved design and development of foods in relation to odor.
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Acceleration of Olfactory Receptor Gene Loss in Primate Evolution: Possible Link to Anatomical Change in Sensory Systems and Dietary Transition. 査読あり
Niimura Y, Matsui A, Touhara K
Molecular biology and evolution 35 ( 6 ) 1437 - 1450 2018年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
Primates have traditionally been regarded as vision-oriented animals with low olfactory ability, though this "microsmatic primates" view has been challenged recently. To clarify when and how degeneration of the olfactory system occurred and to specify the relevant factors during primate evolution, we here examined the olfactory receptor (OR) genes from 24 phylogenetically and ecologically diverse primate species. The results revealed that strepsirrhines with curved noses had functional OR gene repertoires that were nearly twice as large as those for haplorhines with simple noses. Neither activity pattern (nocturnal/diurnal) nor color vision system showed significant correlation with the number of functional OR genes while phylogeny and nose structure (haplorhine/strepsirrhine) are statistically controlled, but extent of folivory did. We traced the evolutionary fates of individual OR genes by identifying orthologous gene groups, demonstrating that the rates of OR gene losses were accelerated at the ancestral branch of haplorhines, which coincided with the acquisition of acute vision. The highest rate of OR gene loss was observed at the ancestral branch of leaf-eating colobines; this reduction is possibly linked with the dietary transition from frugivory to folivory because odor information is essential for fruit foraging but less so for leaf foraging. Intriguingly, we found accelerations of OR gene losses in an external branch to every hominoid species examined. These findings suggest that the current OR gene repertoire in each species has been shaped by a complex interplay of phylogeny, anatomy, and habitat; therefore, multiple factors may contribute to the olfactory degeneration in primates.
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A long-range cis-regulatory element for class I odorant receptor genes. 査読あり
Iwata T, Niimura Y, Kobayashi C, Shirakawa D, Suzuki H, Enomoto T, Touhara K, Yoshihara Y, Hirota J
Nature communications 8 ( 1 ) 885 - 885 2017年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：NATURE PUBLISHING GROUP
Individual olfactory sensory neurons express a single odorant receptor gene from either class I genes residing in a single cluster on a single chromosome or class II genes spread over multiple clusters on multiple chromosomes. Here, we identify an enhancer element for mouse class I genes, the J element, that is conserved through mammalian species from the platypus to humans. The J element regulates most class I genes expression by exerting an effect over ~ 3 megabases within the whole cluster. Deletion of the trans J element increases the expression frequencies of class I genes from the intact J allele, indicating that the allelic exclusion of class I genes depends on the activity of the J element. Our data reveal a long-range cis-regulatory element that governs the singular class I gene expression and has been phylogenetically preserved to retain a single cluster organization of class I genes in mammals."Each olfactory sensory neuron expresses a single odorant receptor gene from either class I or class II genes. Here, the authors identify an enhancer for mouse class I genes, that is highly conserved, and regulates most class I genes expression by acting over ~ 3 megabases within the whole cluster."
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Comparative genomic analysis of translation initiation mechanisms for genes lacking the Shine-Dalgarno sequence in prokaryotes. 査読あり
Nakagawa S, Niimura Y, Gojobori T
Nucleic acids research 45 ( 7 ) 3922 - 3931 2017年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
In prokaryotes, translation initiation is believed to occur through an interaction between the 3΄ tail of a 16S rRNA and a corresponding Shine-Dalgarno (SD) sequence in the 5΄ untranslated region (UTR) of an mRNA. However, some genes lack SD sequences (non-SD genes), and the fraction of non-SD genes in a genome varies depending on the prokaryotic species. To elucidate non-SD translation initiation mechanisms in prokaryotes from an evolutionary perspective, we statistically examined the nucleotide frequencies around the initiation codons in non-SD genes from 260 prokaryotes (235 bacteria and 25 archaea). We identified distinct nucleotide frequency biases upstream of the initiation codon in bacteria and archaea, likely because of the presence of leaderless mRNAs lacking a 5΄ UTR. Moreover, we observed overall similarities in the nucleotide patterns between upstream and downstream regions of the initiation codon in all examined phyla. Symmetric nucleotide frequency biases might facilitate translation initiation by preventing the formation of secondary structures around the initiation codon. These features are more prominent in species' genomes that harbor large fractions of non-SD sequences, suggesting that a reduced stability around the initiation codon is important for efficient translation initiation in prokaryotes.
DOI： 10.1093/nar/gkx124
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Sato-Akuhara N, Horio N, Kato-Namba A, Yoshikawa K, Niimura Y, Ihara S, Shirasu M, Touhara K
The Journal of neuroscience : the official journal of the Society for Neuroscience 36 ( 16 ) 4482 - 91 2016年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
UNLABELLED: Musk odors have been used widely for fragrance and medicine for >2000 years because of their fascinating scent and physiological effects. Therefore, fragrance manufacturers have been eager to develop high-quality musk compounds that are safe and easily synthesized. We recently identified muscone-responsive olfactory receptors (ORs) MOR215-1 and OR5AN1 in mice and humans, respectively (Shirasu et al., 2014). In this study, we identified musk ORs that are evolutionarily closely related to MOR215-1 or OR5AN1 in various primates and investigated structure-activity relationships for various musk odorants and related compounds. We found that each species has one or two functional musk ORs that exhibit specific ligand spectra to musk compounds. Some of them, including the human OR5AN1, responded to nitro musks with chemical properties distinct from muscone. The ligand specificity of OR5AN1 reflects the perception of musk odors in humans. Genetic deletion of MOR215-1 in mice resulted in drastic reduction of sensitivity to muscone, suggesting that MOR215-1 plays a critical role in muscone perception. Therefore, the current study reveals a clear link between the identified OR and muscone perception. Moreover, the strategy established for screening ligands for the muscone OR may facilitate the development of novel and commercially useful musk odors. SIGNIFICANCE STATEMENT: The long-sought musk odor receptor family in mammals was discovered and found to be well conserved and narrowly tuned to musk odors. In mice, deletion of the most sensitive musk receptor resulted in drastic reduction in sensitivity to muscone, demonstrating a strong link between receptor and odor perception. In humans, we found one musk receptor that recognized both macrocyclic and nitro musks that had distinct chemical structures. The structure-activity relationships were in a good agreement with human sensory perception and therefore may be used to develop novel musk aroma in fragrance fields. Finally, identification of a natural ligand(s) for musk receptors in mammals other than musk deer would reveal an evolutionarily pivotal role in each species in the future.
