Comparative Genetics of Sweet Taste in Carnivora

食肉动物甜味的比较遗传学

• 批准号: 8196944
• 负责人: PeiHua Jiang
• 金额: $ 33.86万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8196944
• 关键词: Affect; Ailurus; Amino Acid Sequence; Animals; Aspartame; Behavior; Behavioral; Binding; Binding Sites; Biological Assay; Carbohydrates; Carnivora; Cells; Chimera organism; Code; Complementary DNA; Cyclamates; DNA Sequence; Data; Diabetes Mellitus; Diet; Docking; Family; Felis catus; Ferrets; Food; Fossa; Fructose; Galactose; Gene Family; Genes; Genetic; Genets; Genotype; Giant Pandas; Glucose; Goals; Human; Hyena; Intervention; Lactose; Ligands; Maltose; Mammals; Methods; Modeling; Molecular; Molecular Models; Nature; Obesity; Odobenus rosmarus; Outcomes Research; Pattern; Perception; Phenotype; Phoca vitulina; Physical Fitness; Prevalence; Receptor Gene; Red Wolf; Research; Saccharin; Sea Lions; Site; Solutions; South American; Specificity; Spottings; Stimulus; Striped Skunk; Structure; Structure-Activity Relationship; Sucrose; Sweetening Agents; Symptoms; System; T1R receptor; Taste Perception; Techniques; Testing; Variant; Water; base; behavior observation; behavior test; comparative; design; drinking; fitness; in vitro testing; insight; interest; member; microdeletion; molecular modeling; neotame; next generation; preference; public health relevance; receptor; receptor binding; response; species difference; sugar; sweet receptor; sweet taste perception; trichlorosucrose

DESCRIPTION (provided by applicant): The liking of sweetness probably evolved to maximize the evolutionary fitness of humans, but it now detracts from our physical fitness, increasing the prevalence of obesity (which is due in part to the overconsumption of sweet, calorie-rich foods) and exacerbating the symptoms of diabetes. Other animal species also like sweet foods and drinks, and therefore we propose a comparative approach to study the preference for sweetness and taste receptors (T1R family) using closely related animal species that differ markedly in their behavior toward sweet taste. Specifically, we will study members of the Order Carnivora because they provide a wide range of sweet taste behavior and because preliminary results suggest a mechanism for these species differences: cats do not like sugar and also have a microdeletion in one subunit of the sweet receptor gene that renders it nonfunctional. Additional preliminary data suggest that other Carnivora species that have a functional sweet receptor also have a preference for sugars but do not show preferences for high-intensity sweeteners (with some interesting exceptions). In the research we propose here, we will test the hypothesis that the structure and function of sweet taste receptors in Carnivora species affect species-specific taste preferences, and that these in turn are reflected in species food choices. In Aim 1 we will sequence the genes for all three members of the T1R taste receptor family, Tas1r1, Tas1r2, and Tas1r3, from 15 Carnivora species (meerkat, domestic cat, ferret, genet, lesser and giant panda, South American coati, walrus, Pacific Harbor seal, sea lion, spotted hyena, red wolf, striped skunk, fossa, and banded linsang). In Aim 2 we will perform behavioral studies of these same species to evaluate their behavioral responses to 12 sweet stimuli: six natural sugars and six high-intensity sweeteners In Aim 3, we will functionally express the receptor genes of these Carnivora species in a cell- based assay system (based on data obtained in Aim 1 and 2). The patterns of differences among these species will help us identify the structural features of taste receptors that underlie their binding specificity for sugars, high-intensity sweeteners, and potentially other compounds. Results of this research will provide new insights into the nature and function of taste receptor genes and how their variation affects taste perception, thereby adding to our understanding of the molecular basis of the human sweet tooth. PUBLIC HEALTH RELEVANCE: Like many genes, those coding for the sweet receptor are highly conserved among mammals, but the sites where animals differ in amino acid sequence are related to their unique taste preferences and habitual diets. By examining the variations in DNA sequence among diverse species of Carnivora, some of which are indifferent to sweet and some of which are avid sweet- likers, the structure of the receptor and its function can be better understood, leading to interventions to palliate the human overconsumption of sweet carbohydrates.

描述(申请人提供)：喜欢甜食可能是为了最大限度地提高人类进化的适宜性，但现在它损害了我们的身体健康，增加了肥胖的患病率(部分原因是过度食用甜食和高热量食物)，并加剧了糖尿病的症状。其他动物物种也喜欢甜食和饮料，因此我们提出了一种比较的方法，利用对甜味的行为明显不同的密切相关动物物种来研究对甜味和味觉受体(T1R家族)的偏好。具体地说，我们将研究食肉目的成员，因为它们提供了广泛的甜味行为，而且因为初步结果表明了这些物种差异的机制：猫不喜欢糖，而且甜味受体基因的一个亚单位存在微缺失，使其失去功能。更多的初步数据表明，其他具有功能性甜味受体的食肉动物物种也对糖有偏好，但对高强度甜味剂没有表现出偏好(除了一些有趣的例外)。在我们在这里提出的研究中，我们将检验这样一个假设，即食肉动物甜味受体的结构和功能影响物种特定的口味偏好，并反过来反映在物种的食物选择中。在目标1中，我们将对T1R味觉受体家族的所有三个成员Tas1r1、Tas1r2和Tas1r3的基因进行测序，这些成员来自15个食肉动物物种(猫鼬、家猫、雪貂、基尼特、小熊猫和大熊猫、南美考亚科动物、海象、太平洋海豹、海狮、斑点鬣狗、红狼、条纹臭鼬、佛萨和环带林桑)。在目标2中，我们将对这些物种进行行为研究，以评估它们对12种甜味刺激的行为反应：6种天然糖和6种高强度甜味剂。在目标3中，我们将在基于细胞的测试系统中功能性地表达这些食肉动物物种的受体基因(基于在目标1和2中获得的数据)。这些物种之间的差异模式将有助于我们确定味觉受体的结构特征，这些结构特征是它们与糖、高强度甜味剂和潜在的其他化合物结合的特异性的基础。这项研究的结果将为味觉受体基因的性质和功能以及它们的变异如何影响味觉提供新的见解，从而增加我们对人类爱吃甜食的分子基础的理解。 与公共健康相关：与许多基因一样，这些编码甜味受体的基因在哺乳动物中高度保守，但动物氨基酸序列不同的位置与它们独特的口味偏好和习惯性饮食有关。通过研究不同食肉动物物种之间的DNA序列差异，可以更好地了解受体的结构和功能，从而进行干预，以缓解人类对甜味碳水化合物的过度消费。