Atsushi Matsui

Degeneration of Olfactory Receptor Gene Repertories in Primates: No Direct Link to Full Trichromatic Vision

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.

Frequent Expansions of the Bitter Taste Receptor Gene Repertoire during Evolution of Mammals in the Euarchontoglires Clade

Genome studies of mammals in the superorder Euarchontoglires (a clade that comprises the orders Primates, Dermoptera, Scandentia, Rodentia, and Lagomorpha) are important for understanding the biological features of humans, particularly studies of medical model animals such as macaques and mice. Furthermore, the dynamic ecoevolutionary signatures of Euarchontoglires genomes may be discovered because many species in this clade are characterized by their successful adaptive radiation to various ecological niches. In this study, we investigated the evolutionary trajectory of bitter taste receptor genes (TAS2Rs) in 28 Euarchontoglires species based on homology searches of 39 whole-genome assemblies. The Euarchontoglires species possessed variable numbers of intact TAS2Rs, which ranged from 16 to 40, and their last common ancestor had at least 26 intact TAS2Rs. The gene tree showed that there have been at least seven lineage-specific events involving massive gene duplications. Gene duplications were particularly evident in the ancestral branches of anthropoids (the anthropoid cluster), which may have promoted the adaptive evolution of anthropoid characteristics, such as a trade-off between olfaction and other senses and the development of herbivorous characteristics. Subsequent whole-gene deletions of anthropoid cluster TAS2Rs in hominoid species suggest ongoing ectopic homologous recombination in the anthropoid cluster. These findings provide insights into the roles of adaptive sensory evolution in various ecological niches and important clues related to the molecular mechanisms that underlie taste diversity in Euarchontoglires mammalian species, including humans.

Identification of non-taster Japanese macaques for a specific bitter taste

Bitter taste perception evolved as a key detection mechanism against the ingestion of bioactive substances, and is mediated by TAS2R gene family members in vertebrates. The most widely known and best studied bitter substance is phenylthiocarbamide (PTC), which is recognized by TAS2R38 and has a molecular structure similar to that of glucosinolates contained in Brassica plants. The “non-taster” phenotypic polymorphism (i.e., not sensitive to PTC-containing foods) has been identified in many primates, including humans. Here, we report genetic and behavioral evidence for the existence of “non-taster” Japanese macaques, which originated from a restricted region of Japan. Comparison of the sequences of the TAS2R38 gene of 333 Japanese and 55 rhesus macaques suggested that this genotype appeared after the divergence of these two species, independently of the appearance of human and chimpanzee “non-tasters”. This finding might give a clue for elucidating the ecological, evolutionary, and neurobiological aspects of bitter taste perception of primates, as related to the plants that they sometimes use as foods in their habitats.

Stability of Mitochondrial Membrane Proteins in Terrestrial Vertebrates Predicts Aerobic Capacity and Longevity

The cellular energy produced by mitochondria is a fundamental currency of life. However, the extent to which mitochondrial (mt) performance (power and endurance) is adapted to habitats and life strategies of vertebrates is not well understood. A global analysis of mt genomes revealed that hydrophobicity (HYD) of mt membrane proteins (MMPs) is much lower in terrestrial vertebrates than in fishes and shows a strong negative correlation with serine/threonine composition (STC). Here, we present evidence that this systematic feature of MMPs was crucial for the evolution of large terrestrial vertebrates with high aerobic capacity. An Arrhenius-type equation gave positive correlations between STC and maximum life span (MLS) in terrestrial vertebrates (with a few exceptions relating to the lifestyle of small animals with a high resting metabolic rate [RMR]) and negative correlations in secondary marine vertebrates, such as cetaceans and alligators (which returned from land to water, utilizing buoyancy with increased body size). In particular, marked STC increases in primates (especially hominoids) among placentals were associated with very high MLS values. We connected these STC increases in MMPs with greater stability of respiratory complexes by estimating the degradation of the Arrhenius plot given by accelerating mtRMR up to mt maximum metabolic rate. Both mtRMR and HYD in terrestrial vertebrates decreased with increasing body mass. Decreases in mtRMR raise MMP stability when high mobility is not required, whereas decreased HYD may weaken this stability under the hydrophobic environment of lipid bilayer. High maximal metabolic rates (5–10 RMR), which we postulate require high MMP mobility, presumably render MMPs more unstable. A marked rise in STC may therefore be essential to stabilize MMPs, perhaps as dynamic supercomplexes, via hydrogen bonds associated with serine/threonine motifs.

Molecular Phylogeny and Evolution in Primates

Primate evolution draws special attention because of its direct relevance to human origins. However, there are still several phylogenetic problems remaining among the primates. Recent molecular evolution studies using nuclear and mitochondrial DNA data seem to have established a consensus with respect to the phylogenetic positions of various primates. In addition, the presence/absence patterns of the short interspersed elements (SINE), which are regarded to be informative molecular cladistic markers, strongly supported the phylogenetic placement of several problematic species. Although the phylogenetic relationships of living primate species are relatively well established, the divergence times among them are still controversial. This controversy has arisen partly because different authors have used different molecular data with different methods and calibration points. Here, we review recent molecular phylogenetic studies of primates together with our own study. Furthermore, we compare and discuss the divergence times estimated for various primate species.