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NIRS-based language learning BCI system 査読あり
Ko Watanabe, Hiroshi Tanaka, Kensho Takahashi, Yoshihito Niimura, Kajiro Watanabe, Yosuke Kurihara
IEEE Sensors Journal 16 ( 8 ) 2726 - 2734 2016年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Institute of Electrical and Electronics Engineers Inc.
This paper describes a non-invasive, less restrictive, stable measurement system for a brain-computer interface (BCI) for second-language (L2) learning. The system outputs the arousal of the Yerkes-Dodson law. We employ non-invasive nearinfrared spectroscopy (NIRS) as a basic device to measure the blood volume. However, the blood volume measured by NIRS includes base-line drift and is not stable. Here, we introduce a new drift-free variable defined as blood flow, which is the time derivative of the blood volume. Problems to be considered are: 1) Can the blood flow represent brain activity? 2) Where are the fewest brain areas strongly influenced by the language listening? 3) What parameter expresses arousal? We also present a measurement system. To verify the system, we carried out experiments with 40 listeners (10 advanced, 15 intermediate, and 15 novice listeners). When advanced L2 listeners were listening to the first and second languages, the distribution patterns of the root mean squares of the blood flow in the prefrontal regions were close to the correlation coefficient of 0.89, which shows that blood flow can represent brain activity in language processing. The center of BA10 and the right and left BA46 in the prefrontal regions were sufficient to detect language processing. The root mean squares of the differences of the left and right BA46 from BA10 peaked at a certain L2 readability level for all L2 listeners
they can be the parameter that expresses arousal. Thus, the measurement system can function as an input measurement device for BCI. -
Vertebrate Odorant Receptors 査読あり
Kazushige Touhara, Yoshihito Niimura, Sayoko Ihara
Chemosensory Transduction: The Detection of Odors, Tastes, and Other Chemostimuli 49 - 66 2016年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Elsevier Inc.
How we can sense and distinguish thousands of odorants in the external world has been a great mystery. The discovery of the olfactory receptor (OR) gene family in 1991 has elucidated some of the mechanisms underlying the remarkable discriminatory power of the vertebrate olfactory system. The OR family comprises a few hundred to 2000 genes whose products recognize a larger set of odorant molecules that vary in size and shape. Until now, a multiple odorants-multiple receptors combination theory has accounted for the discriminatory mechanism. Here we review the history of the discovery of the OR genes, the evolution of the OR gene family, and the structure and function of ORs in primates and other vertebrate species.
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Temporal changes in NIRS outputs in prefrontal regions when listening to languages 査読あり
Ko Watanabe, Yoshihito Niimura, Yosuke Kurihara, Kajiro Watanabe
Artificial Life and Robotics 20 ( 2 ) 183 - 189 2015年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Springer-Verlag Tokyo
As a non-invasive brain activity measurement method, near-infrared spectroscopy (NIRS) technology has been used widely, but it has the problem of noise corruption by baseline drifting. In this paper, we employ a time derivative of NIRS output which is the blood flow with high-pass filtering characteristics. We investigate whether blood flow can reasonably localize and represent brain activity or not when listening to languages. The blood flow distribution pattern by advanced second language (L2) listeners when listening to L2 was determined to be the most similar to that when listening to their first language (L1). This study shows this form of analysis has proved to be more accurate than conventional parameters. In experiments with 40 healthy subjects, the blood flow was localized to the left BA46 of advanced L2 listeners and to the right BA46 of intermediate L2 listeners. Hence, the blood flow is insensitive to the baseline drift noise and stably localizes brain activity areas.
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Corrigendum: Extreme expansion of the olfactory receptor gene repertoire in African elephants and evolutionary dynamics of orthologous gene groups in 13 placental mammals. 査読あり
Niimura Y, Matsui A, Touhara K
Genome research 25 ( 6 ) 926 2015年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Extreme expansion of the olfactory receptor gene repertoire in African elephants and evolutionary dynamics of orthologous gene groups in 13 placental mammals. 査読あり
Niimura Y, Matsui A, Touhara K
Genome research 24 ( 9 ) 1485 - 96 2014年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
Olfactory receptors (ORs) detect odors in the environment, and OR genes constitute the largest multigene family in mammals. Numbers of OR genes vary greatly among species--reflecting the respective species' lifestyles--and this variation is caused by frequent gene gains and losses during evolution. However, whether the extent of gene gains/losses varies among individual gene lineages and what might generate such variation is unknown. To answer these questions, we used a newly developed phylogeny-based method to classify >10,000 intact OR genes from 13 placental mammal species into 781 orthologous gene groups (OGGs); we then compared the OGGs. Interestingly, African elephants had a surprisingly large repertoire (∼ 2000) of functional OR genes encoded in enlarged gene clusters. Additionally, OR gene lineages that experienced more gene duplication had weaker purifying selection, and Class II OR genes have evolved more dynamically than those in Class I. Some OGGs were highly expanded in a lineage-specific manner, while only three OGGs showed complete one-to-one orthology among the 13 species without any gene gains/losses. These three OGGs also exhibited highly conserved amino acid sequences; therefore, ORs in these OGGs may have physiologically important functions common to every placental mammal. This study provides a basis for inferring OR functions from evolutionary trajectory.
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The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan. 査読あり
Wang Z, Pascual-Anaya J, Zadissa A, Li W, Niimura Y, Huang Z, Li C, White S, Xiong Z, Fang D, Wang B, Ming Y, Chen Y, Zheng Y, Kuraku S, Pignatelli M, Herrero J, Beal K, Nozawa M, Li Q, Wang J, Zhang H, Yu L, Shigenobu S, Wang J, Liu J, Flicek P, Searle S, Wang J, Kuratani S, Yin Y, Aken B, Zhang G, Irie N
Nature genetics 45 ( 6 ) 701 - 706 2013年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：6
The unique anatomical features of turtles have raised unanswered questions about the origin of their unique body plan. We generated and analyzed draft genomes of the soft-shell turtle (Pelodiscus sinensis) and the green sea turtle (Chelonia mydas); our results indicated the close relationship of the turtles to the bird-crocodilian lineage, from which they split ∼267.9-248.3 million years ago (Upper Permian to Triassic). We also found extensive expansion of olfactory receptor genes in these turtles. Embryonic gene expression analysis identified an hourglass-like divergence of turtle and chicken embryogenesis, with maximal conservation around the vertebrate phylotypic period, rather than at later stages that show the amniote-common pattern. Wnt5a expression was found in the growth zone of the dorsal shell, supporting the possible co-option of limb-associated Wnt signaling in the acquisition of this turtle-specific novelty. Our results suggest that turtle evolution was accompanied by an unexpectedly conservative vertebrate phylotypic period, followed by turtle-specific repatterning of development to yield the novel structure of the shell.
