Ezran Camille, Karanewsky Caitlin J, Pendleton Jozeph L, Sholtz Alex, Krasnow Maya R, Willick Jason, Razafindrakoto Andriamahery, Zohdy Sarah, Albertelli Megan A, Krasnow Mark A
Department of Biochemistry.
Howard Hughes Medical Institute, and.
Genetics. 2017 Jun;206(2):651-664. doi: 10.1534/genetics.116.199448.
Systematic genetic studies of a handful of diverse organisms over the past 50 years have transformed our understanding of biology. However, many aspects of primate biology, behavior, and disease are absent or poorly modeled in any of the current genetic model organisms including mice. We surveyed the animal kingdom to find other animals with advantages similar to mice that might better exemplify primate biology, and identified mouse lemurs ( spp.) as the outstanding candidate. Mouse lemurs are prosimian primates, roughly half the genetic distance between mice and humans. They are the smallest, fastest developing, and among the most prolific and abundant primates in the world, distributed throughout the island of Madagascar, many in separate breeding populations due to habitat destruction. Their physiology, behavior, and phylogeny have been studied for decades in laboratory colonies in Europe and in field studies in Malagasy rainforests, and a high quality reference genome sequence has recently been completed. To initiate a classical genetic approach, we developed a deep phenotyping protocol and have screened hundreds of laboratory and wild mouse lemurs for interesting phenotypes and begun mapping the underlying mutations, in collaboration with leading mouse lemur biologists. We also seek to establish a mouse lemur gene "knockout" library by sequencing the genomes of thousands of mouse lemurs to identify null alleles in most genes from the large pool of natural genetic variants. As part of this effort, we have begun a citizen science project in which students across Madagascar explore the remarkable biology around their schools, including longitudinal studies of the local mouse lemurs. We hope this work spawns a new model organism and cultivates a deep genetic understanding of primate biology and health. We also hope it establishes a new and ethical method of genetics that bridges biological, behavioral, medical, and conservation disciplines, while providing an example of how hands-on science education can help transform developing countries.
在过去50年里,对少数几种不同生物进行的系统遗传学研究改变了我们对生物学的理解。然而,灵长类生物学、行为和疾病的许多方面在包括小鼠在内的任何当前遗传模型生物中都不存在或模拟得很差。我们调查了动物界,以寻找其他具有与小鼠类似优势的动物,这些动物可能能更好地体现灵长类生物学特征,并确定小鼠狐猴(属)是杰出的候选者。小鼠狐猴是原猴亚目灵长类动物,与小鼠和人类的遗传距离大致为一半。它们是世界上最小、发育最快、繁殖力最强且数量最多的灵长类动物之一,分布在马达加斯加全岛,由于栖息地破坏,许多处于单独的繁殖种群中。它们的生理学、行为和系统发育在欧洲的实验室群体以及马达加斯加雨林的实地研究中已经研究了几十年,最近还完成了高质量的参考基因组序列。为了启动经典遗传学方法,我们开发了一种深度表型分析方案,并与领先的小鼠狐猴生物学家合作,筛选了数百只实验室和野生小鼠狐猴以寻找有趣的表型,并开始对潜在突变进行定位。我们还试图通过对数千只小鼠狐猴的基因组进行测序来建立一个小鼠狐猴基因“敲除”文库,以便从大量自然遗传变异中识别大多数基因中的无效等位基因。作为这项工作的一部分,我们已经启动了一个公民科学项目,马达加斯加各地的学生探索他们学校周围非凡的生物学,包括对当地小鼠狐猴的纵向研究。我们希望这项工作能催生一种新的模型生物,并培养对灵长类生物学和健康的深入遗传学理解。我们还希望它能建立一种新的、符合伦理的遗传学方法,将生物学、行为学、医学和保护学科联系起来,同时提供一个实践科学教育如何有助于改变发展中国家的例子。