Nature：气味感知基因决定人对气味的不同感受

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生物谷报道：美国杜克大学和洛克菲勒大学研究人员16日发表报告称，人体的一种气味感知基因决定着人们对人体汗液气味的“看法”。人类对气味的感受为何会存在个体差异的谜团就此揭开。

　最新突破

　这项研究结果于16日在《自然》杂志网站上公布。由于它认为人类气味感知基因决定着人们对气味的不同感受，这项研究成果成为生物学气味感知研究领域的一大突破。

　研究人员从人体汗液中的雄脂酮入手，成功找出造成人类气味感受个体差异的关键因素——气味感知基因。

　雄脂酮是睾丸激素分解后形成的一种化学成分，通常存在于男性和女性分泌的汗液中，但在男性汗液中的含量更高。

　杜克大学研究人员松南宏明(音译)和同事首先选择了400种已知能够辨别气味的感知基因，并对它们中分辨男性汗液气味的化学成分进行研究。

　他们随后发现，一种名为OR7D4的基因表现“抢眼”，对随汗液分泌的男性荷尔蒙雄脂酮反应强烈。

　个体差异

　研究人员采集了洛克菲勒大学“气味感受”测试中400名测试者的血样，对他们的脱氧核糖核酸(DNA)进行排序比对，以证明人们对男性汗液中雄脂酮气味的感受不同是否由OR7D4的个体差异导致。

　功夫不负有心人。研究人员最终发现，基因OR7D4的个体差异决定着人们对雄脂酮气味的感受。这也正是为什么对于同一种汗液，有人会觉得刺鼻，有人会觉得像香草般香甜，而有人则什么感觉也没有。

　松南宏明在接受路透社采访时说，人们会对随汗液分泌的雄脂酮产生不同感受是不争的事实，但将人类气味感知基因与它联系起来尚属首次。

　松南宏明表示，研究将继续下去，并逐步扩展深入。例如，研究人员将进一步研究雄脂酮与人类性行为和社会行为之间的关系，看看气味究竟如何影响人类行为。（今晚报）

原始出处：

Nature advance online publication 16 September 2007 | doi:10.1038/nature06162; Received 20 June 2007; Accepted 8 August 2007; Published online 16 September 2007

Genetic variation in a human odorant receptor alters odour perception

Andreas Keller1,4, Hanyi Zhuang2,4, Qiuyi Chi2, Leslie B. Vosshall1 & Hiroaki Matsunami2,3

Laboratory of Neurogenetics and Behaviour, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA
Department of Molecular Genetics and Microbiology, and,
Department of Neurobiology, Duke University Medical Centre, Research Drive, Durham, North Carolina 27710, USA
These authors contributed equally to this work.

Correspondence to: Leslie B. Vosshall1Hiroaki Matsunami2,3 Correspondence and requests for materials should be addressed to H.M. (Email: hiroaki.matsunami@duke.edu) and L.B.V.

Human olfactory perception differs enormously between individuals, with large reported perceptual variations in the intensity and pleasantness of a given odour. For instance, androstenone (5 alpha -androst-16-en-3-one), an odorous steroid derived from testosterone, is variously perceived by different individuals as offensive ("sweaty, urinous"), pleasant ("sweet, floral") or odourless1, 2, 3. Similar variation in odour perception has been observed for several other odours4, 5, 6. The mechanistic basis of variation in odour perception between individuals is unknown. We investigated whether genetic variation in human odorant receptor genes accounts in part for variation in odour perception between individuals7, 8. Here we show that a human odorant receptor, OR7D4, is selectively activated in vitro by androstenone and the related odorous steroid androstadienone (androsta-4,16-dien-3-one) and does not respond to a panel of 64 other odours and two solvents. A common variant of this receptor (OR7D4 WM) contains two non-synonymous single nucleotide polymorphisms (SNPs), resulting in two amino acid substitutions (R88W, T133M; hence 'RT') that severely impair function in vitro. Human subjects with RT/WM or WM/WM genotypes as a group were less sensitive to androstenone and androstadienone and found both odours less unpleasant than the RT/RT group. Genotypic variation in OR7D4 accounts for a significant proportion of the valence (pleasantness or unpleasantness) and intensity variance in perception of these steroidal odours. Our results demonstrate the first link between the function of a human odorant receptor in vitro and odour perception.