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