Neanderthal-Derived Genetic Variation is Associated with Functional Connectivity in the Brains of Living Humans
Neanderthal-Derived Genetic Variation is Associated with Functional Connectivity in the Brains of Living Humans
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DOI：
10.1089/brain.2020.0809
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发表时间：
2021-02-01
影响因子：
3.4
通讯作者：
Berman, Karen F.
中科院分区：
文献类型：
--
作者：
Gregory, Michael D.;Kippenhan, J. Shane;Berman, Karen F.
目的：确定源自尼安德特人的遗传变异是否与现代人类大脑的功能连接模式有关。简介：近 5 万年前，尼安德特人与现代人类的祖先杂交，留下了延续至今的遗传遗产。这种源自尼安德特人的遗传变异的痕迹此前已被证明富含编码神经发生和髓鞘形成的基因，并改变了活人的头骨形状和大脑结构。 材料和方法：使用两个总共 553 名健康个体的独立队列，我们采用多元距离矩阵回归 (MDMR) 来确定是否有任何大脑区域表现出与尼安德特人渗入程度显着相关的全脑功能连接模式。然后将识别出的簇用作后续基于种子的功能连接分析中的感兴趣区域，以确定驱动关系的连接模式。结果：MDMR 分析显示，源自尼安德特人的多态性的百分比与顶内沟 (IPS) 区域的功能连接模式显着相关，该区域在两个队列中几乎相同。使用这些 IPS 簇作为基于种子的连接性分析的感兴趣区域，我们再次发现，在两个队列中，具有较高比例的尼安德特人衍生遗传变异的个体表现出 IPS 与视觉处理区域的功能连接性增加，但与社会认知区域的 IPS 连接性降低。 结论：这些发现表明，尼安德特人混合物的残余物继续影响当今人类的大脑功能，其方式与尼安德特人的人类学概念一致表型，包括尼安德特人可能依赖视觉处理能力而牺牲社会认知的可能性，这可能通过减少文化维护和无法应对资源波动而导致该物种的灭绝。这项研究和其他利用有关古代 DNA 的新兴科学的研究提供了一个观察很久以前的古代谱系的窗口。
Aim: To determine whether Neanderthal-derived genetic variation relates to functional connectivity patterns in the brains of living modern humans.Introduction: Nearly 50,000 years ago, Neanderthals interbred with ancestors of modern humans, imparting a genetic legacy that lives on today. The vestiges of this Neanderthal-derived genetic variation have been previously shown to be enriched in genes coding for neurogenesis and myelination and to alter skull shape and brain structure in living people.Materials and Methods: Using two independent cohorts totaling 553 healthy individuals, we employed multivariate distance matrix regression (MDMR) to determine whether any brain areas exhibited whole-brain functional connectivity patterns that significantly related to the degree of Neanderthal introgression. Identified clusters were then used as regions of interest in follow-up seed-based functional connectivity analyses to determine the connectivity patterns driving the relationships.Results: The MDMR analysis revealed that the percentage of Neanderthal-originating polymorphisms was significantly associated with the functional connectivity patterns of an area of the intraparietal sulcus (IPS) that was nearly identical in both cohorts. Using these IPS clusters as regions of interest in seed-based connectivity analyses, we found, again in both cohorts, that individuals with a higher proportion of Neanderthal-derived genetic variation showed increased IPS functional connectivity with visual processing regions, but decreased IPS connectivity with regions underlying social cognition.Conclusions: These findings demonstrate that the remnants of Neanderthal admixture continue to influence human brain function today, in ways that are consistent with anthropological conceptualizations of Neanderthal phenotypes, including the possibility that Neanderthals may have depended upon visual processing capabilities at the expense of social cognition, and this may have contributed to the extinction of this species through reduced cultural maintenance and inability to cope with fluctuating resources. This and other studies capitalizing on the emerging science surrounding ancient DNA provide a window through which to view an ancient lineage long past.