Dataset Information

Rapid Expansion of Phenylthiocarbamide Non-Tasters among Japanese Macaques.

ABSTRACT: 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.

SUBMITTER: Suzuki-Hashido N

PROVIDER: S-EPMC4511751 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Rapid Expansion of Phenylthiocarbamide Non-Tasters among Japanese Macaques.

Suzuki-Hashido Nami N Hayakawa Takashi T Matsui Atsushi A Go Yasuhiro Y Ishimaru Yoshiro Y Misaka Takumi T Abe Keiko K Hirai Hirohisa H Satta Yoko Y Imai Hiroo H

PloS one 20150722 7

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 ...[more]

PMID: 26201026

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Project description:UnlabelledIn 2001-2002, six of seven Japanese macaques (Macaca fuscata) died after developing hemorrhagic syndrome at the Kyoto University Primate Research Institute (KUPRI). While the cause of death was unknown at the time, we detected simian retrovirus 4 (SRV-4) in samples obtained from a similar outbreak in 2008-2011, during which 42 of 43 Japanese macaques died after exhibiting hemorrhagic syndrome. In this study, we isolated SRV-4 strain PRI-172 from a Japanese macaque showing severe thrombocytopenia. When inoculated into four Japanese macaques, the isolate induced severe thrombocytopenia in all within 37 days. We then constructed an infectious molecular clone of strain PRI-172, termed pSR415, and inoculated the clone-derived virus into two Japanese macaques. These animals also developed severe thrombocytopenia in just 31 days after inoculation, and the virus was reisolated from blood, bone marrow, and stool. At necropsy, we observed bleeding from the gingivae and subcutaneous bleeding in all animals. SRV-4 infected a variety of tissues, especially in digestive organs, including colon and stomach, as determined by real-time reverse transcription-PCR (RT-PCR) and immunohistochemical staining. Furthermore, we identified the SRV-4 receptor as ASCT2, a neutral amino acid transporter. ASCT2 mRNA was expressed in a variety of tissues, and the distribution of SRV-4 proviruses in infected Japanese macaques correlated well with the expression levels of ASCT2 mRNA. From these results, we conclude that the causative agent of hemorrhagic syndrome in KUPRI Japanese macaques was SRV-4, and its receptor is ASCT2.ImportanceDuring two separate outbreaks at the KUPRI, in 2001-2002 and 2008-2011, 96% of Japanese macaques (JM) that developed an unknown hemorrhagic syndrome died. Here, we isolated SRV-4 from a JM developing thrombocytopenia. The SRV-4 isolate and a molecularly cloned SRV-4 induced severe thrombocytopenia in virus-inoculated JMs within 37 days. At necropsy, we observed bleeding from gingivae and subcutaneous bleeding in all affected JMs and reisolated SRV-4 from blood, bone marrow, and stool. The distribution of SRV-4 proviruses in tissues correlated with the mRNA expression levels of ASCT2, which we identified as the SRV-4 receptor. From these results, we conclude that SRV-4 was the causative agent of hemorrhagic syndrome in JMs in KUPRI.

Dataset Information

Rapid Expansion of Phenylthiocarbamide Non-Tasters among Japanese Macaques.

Publications

Rapid Expansion of Phenylthiocarbamide Non-Tasters among Japanese Macaques.

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