DOI： 10.1038/ng.2615
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A methodical microarray design enables surveying of expression of a broader range of genes in Ciona intestinalis. 査読あり
Matsumae H, Hamada M, Fujie M, Niimura Y, Tanaka H, Kawashima T
Gene 519 ( 1 ) 82 - 90 2013年4月
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Identification of chemosensory receptor genes from vertebrate genomes. 査読あり
Niimura Y
Methods in molecular biology (Clifton, N.J.) 1068 95 - 105 2013年
記述言語：英語 掲載種別：研究論文（学術雑誌）
Chemical senses are essential for the survival of animals. In vertebrates, mainly three different types of receptors, olfactory receptors (ORs), vomeronasal receptors type 1 (V1Rs), and vomeronasal receptors type 2 (V2Rs), are responsible for the detection of chemicals in the environment. Mouse or rat genomes contain >1,000 OR genes, forming the largest multigene family in vertebrates, and have >100 V1R and V2R genes as well. Recent advancement in genome sequencing enabled us to computationally identify nearly complete repertories of OR, V1R, and V2R genes from various organisms, revealing that the numbers of these genes are highly variable among different organisms depending on each species' living environment. Here I would explain bioinformatic methods to identify the entire repertoires of OR, V1R, and V2R genes from vertebrate genome sequences.
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Identification of olfactory receptor genes from mammalian genome sequences. 査読あり
Niimura Y
Methods in molecular biology (Clifton, N.J.) 1003 39 - 49 2013年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Humana Press Inc.
Olfaction is essential for the survival of mammals. Diverse odorant molecules in the environment are detected by olfactory receptors (ORs) expressed in the olfactory epithelium of the nasal cavity. In general, mammalian genomes harbor ~1,000 OR genes, which form the largest multigene family in mammals. The recent advances in genome sequencing technology have enabled us to computationally identify nearly complete repertoires of OR genes from various organisms. Such studies have revealed that the numbers of OR genes are highly variable among organisms depending on their living environments. Because OR genes are intronless, it is possible to find all OR genes by conducting homology searches against the genome sequences using known OR genes as queries. However, some caution is necessary during the process of extracting intact coding sequences of OR genes and distinguishing among OR and non-OR genes. Presented here is a description of bioinformatics methods to identify the entire OR gene repertoires from mammalian genome sequences.
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Olfactory receptor multigene family in vertebrates: from the viewpoint of evolutionary genomics. 査読あり
Niimura Y
Current genomics 13 ( 2 ) 103 - 14 2012年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BENTHAM SCIENCE PUBL LTD
Olfaction is essential for the survival of animals. Diverse odor molecules in the environment are detected by the olfactory receptors (ORs) in the olfactory epithelium of the nasal cavity. There are ~400 and ~1,000 OR genes in the human and mouse genomes, respectively, forming the largest multigene family in mammals. The relationships between ORs and odorants are multiple-to-multiple, which allows for discriminating almost unlimited number of different odorants by a combination of ORs. However, the OR-ligand relationships are still largely unknown, and predicting the quality of odor from its molecular structure is unsuccessful.Extensive bioinformatic analyses using the whole genomes of various organisms revealed a great variation in number of OR genes among species, reflecting the diversity of their living environments. For example, higher primates equipped with a well-developed vision system and dolphins that are secondarily adapted to the aquatic life have considerably smaller numbers of OR genes than most of other mammals do. OR genes are characterized by extremely frequent gene duplications and losses. The OR gene repertories are also diverse among human individuals, explaining the diversity of odor perception such as the specific anosmia.OR genes are present in all vertebrates. The number of OR genes is smaller in teleost fishes than in mammals, while the diversity is higher in the former than the latter. Because the genome of amphioxus, the most basal chordate species, harbors vertebrate-like OR genes, the origin of OR genes can be traced back to the common ancestor of the phylum Chordata.
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hzAnalyzer: detection, quantification, and visualization of contiguous homozygosity in high-density genotyping datasets. 査読あり
Johnson TA, Niimura Y, Tanaka H, Nakamura Y, Tsunoda T
Genome biology 12 ( 3 ) R21 2011年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：3
The analysis of contiguous homozygosity (runs of homozygous loci) in human genotyping datasets is critical in the search for causal disease variants in monogenic disorders, studies of population history and the identification of targets of natural selection. Here, we report methods for extracting homozygous segments from high-density genotyping datasets, quantifying their local genomic structure, identifying outstanding regions within the genome and visualizing results for comparative analysis between population samples.
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Difference in gene duplicability may explain the difference in overall structure of protein-protein interaction networks among eukaryotes. 査読あり
Hase T, Niimura Y, Tanaka H
BMC evolutionary biology 10 358 - 358 2010年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BIOMED CENTRAL LTD
BACKGROUND: A protein-protein interaction network (PIN) was suggested to be a disassortative network, in which interactions between high- and low-degree nodes are favored while hub-hub interactions are suppressed. It was postulated that a disassortative structure minimizes unfavorable cross-talks between different hub-centric functional modules and was positively selected in evolution. However, by re-examining yeast PIN data, several researchers reported that the disassortative structure observed in a PIN might be an experimental artifact. Therefore, the existence of a disassortative structure and its possible evolutionary mechanism remains unclear. RESULTS: In this study, we investigated PINs from the yeast, worm, fly, human, and malaria parasite including four different yeast PIN datasets. The analyses showed that the yeast, worm, fly, and human PINs are disassortative while the malaria parasite PIN is not. By conducting simulation studies on the basis of a duplication-divergence model, we demonstrated that a preferential duplication of low- and high-degree nodes can generate disassortative and non-disassortative networks, respectively. From this observation, we hypothesized that the difference in degree dependence on gene duplications accounts for the difference in assortativity of PINs among species. Comparison of 55 proteomes in eukaryotes revealed that genes with lower degrees showed higher gene duplicabilities in the yeast, worm, and fly, while high-degree genes tend to have high duplicabilities in the malaria parasite, supporting the above hypothesis. CONCLUSIONS: These results suggest that disassortative structures observed in PINs are merely a byproduct of preferential duplications of low-degree genes, which might be caused by an organism's living environment.
