Collaborative research: Genotypic and phenotypic changes associated with encephalization

合作研究：与脑化相关的基因型和表型变化

• 批准号: 0550209
• 负责人: Lawrence Grossman
• 金额: $ 44.66万
• 依托单位: Wayne State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-15 至 2012-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0550209&HistoricalAwards=false
• 关键词: Collaborative; research; Genotypic; phenotypic; changes

This research team is elucidating the genetic changes that orchestrated the expansion of the brain's neocortex during humankind's ancestry. This interdisciplinary team of scientists has compiled a list of genes that are important for the brain's anatomical development or its biochemical functioning. By utilizing the comparative genomic sequence data that are publicly available, the investigators are identifying in their list of brain-important genes those showing evidence of adaptive change in humankind's ancestry. The investigators intend to find out if such adaptive change is indeed associated with encephalization, the process that brought about brains with marked neocortical enlargements and increased cognitive capacities. To do so, the comparative gene sequence data will be enlarged to include a selection of other primates and other mammals. The species selected will allow testing of the hypothesis that those brain-important genes showing adaptive change in the lineage to humans will also show a higher frequency of adaptive change in non-human lineages where encephalization increased than in lineages where encephalization did not increase. For example, the investigators will compare the encephalized bottle-nosed dolphin (Tursiops truncatus) to the less encephalized odontocete sperm whale (Physeter macrocephalus) and mysticete blue whale (Balaenoptera musculus). In addition to the gene data, other types of molecular data on encephalization will also be gathered. To this end, the investigators will use immunohistochemical techniques to determine whether particular neuroanatomical structures show increasing levels of activity for genes involved in aerobic energy production in the series of macaques, chimpanzees and humans, a result that would correlate with the marked expansion of the neocortex in the human lineage. A database of neocortical phenotypic features will be constructed for a diverse range of primates and other mammals in order to search for cortical histological features that characterize the emergence of brains with increased cognitive capacities. Broader impacts include the establishment of a web site to disseminate these genotypic and phenotypic data that distinguish encephalized from non-encephalized lineages. Taken together, this work will further our goal of identifying the genetic underpinnings of humankind and determining which of the underpinnings are truly unique for humans. The interdisciplinary team of primatologists, biochemical geneticists, neuroscientists and anthropologists bridges diverse disciplines in order to elucidate the linked genotypic-phenotypic changes that shaped the human brain. By yielding a more objective view of the biological place of humans in nature, this research should have broad societal impact. Identifying the genetic changes that shaped the human brain could prove to be of great value in the search for new therapeutic agents in the field of mental health.

该研究小组正在阐明人类祖先时期大脑新皮质扩张的基因变化。这个跨学科的科学家团队编制了一份对大脑的解剖发育或其生化功能很重要的基因列表。通过利用公开的比较基因组序列数据，研究人员正在他们的大脑重要基因列表中识别出那些显示人类祖先适应性变化证据的基因。研究人员打算查明这种适应性变化是否确实与脑化有关，脑化是大脑新皮质显着增大和认知能力增强的过程。为此，比较基因序列数据将被扩大以包括选择的其他灵长类动物和其他哺乳动物。所选物种将允许测试以下假设：那些在人类谱系中显示出适应性变化的大脑重要基因，在脑化增加的非人类谱系中也将显示出比脑化不增加的谱系更高的适应性变化频率。例如，研究人员将脑化的宽吻海豚（Tursiops truncatus）与脑化程度较低的齿鲸抹香鲸（Physeter Macrocephalus）和须鲸蓝鲸（Balaenoptera musculus）进行比较。除了基因数据外，还将收集有关脑化的其他类型的分子数据。为此，研究人员将使用免疫组织化学技术来确定在一系列猕猴、黑猩猩和人类中，特定的神经解剖结构是否显示出参与有氧能量产生的基因的活性水平增加，这一结果将与新皮质的显着扩张相关。在人类血统中。将为各种灵长类动物和其他哺乳动物构建新皮质表型特征数据库，以寻找表征认知能力增强的大脑出现的皮质组织学特征。更广泛的影响包括建立一个网站来传播这些区分脑化谱系和非脑化谱系的基因型和表型数据。总而言之，这项工作将进一步推进我们的目标，即确定人类的遗传基础，并确定哪些基础对于人类来说是真正独特的。由灵长类动物学家、生化遗传学家、神经科学家和人类学家组成的跨学科团队将不同学科联系起来，以阐明塑造人类大脑的相关基因型-表型变化。通过对人类在自然界中的生物学地位产生更客观的看法，这项研究应该会产生广泛的社会影响。识别塑造人类大脑的基因变化对于寻找心理健康领域的新治疗药物具有重要价值。