Emergence of infectious malignant thrombocytopenia in Japanese macaques ( Macaca fuscata ) by SRV-4 after transmission to a novel host

We discovered a lethal hemorrhagic syndrome arising from severe thrombocytopenia in Japanese macaques kept at the Primate Research Institute, Kyoto University. Extensive investigation identified that simian retrovirus type 4 (SRV-4) was the causative agent of the disease. SRV-4 had previously been isolated only from cynomolgus macaques in which it is usually asymptomatic. We consider that the SRV-4 crossed the so-called species barrier between cynomolgus and Japanese macaques, leading to extremely severe acute symptoms in the latter. Infectious agents that cross the species barrier occasionally amplify in virulence, which is not observed in the original hosts. In such cases, the new hosts are usually distantly related to the original hosts. However, Japanese macaques are closely related to cynomolgus macaques, and can even hybridize when given the opportunity. This lethal outbreak of a novel pathogen in Japanese macaques highlights the need to modify our expectations about virulence with regards crossing species barriers.

Rapid Expansion of Phenylthiocarbamide Non-Tasters among Japanese Macaques.

Bitter taste receptors (TAS2R proteins) allow mammals to detect and avoid ingestion of toxins in food. Thus, TAS2Rs play an important role in food choice and are subject to complex natural selection pressures. In our previous study, we examined nucleotide variation in TAS2R38, a gene expressing bitter taste receptor for phenylthiocarbamide (PTC), in 333 Japanese macaques (Macaca fuscata) from 9 local populations in Japan. We identified a PTC “non-taster” TAS2R38 allele in Japanese macaques that was caused by a loss of the start codon. This PTC non-taster allele was only found in a limited local population (the Kii area), at a frequency of 29%. In this study, we confirmed that this allele was present in only the Kii population by analyzing an additional 264 individuals from eight new populations. Using cellular and behavioral experiments, we found that this allele lost its receptor function for perceiving PTC. The nucleotide sequences of the allele including flanking regions (of about 10 kb) from 23 chromosomes were identical, suggesting that a non-taster allele arose and expanded in the Kii population during the last 13,000 years. Genetic analyses of non-coding regions in Kii individuals and neighboring populations indicated that the high allele frequency in the Kii population could not be explained by demographic history, suggesting that positive selection resulted in a rapid increase in PTC non-tasters in the Kii population. The loss-of-function that occurred at the TAS2R38 locus presumably provided a fitness advantage to Japanese macaques in the Kii population. Because TAS2R38 ligands are often found in plants, this functional change in fitness is perhaps related to feeding habit specificity. These findings should provide valuable insights for elucidating adaptive evolutionary changes with respect to various environments in wild mammals.

Positive selection on schizophrenia-associated ST8SIA2 gene in post-glacial Asia

A number of loci are associated with highly heritable schizophrenia and the prevalence of this mental illness has had considerable negative fitness effects on human populations. Here we focused on one particular schizophrenia-associated gene that encodes a sialyltransferase (ST8SIA2) and is expressed preferentially in the brain with the level being largely determined by three SNPs in the promoter region. It is suggested that the expression level of the ST8SIA2 gene is a genetic determinant of schizophrenia risk, and we found that a geographically differentiated non-risk SNP type (CGC-type) has significantly reduced promoter activity. A newly developed method for detecting ongoing positive selection was applied to the ST8SIA2 genomic region with the identification of an unambiguous sweep signal in a rather restricted region of 18 kb length surrounding the promoter. We also found that while the CGC-type emerged in anatomically modern humans in Africa over 100 thousand years ago, it has increased its frequency in Asia only during the past 20–30 thousand years. These findings support that the positive selection is driven by psychosocial stress due to changing social environments since around the last glacial maximum, and raise a possibility that schizophrenia extensively emerged during the Upper Paleolithic and Neolithic era.

A Quill Vibrating Mechanism for a Sounding Apparatus in the Streaked Tenrec (Hemicentetes semispinosus)

The streaked tenrec (Hemicentetes semispinosus) is equipped with a quill vibrating mechanism on the dorsal side of the caudal trunk that has evolved as an extraordinary sounding apparatus for communication. An arrangement of 15 or 16 light-brown quills was observed. Thickened cutaneous muscles were confirmed beneath quills. We named this structure the “quill vibrator disc” (QVD). The QVD was 16.8 mm long and 8.55 mm wide in a typical adult. Longitudinal musculature symmetrical about the sagittal plane was developed in the QVD. Myocytes were found immunohistochemically to contain mainly fast myosin but not slow myosin. These findings indicate that the QVD is a specialized apparatus in the cutaneous muscle that contributes to the vibration of quills and to the production of sound for communication.

Polymorphisms in the GPCRs of primates and the genetic database on the individual primates in the Primate Research Institute

Neuronal population of the olfactory epithelium required for nipple search and subsequent suckling behavior was examined in developing rats of the suckling period. After unilateral ablation of the olfactory bulb, different concentrations of ZnSO4 were contralaterally injected into the nasal cavity to produce varying degrees of neuronal degeneration in the olfactory epithelium. The ZnSO4-treated pups were divided into two groups with and without suckling, and the numbers of the intact olfactory receptor neurons in the olfactory epithelium were counted in each animal immunohistochemically using an antibody for olfactory marker protein, a marker protein for olfactory receptor neurons. We will provide quantitative data showing the minimal neuronal population essential for suckling at the olfactory epithelial level in the rats of the different developmental stages.