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Degeneration of olfactory receptor gene repertories in primates: no direct link to full trichromatic vision. 査読あり
Matsui A, Go Y, Niimura Y
Molecular biology and evolution 27 ( 5 ) 1192 - 200 2010年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：OXFORD UNIV PRESS
Odor molecules in the environment are detected by olfactory receptors (ORs), being encoded by a large multigene family in mammalian genomes. It is generally thought that primates are vision oriented and dependent weakly on olfaction. Previous studies suggested that Old World monkeys (OWMs) and hominoids lost many functional OR genes after the divergence from New World monkeys (NWMs) due to the acquisition of well-developed trichromatic vision. To examine this hypothesis, here we analyzed OR gene repertoires of five primate species including NWMs, OWMs, and hominoids for which high-coverage genome sequences are available, together with two prosimians and tree shrews with low-coverage genomes. The results showed no significant differences in the number of functional OR genes between NWMs (marmosets) and OWMs/hominoids. Two independent analyses, identification of orthologous genes among the five primates and estimation of the numbers of ancestral genes by the reconciled tree method, did not support a sudden loss of OR genes at the branch of the OWMs/hominoids ancestor but suggested a gradual loss in every lineage. Moreover, we found that humans retain larger numbers of ancestral OR genes that were in the common ancestor of NWMs/OWMs/hominoids than orangutans and macaques and that the OR gene repertoire in humans is more similar to that of marmosets than those of orangutans and macaques. These results suggest that the degeneration of OR genes in primates cannot simply be explained by the acquisition of trichromatic vision, and our sense of smell may not be inferior to other primate species.
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Dynamic evolution of translation initiation mechanisms in prokaryotes. 査読あり
Nakagawa S, Niimura Y, Miura K, Gojobori T
Proceedings of the National Academy of Sciences of the United States of America 107 ( 14 ) 6382 - 7 2010年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：NATL ACAD SCIENCES
It is generally believed that prokaryotic translation is initiated by the interaction between the Shine-Dalgarno (SD) sequence in the 5' UTR of an mRNA and the anti-SD sequence in the 3' end of a 16S ribosomal RNA. However, there are two exceptional mechanisms, which do not require the SD sequence for translation initiation: one is mediated by a ribosomal protein S1 (RPS1) and the other used leaderless mRNA that lacks its 5' UTR. To understand the evolutionary changes of the mechanisms of translation initiation, we examined how universal the SD sequence is as an effective initiator for translation among prokaryotes. We identified the SD sequence from 277 species (249 eubacteria and 28 archaebacteria). We also devised an SD index that is a proportion of SD-containing genes in which the differences of GC contents are taken into account. We found that the SD indices varied among prokaryotic species, but were similar within each phylum. Although the anti-SD sequence is conserved among species, loss of the SD sequence seems to have occurred multiple times, independently, in different phyla. For those phyla, RPS1-mediated or leaderless mRNA-used mechanisms of translation initiation are considered to be working to a greater extent. Moreover, we also found that some species, such as Cyanobacteria, may acquire new mechanisms of translation initiation. Our findings indicate that, although translation initiation is indispensable for all protein-coding genes in the genome of every species, its mechanisms have dynamically changed during evolution.
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Evolutionary dynamics of olfactory receptor genes in chordates: interaction between environments and genomic contents. 査読あり
Niimura Y
Human genomics 4 ( 2 ) 107 - 18 2009年12月
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On the origin and evolution of vertebrate olfactory receptor genes: comparative genome analysis among 23 chordate species. 査読あり
Niimura Y
Genome biology and evolution 1 34 - 44 2009年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：OXFORD UNIV PRESS
Olfaction is a primitive sense in organisms. Both vertebrates and insects have receptors for detecting odor molecules in the environment, but the evolutionary origins of these genes are different. Among studied vertebrates, mammals have approximately 1,000 olfactory receptor (OR) genes, whereas teleost fishes have much smaller (approximately 100) numbers of OR genes. To investigate the origin and evolution of vertebrate OR genes, I attempted to determine near-complete OR gene repertoires by searching whole-genome sequences of 14 nonmammalian chordates, including cephalochordates (amphioxus), urochordates (ascidian and larvacean), and vertebrates (sea lamprey, elephant shark, five teleost fishes, frog, lizard, and chicken), followed by a large-scale phylogenetic analysis in conjunction with mammalian OR genes identified from nine species. This analysis showed that the amphioxus has >30 vertebrate-type OR genes though it lacks distinctive olfactory organs, whereas all OR genes appear to have been lost in the urochordate lineage. Some groups of genes (theta, kappa, and lambda) that are phylogenetically nested within vertebrate OR genes showed few gene gains and losses, which is in sharp contrast to the evolutionary pattern of OR genes, suggesting that they are actually non-OR genes. Moreover, the analysis demonstrated a great difference in OR gene repertoires between aquatic and terrestrial vertebrates, reflecting the necessity for the detection of water-soluble and airborne odorants, respectively. However, a minor group (beta) of genes that are atypically present in both aquatic and terrestrial vertebrates was also found. These findings should provide a critical foundation for further physiological, behavioral, and evolutionary studies of olfaction in various organisms.
DOI： 10.1093/gbe/evp003
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The evolution of animal chemosensory receptor gene repertoires: roles of chance and necessity. 査読あり
Nei M, Niimura Y, Nozawa M
Nature reviews. Genetics 9 ( 12 ) 951 - 63 2008年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：NATURE PUBLISHING GROUP
Chemosensory receptors are essential for the survival of organisms that range from bacteria to mammals. Recent studies have shown that the numbers of functional chemosensory receptor genes and pseudogenes vary enormously among the genomes of different animal species. Although much of the variation can be explained by the adaptation of organisms to different environments, it has become clear that a substantial portion is generated by genomic drift, a random process of gene duplication and deletion. Genomic drift also generates a substantial amount of copy-number variation in chemosensory receptor genes within species. It seems that mutation by gene duplication and inactivation has important roles in both the adaptive and non-adaptive evolution of chemosensation.
DOI： 10.1038/nrg2480
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Similar numbers but different repertoires of olfactory receptor genes in humans and chimpanzees. 査読あり
Go Y, Niimura Y
Molecular biology and evolution 25 ( 9 ) 1897 - 907 2008年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：OXFORD UNIV PRESS
Animals recognize their external world through the detection of tens of thousands of chemical odorants. Olfactory receptor (OR) genes encode proteins for detecting odorant molecules and form the largest multigene family in mammals. It is known that humans have fewer OR genes and a higher fraction of OR pseudogenes than mice or dogs. To investigate whether these features are human specific or common to all higher primates, we identified nearly complete sets of OR genes from the chimpanzee and macaque genomes and compared them with the human OR genes. In contrast to previous studies, here we show that the number of OR genes ( approximately 810) and the fraction of pseudogenes (51%) in chimpanzees are very similar to those in humans, though macaques have considerably fewer OR genes. The pseudogenization rates and the numbers of genes affected by positive selection are also similar between humans and chimpanzees. Moreover, the most recent common ancestor between humans and chimpanzees had a larger number of functional OR genes (>500) and a lower fraction of pseudogenes (41%) than its descendents, suggesting that the OR gene repertoires are in a phase of deterioration in both lineages. Interestingly, despite the close evolutionary relationship between the 2 species, approximately 25% of their functional gene repertoires are species specific due to massive gene losses. These findings suggest that the tempo of evolution of OR genes is similar between humans and chimpanzees, but the OR gene repertoires are quite different between them. This difference might be responsible for the species-specific ability of odor perception.
