Population genomic methodology for analysis of ancient DNA: assessing population relationships and the temporal dynamics of natural selection

项目概要 现在有数百个来自包括人类在内的各种物种的古代基因组。这样的 数据提供了了解近代人口学和自然选择历史的直接窗口，并且 极大地促进了对人类走出非洲后如何殖民世界的理解 分散。尽管如此，分析古代DNA的统计方法仍然落后于现代科学技术。 测序技术的发展。拟议的研究将开发基于以下内容的新方法 群体基因组学理论推动了古代 DNA 研究领域的发展。这些方法将应用于 来自古代人类的数据为过去 5 万年的人类进化提供了新的见解。 此外，通过与国际古DNA实验室的合作，这些方法的应用将 有助于理解动物驯化，这是人类形成的一项关键创新 复杂的社会。我们将开发统计方法来评估古代样本与 当今的个体以一种明确解释等位基因作为新突变出现并且是 因此在古代样本中频率较低。通过与研究猪驯化的合作者合作，我们将 检验有关人类移动如何与农业和人类文明的出现同时发生的假设 家养动物的运输。我们还将开发方法来阐明现代技术的细节 人类和远古人类，例如尼安德特人，进行了杂交。通过利用尼安德特人的变异模式 欧亚人群内部和人群之间的 DNA 共享，我们将确定人类和 尼安德特人杂交，决定了泛大陆尼安德特人的人口结构。 最后，我们将利用古代 DNA 来加深我们对马驯化过程中自然选择的理解 以及人类的驱散。我们将与国际合作者合作，利用古代 DNA 来检测基因 对马驯化至关重要，并确定突变是否在驯化之前存在或是否存在 它们在驯化后重新出现。我们还将研究健身效果的分布如何 通过比较古代推断的健身效果的分布，了解人类随时间和空间的变化 不同年龄的样本，以便了解人类的适应是如何形成的 过去十万年的人口历史和气候变化。

Project Summary There are now hundreds of ancient genomes available from a wide range of species, including humans. Such data provide a direct window into the history of demography and natural selection in the recent past, and have greatly contributed to the understanding of how humans colonized the world following the out-of-Africa dispersal. Nonetheless, the statistical methods for analyzing ancient DNA have lagged behind the developments in sequencing technology. The proposed research will develop novel methods based on population genomics theory to advance the field of ancient DNA research. These methods will be applied to data from ancient humans to provide new insights into the last 50 thousand years of human evolution. Moreover, via collaboration with international ancient DNA laboratories, applications of these methods will contribute to the understanding of animal domestication, a key innovation that allowed humans to form complex societies. We will develop statistical methods to assess the relationship of ancient samples to present-day individuals in a way that explicitly accounts for the fact that alleles arose as new mutations and are thus at lower frequency in ancient samples. By working with collaborators studying pig domestication, we will test hypotheses about how movement of humans coincided with the advent of agriculture and the transportation of domesticated animals. We will also develop methodology to elucidate details of how modern humans and archaic humans, such as Neandertals interbred. By leveraging patterns of variation in Neandertal DNA sharing within and among Eurasian populations, we will determine the number of times that humans and Neandertals interbred, and determine demographic structure in the pan-continental Neandertal population. Finally, we will use ancient DNA to refine our understanding of natural selection during horse domestication and human dispersal. Working with international collaborators, we will use ancient DNA to detect genes that were critical to horse domestication, and determine whether the mutations existed before domestication or if they arose de novo following domestication. We will also examine how the distribution of fitness effects has changed over time and space in humans by comparing the distribution of fitness effects inferred for ancient samples of varying ages, in order to gain an understanding of how human adaptation has been shaped by demographic history and climate change over the last hundred thousand years.