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Non-uniform survival rate of heterodimerization links in the evolution of the yeast protein-protein interaction network. 査読あり
Hase T, Niimura Y, Kaminuma T, Tanaka H
PloS one 3 ( 2 ) e1667 2008年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：PUBLIC LIBRARY SCIENCE
Protein-protein interaction networks (PINs) are scale-free networks with a small-world property. In a small-world network, the average cluster coefficient (<C>) is much higher than in a random network, but the average shortest path length (<L>) is similar between the two networks. To understand the evolutionary mechanisms shaping the structure of PINs, simulation studies using various network growth models have been performed. It has been reported that the heterodimerization (HD) model, in which a new link is added between duplicated nodes with a uniform probability, could reproduce scale-freeness and a high <C>. In this paper, however, we show that the HD model is unsatisfactory, because (i) to reproduce the high <C> in the yeast PIN, a much larger number (n(HI)) of HD links (links between duplicated nodes) are required than the estimated number of n(HI) in the yeast PIN and (ii) the spatial distribution of triangles in the yeast PIN is highly skewed but the HD model cannot reproduce the skewed distribution. To resolve these discrepancies, we here propose a new model named the non-uniform heterodimerization (NHD) model. In this model, an HD link is preferentially attached between duplicated nodes when they share many common neighbors. Simulation studies demonstrated that the NHD model can successfully reproduce the high <C>, the low n(HI), and the skewed distribution of triangles in the yeast PIN. These results suggest that the survival rate of HD links is not uniform in the evolution of PINs, and that an HD link between high-degree nodes tends to be evolutionarily conservative. The non-uniform survival rate of HD links can be explained by assuming a low mutation rate for a high-degree node, and thus this model appears to be biologically plausible.
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Diversity of preferred nucleotide sequences around the translation initiation codon in eukaryote genomes. 査読あり
Nakagawa S, Niimura Y, Gojobori T, Tanaka H, Miura K
Nucleic acids research 36 ( 3 ) 861 - 71 2008年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：OXFORD UNIV PRESS
Understanding regulatory mechanisms of protein synthesis in eukaryotes is essential for the accurate annotation of genome sequences. Kozak reported that the nucleotide sequence GCCGCC(A/G)CCAUGG (AUG is the initiation codon) was frequently observed in vertebrate genes and that this 'consensus' sequence enhanced translation initiation. However, later studies using invertebrate, fungal and plant genes reported different 'consensus' sequences. In this study, we conducted extensive comparative analyses of nucleotide sequences around the initiation codon by using genomic data from 47 eukaryote species including animals, fungi, plants and protists. The analyses revealed that preferred nucleotide sequences are quite diverse among different species, but differences between patterns of nucleotide bias roughly reflect the evolutionary relationships of the species. We also found strong biases of A/G at position -3, A/C at position -2 and C at position +5 that were commonly observed in all species examined. Genes with higher expression levels showed stronger signals, suggesting that these nucleotides are responsible for the regulation of translation initiation. The diversity of preferred nucleotide sequences around the initiation codon might be explained by differences in relative contributions from two distinct patterns, GCCGCCAUG and AAAAAAAUG, which implies the presence of multiple molecular mechanisms for controlling translation initiation.
DOI： 10.1093/nar/gkm1102
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The H-Invitational Database (H-InvDB), a comprehensive annotation resource for human genes and transcripts. 査読あり
Genome Information Integration Project And H-Invitational 2., Yamasaki C, Murakami K, Fujii Y, Sato Y, Harada E, Takeda J, Taniya T, Sakate R, Kikugawa S, Shimada M, Tanino M, Koyanagi KO, Barrero RA, Gough C, Chun HW, Habara T, Hanaoka H, Hayakawa Y, Hilton PB, Kaneko Y, Kanno M, Kawahara Y, Kawamura T, Matsuya A, Nagata N, Nishikata K, Noda AO, Nurimoto S, Saichi N, Sakai H, Sanbonmatsu R, Shiba R, Suzuki M, Takabayashi K, Takahashi A, Tamura T, Tanaka M, Tanaka S, Todokoro F, Yamaguchi K, Yamamoto N, Okido T, Mashima J, Hashizume A, Jin L, Lee KB, Lin YC, Nozaki A, Sakai K, Tada M, Miyazaki S, Makino T, Ohyanagi H, Osato N, Tanaka N, Suzuki Y, Ikeo K, Saitou N, Sugawara H, O'Donovan C, Kulikova T, Whitfield E, Halligan B, Shimoyama M, Twigger S, Yura K, Kimura K, Yasuda T, Nishikawa T, Akiyama Y, Motono C, Mukai Y, Nagasaki H, Suwa M, Horton P, Kikuno R, Ohara O, Lancet D, Eveno E, Graudens E, Imbeaud S, Debily MA, Hayashizaki Y, Amid C, Han M, Osanger A, Endo T, Thomas MA, Hirakawa M, Makalowski W, Nakao M, Kim NS, Yoo HS, De Souza SJ, Bonaldo Mde F, Niimura Y, Kuryshev V, Schupp I, Wiemann S, Bellgard M, Shionyu M, Jia L, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Zhang Q, Go M, Minoshima S, Ohtsubo M, Hanada K, Tonellato P, Isogai T, Zhang J, Lenhard B, Kim S, Chen Z, Hinz U, Estreicher A, Nakai K, Makalowska I, Hide W, Tiffin N, Wilming L, Chakraborty R, Soares MB, Chiusano ML, Suzuki Y, Auffray C, Yamaguchi-Kabata Y, Itoh T, Hishiki T, Fukuchi S, Nishikawa K, Sugano S, Nomura N, Tateno Y, Imanishi T, Gojobori T
Nucleic acids research 36 ( Database issue ) D793 - 9 2008年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：OXFORD UNIV PRESS
Here we report the new features and improvements in our latest release of the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/), a comprehensive annotation resource for human genes and transcripts. H-InvDB, originally developed as an integrated database of the human transcriptome based on extensive annotation of large sets of full-length cDNA (FLcDNA) clones, now provides annotation for 120 558 human mRNAs extracted from the International Nucleotide Sequence Databases (INSD), in addition to 54 978 human FLcDNAs, in the latest release H-InvDB_4.6. We mapped those human transcripts onto the human genome sequences (NCBI build 36.1) and determined 34 699 human gene clusters, which could define 34 057 (98.1%) protein-coding and 642 (1.9%) non-protein-coding loci; 858 (2.5%) transcribed loci overlapped with predicted pseudogenes. For all these transcripts and genes, we provide comprehensive annotation including gene structures, gene functions, alternative splicing variants, functional non-protein-coding RNAs, functional domains, predicted sub cellular localizations, metabolic pathways, predictions of protein 3D structure, mapping of SNPs and microsatellite repeat motifs, co-localization with orphan diseases, gene expression profiles, orthologous genes, protein-protein interactions (PPI) and annotation for gene families. The current H-InvDB annotation resources consist of two main views: Transcript view and Locus view and eight sub-databases: the DiseaseInfo Viewer, H-ANGEL, the Clustering Viewer, G-integra, the TOPO Viewer, Evola, the PPI view and the Gene family/group.
DOI： 10.1093/nar/gkm999
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Extensive gains and losses of olfactory receptor genes in mammalian evolution. 査読あり
Niimura Y, Nei M
PloS one 2 ( 8 ) e708 2007年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：PUBLIC LIBRARY SCIENCE
Odor perception in mammals is mediated by a large multigene family of olfactory receptor (OR) genes. The number of OR genes varies extensively among different species of mammals, and most species have a substantial number of pseudogenes. To gain some insight into the evolutionary dynamics of mammalian OR genes, we identified the entire set of OR genes in platypuses, opossums, cows, dogs, rats, and macaques and studied the evolutionary change of the genes together with those of humans and mice. We found that platypuses and primates have <400 functional OR genes while the other species have 800-1,200 functional OR genes. We then estimated the numbers of gains and losses of OR genes for each branch of the phylogenetic tree of mammals. This analysis showed that (i) gene expansion occurred in the placental lineage each time after it diverged from monotremes and from marsupials and (ii) hundreds of gains and losses of OR genes have occurred in an order-specific manner, making the gene repertoires highly variable among different orders. It appears that the number of OR genes is determined primarily by the functional requirement for each species, but once the number reaches the required level, it fluctuates by random duplication and deletion of genes. This fluctuation seems to have been aided by the stochastic nature of OR gene expression.
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Evolutionary dynamics of olfactory and other chemosensory receptor genes in vertebrates. 査読あり
Niimura Y, Nei M
Journal of human genetics 51 ( 6 ) 505 - 517 2006年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：SPRINGER TOKYO
The numbers of functional olfactory receptor (OR) genes in humans and mice are about 400 and 1,000 respectively. In both humans and mice, these genes exist as genomic clusters and are scattered over almost all chromosomes. The difference in the number of genes between the two species is apparently caused by massive inactivation of OR genes in the human lineage and a substantial increase of OR genes in the mouse lineage after the human-mouse divergence. Compared with mammals, fishes have a much smaller number of OR genes. However, the OR gene family in fishes is much more divergent than that in mammals. Fishes have many different groups of genes that are absent in mammals, suggesting that the mammalian OR gene family is characterized by the loss of many group genes that existed in the ancestor of vertebrates and the subsequent expansion of specific groups of genes. Therefore, this gene family apparently changed dynamically depending on the evolutionary lineage and evolved under the birth-and-death model of evolution. Study of the evolutionary changes of two gene families for vomeronasal receptors and two gene families for taste receptors, which are structurally similar, but remotely related to OR genes, showed that some of the gene families evolved in the same fashion as the OR gene family. It appears that the number and types of genes in chemosensory receptor gene families have evolved in response to environmental needs, but they are also affected by fortuitous factors.
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Evolutionary dynamics of olfactory receptor genes in fishes and tetrapods. 査読あり
Niimura Y, Nei M
Proceedings of the National Academy of Sciences of the United States of America 102 ( 17 ) 6039 - 44 2005年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：NATL ACAD SCIENCES
Olfaction, which is an important physiological function for the survival of mammals, is controlled by a large multigene family of olfactory receptor (OR) genes. Fishes also have this gene family, but the number of genes is known to be substantially smaller than in mammals. To understand the evolutionary dynamics of OR genes, we conducted a phylogenetic analysis of all functional genes identified from the genome sequences of zebrafish, pufferfish, frogs, chickens, humans, and mice. The results suggested that the most recent common ancestor between fishes and tetrapods had at least nine ancestral OR genes, and all OR genes identified were classified into nine groups, each of which originated from one ancestral gene. Eight of the nine group genes are still observed in current fish species, whereas only two group genes were found from mammalian genomes, showing that the OR gene family in fishes is much more diverse than in mammals. In mammals, however, one group of genes, gamma, expanded enormously, containing approximately 90% of the entire gene family. Interestingly, the gene groups observed in mammals or birds are nearly absent in fishes. The OR gene repertoire in frogs is as diverse as that in fishes, but the expansion of group gamma genes also occurred, indicating that the frog OR gene family has both mammal- and fish-like characters. All of these observations can be explained by the environmental change that organisms have experienced from the time of the common ancestor of all vertebrates to the present.
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Comparative evolutionary analysis of olfactory receptor gene clusters between humans and mice. 査読あり
Niimura Y, Nei M
Gene 346 13 - 21 2005年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：ELSEVIER SCIENCE BV
Olfactory receptor (OR) genes form the largest multigene family in mammalian genomes. Humans have approximately 800 OR genes, but >50% of them are pseudogenes. By contrast, mice have approximately 1400 OR genes and pseudogenes are approximately 25%. To understand the evolutionary processes that shaped the difference of OR gene families between humans and mice, we studied the genomic locations of all human and mouse OR genes and conducted a detailed phylogenetic analysis using functional genes and pseudogenes. We identified 40 phylogenetic clades with high bootstrap supports, most of which contain both human and mouse genes. Interestingly, a particular clade contains approximately 100 pseudogenes in humans, whereas the numbers of pseudogenes are <20 for most of the mouse clades. We also found that the organization of OR genomic clusters is well conserved between humans and mice in many chromosomal locations. Despite the difference in the numbers of genes, the numbers of large genomic clusters are nearly the same for humans and mice. These observations suggest that the greater OR gene repertoire in mice has been generated mainly by tandem gene duplication within each genomic cluster.
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Evolutionary changes of the number of olfactory receptor genes in the human and mouse lineages. 査読あり
Niimura Y, Nei M
Gene 346 23 - 8 2005年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：ELSEVIER SCIENCE BV
The numbers of functional olfactory receptor (OR) genes are quite variable among mammalian species. Previously we have reported that humans have 388 functional OR genes and 414 pseudogenes, while mice have 1037 functional genes and 354 pseudogenes. These observations suggest either that humans lost many functional OR genes after the human-mouse divergence (HMD) or that mice gained many functional genes. To distinguish between these two hypotheses, we devised a new method of inferring the number of functional OR genes in the most recent common ancestor (MRCA) of humans and mice. An application of this method suggested that the MRCA had approximately 750 functional OR genes and that mice acquired approximately 350 new OR genes after the HMD whereas approximately 430 OR genes in the MRCA have become pseudogenes or eliminated in the human lineage. Therefore, the two evolutionary hypotheses mentioned above are not mutually exclusive and both are nearly equally responsible for the difference in the number of OR genes between humans and mice.
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The map-based sequence of the rice genome 査読あり
International Rice, Genome Sequencing Project, Iwama, H, Gojobori, T, Itoh, T, Niimura, Y
Nature 436 793 - 800 2005年
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Evolution of olfactory receptor genes in the human genome. 査読あり
Niimura Y, Nei M
Proceedings of the National Academy of Sciences of the United States of America 100 ( 21 ) 12235 - 40 2003年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：NATL ACAD SCIENCES
Olfactory receptor (OR) genes form the largest known multigene family in the human genome. To obtain some insight into their evolutionary history, we have identified the complete set of OR genes and their chromosomal locations from the latest human genome sequences. We detected 388 potentially functional genes that have intact ORFs and 414 apparent pseudogenes. The number and the fraction (48%) of functional genes are considerably larger than the ones previously reported. The human OR genes can clearly be divided into class I and class II genes, as was previously noted. Our phylogenetic analysis has shown that the class II OR genes can further be classified into 19 phylogenetic clades supported by high bootstrap values. We have also found that there are many tandem arrays of OR genes that are phylogenetically closely related. These genes appear to have been generated by tandem gene duplication. However, the relationships between genomic clusters and phylogenetic clades are very complicated. There are a substantial number of cases in which the genes in the same phylogenetic clade are located on different chromosomal regions. In addition, OR genes belonging to distantly related phylogenetic clades are sometimes located very closely in a chromosomal region and form a tight genomic cluster. These observations can be explained by the assumption that several chromosomal rearrangements have occurred at the regions of OR gene clusters and the OR genes contained in different genomic clusters are shuffled.
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Comparative analysis of the base biases at the gene terminal portions in seven eukaryote genomes. 査読あり
Niimura Y, Terabe M, Gojobori T, Miura K
Nucleic acids research 31 ( 17 ) 5195 - 201 2003年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：OXFORD UNIV PRESS
Adenine nucleotides have been found to appear preferentially in the regions after the initiation codons or before the termination codons of bacterial genes. Our previous experiments showed that AAA and AAT, the two most frequent second codons in Escherichia coli, significantly enhance translation efficiency. To determine whether such a characteristic feature of base frequencies exists in eukaryote genes, we performed a comparative analysis of the base biases at the gene terminal portions using the proteomes of seven eukaryotes. Here we show that the base appearance at the codon third positions of gene terminal regions is highly biased in eukaryote genomes, although the codon third positions are almost free from amino acid preference. The bias changes depending on its position in a gene, and is characteristic of each species. We also found that bias is most outstanding at the second codon, the codon after the initiation codon. NCN is preferred in every genome; in particular, GCG is strongly favored in human and plant genes. The presence of the bias implies that the base sequences at the second codon affect translation efficiency in eukaryotes as well as bacteria.
DOI： 10.1093/nar/gkg701
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The genome sequence and structure of rice chromosome 1. 査読あり
Sasaki T, Matsumoto T, Yamamoto K, Sakata K, Baba T, Katayose Y, Wu J, Niimura Y, Cheng Z, Nagamura Y, Antonio BA, Kanamori H, Hosokawa S, Masukawa M, Arikawa K, Chiden Y, Hayashi M, Okamoto M, Ando T, Aoki H, Arita K, Hamada M, Harada C, Hijishita S, Honda M, Ichikawa Y, Idonuma A, Iijima M, Ikeda M, Ikeno M, Ito S, Ito T, Ito Y, Ito Y, Iwabuchi A, Kamiya K, Karasawa W, Katagiri S, Kikuta A, Kobayashi N, Kono I, Machita K, Maehara T, Mizuno H, Mizubayashi T, Mukai Y, Nagasaki H, Nakashima M, Nakama Y, Nakamichi Y, Nakamura M, Namiki N, Negishi M, Ohta I, Ono N, Saji S, Sakai K, Shibata M, Shimokawa T, Shomura A, Song J, Takazaki Y, Terasawa K, Tsuji K, Waki K, Yamagata H, Yamane H, Yoshiki S, Yoshihara R, Yukawa K, Zhong H, Iwama H, Endo T, Ito H, Hahn JH, Kim HI, Eun MY, Yano M, Jiang J, Gojobori T
Nature 420 ( 6913 ) 312 - 6 2002年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：NATURE PUBLISHING GROUP
The rice species Oryza sativa is considered to be a model plant because of its small genome size, extensive genetic map, relative ease of transformation and synteny with other cereal crops. Here we report the essentially complete sequence of chromosome 1, the longest chromosome in the rice genome. We summarize characteristics of the chromosome structure and the biological insight gained from the sequence. The analysis of 43.3 megabases (Mb) of non-overlapping sequence reveals 6,756 protein coding genes, of which 3,161 show homology to proteins of Arabidopsis thaliana, another model plant. About 30% (2,073) of the genes have been functionally categorized. Rice chromosome 1 is (G + C)-rich, especially in its coding regions, and is characterized by several gene families that are dispersed or arranged in tandem repeats. Comparison with a draft sequence indicates the importance of a high-quality finished sequence.
DOI： 10.1038/nature01184
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In silico chromosome staining: reconstruction of Giemsa bands from the whole human genome sequence. 査読あり
Niimura Y, Gojobori T
Proceedings of the National Academy of Sciences of the United States of America 99 ( 2 ) 797 - 802 2002年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：NATL ACAD SCIENCES
Giemsa staining has been used for identifying individual human chromosomes. Giemsa-dark and -light bands generally are thought to correspond to GC-poor and GC-rich regions; however, several experiments showed that the correspondence is quite poor. To elucidate the precise relationship between GC content and Giemsa banding patterns, we developed an "in silico chromosome staining" method for reconstructing Giemsa bands computationally from the whole human genome sequence. Here we show that 850-level Giemsa bands are best correlated with the difference in GC content between a local window of 2.5 megabases and a regional window of 9.3 megabases along a chromosome. The correlations are of strong statistical significance for almost all 43 chromosomal arms. Our results clearly show that Giemsa-dark bands are locally GC-poor regions compared with the flanking regions. These findings are consistent with the model that matrix-associated regions, which are known to be AT-rich, are present more densely in Giemsa-dark bands than in -light bands.
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Real-time fluorescence analysis on molecular mechanisms for regulation of cytochrome P450scc activity upon steroidogenic stimulation in adrenocortical cells 査読あり
Ryota Homma, Tetsuya Kimoto, Yoshihito Niimura, Alexander Krivosheev, Takayuki Hara, Yoshihiro Ohta, Suguru Kawato
Journal of Inorganic Biochemistry 82 ( 1-4 ) 171 - 180 2000年
記述言語：英語 掲載種別：研究論文（学術雑誌）
Real-time fluorescence analysis revealed that the activity of cytochrome P450scc was related to Ca2+ signals arising from extracellular NADPH, ACTH and ATP stimulation in adrenocortical fasciculata cells. The side-chain cleavage reaction by cytochrome P450scc was measured with 3β-hydroxy-22,23-bisnor-5-cholenyl ether (cholesterol-resorufin) by observing the distinct increase in fluorescence upon conversion of cholesterol-resorufin to resorufin and pregnenolone. Adrenocorticotropic hormone (ACTH) induced a relatively small stimulation of the P450scc activity. A significant production of resorufin was revealed after stimulation of cell cultures with 100 pM, 1 nM of ACTH for 3 h. On the other hand, extracellular NADPH was found to rapidly and greatly stimulate the resorufin production in intact cells immediately after the addition of 50-500 μM NADPH. The extracellular NADPH stimulation was prevented by the addition of thapsigargin and EGTA which abolished Ca2+ oscillations induced by NADPH. Suramin, a specific antagonist of the P(2y) type ATP receptor, also completely abolished the NADPH-induced cholesterol-resorufin conversion. These results imply that extracellular NADPH (membrane impermeable) produced Ca2+ oscillations through its binding to ATP receptor thereby stimulating the activity of P450scc. The application of 45-500 μM extracellular ATP to cells did not, however, significantly increase the resorufin production. These three stimulators produced very different types of Ca2+ signals. ACTH induced mainly a series of Ca2+ spikes superimposed on a long-lasting basal Ca2+ elevation. The Ca2+ signals induced by NADPH showed predominantly a series of Ca2+ spikes without elevation of the basal Ca2+ concentration. Only long-lasting Ca2+ elevation was induced by extracellular ATP. The stimulation of cytochrome P450scc may thus be correlated with the different patterns of Ca2+ signals. Copyright (C) 2000 Elsevier Science B.V.
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Module-intron correlation and intron sliding in family F/10 xylanase genes 査読あり
Y Sato, Y Niimura, K Yura, M Go
GENE 238 ( 1 ) 93 - 101 1999年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：ELSEVIER SCIENCE BV
Xylanases are classified into two families, numbered F/10 and G/11 according to the similarity of amino acid sequences of their catalytic domain (Henrissat, B., Bairoch, A., 1993. New families in the classification of glycosyl hydrolases based on amino acid sequence similarities. Biochem. J. 293, 781-788). Three-dimensional structure of the catalytic domain of the family F/10 xylanase was reported (White, A., Withers, S.G., Gilkes, N.R., Rose, D.R., 1994. Crystal structure of the catalytic domain of the beta-1,4-glycanase Cex from Cellulomonas fimi. Biochemistry 33, 12546-12552). The domain was decomposed into 22 modules by centripetal profiles (Gb, M., Nosaka, M., 1987. Protein architecture and the origin of introns. Cold Spring Harbor Symp. Quant. Biol. 52, 915-924; Noguti, T., Sakakibara, H., Gb, M., 1993. Localization of hydrogen-bonds within modules in barnase. Proteins 16, 357-363). A module is a contiguous polypeptide segment of amino acid residues having a compact conformation within a globular domain. Collected 31 intron sites of the family F/10 xylanase genes from fungus were found to be correlated to module boundaries with considerable statistical force (p values <0.001). The relationship between the intron locations and protein structures provides supporting evidence for the ancient origin of introns, because such a relationship cannot be expected by random insertion of introns into eukaryotic genes, but it rather suggests pre-existence of introns in the ancestral genes of prokaryotes and eukaryotes. A phylogenetic tree of the fungal and bacterial xylanase sequences made two clusters; one includes both the bacterial and fungal genes, but the other consists of only fungal genes. The mixed cluster of bacterial genes without introns and the fungal genes with introns further supports the ancient origin of introns. Comparison of the conserved base sequences of introns indicates that sliding of a splice site occurred in Aspergillus kawachii gene by one base from the ancestral position. Substrate-binding sites of xylanase are localized on eight modules, and introns are found at both termini of six out of these functional modules. This result suggests that introns might play a functional role in shuffling the exons encoding the substrate-binding modules. (C) 1999 Elsevier Science B.V. All rights reserved.
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Time-resolved study of effect of chlorpromazine on mobility of cytochrome P-450 and phospholipids in the inner membrane of adrenocortical mitochondria 査読あり
Ryota Homma, Tsutomu Kouyama, Makoto Yamada, Yoshihito Niimura, Alexander V. Krivosheev, Takayuki Hara, Suguru Kawato
Journal of Pharmaceutical and Biomedical Analysis 15 ( 9-10 ) 1215 - 1222 1997年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
The effects of chlorpromazine on the mobility of cytochrome P-450 and the fluidity of lipid membranes have been investigated in bovine adrenocortical submitochondrial particles (SMP). Rotational diffusion of the cytochrome was measured by observing the decay of absorption anisotropy, r(a)(t), after photolysis of the heme CO complex by a vertically polarized laser flash. Analysis of r(a)(t) was based on a 'rotation-about-membrane-normal' model. The anisotropy decayed within 2 ms to a time independent value r3. The presence of chlorpromazine decreased the mobile population of cytochrome P-450 from 28 to 23%. The rotational relaxation time Φ(a), of the mobile population (~ 1100 μs) was, however, not significantly changed by chlorpromazine. The lipid fluidity was examined by observing time-resolved fluorescence anisotropy, r(f)(t), of 1,6-diphenyl 1,3,5-hexatriene (DPH). The anisotropy r(f)(t) decayed within 70 ns to a time independent value r(∞). The motion of DPH was analyzed based on a 'wobbling-in-cone' model. The presence of chlorpromazine decreased the cone angle from 42°to 39°, while the rotational relaxation time Φ(f), (~ 2 ns) was not significantly changed by the presence of chlorpromazine. These results demonstrate that chlorpromazine decreased the mobility of not only lipids but also membrane proteins.