基于祖先重组图重建古今人类群体遗传系谱的研究进展及展望

Advancements and prospects in reconstructing the genetic genealogies of ancient and modern human populations using ancestral recombination graphs

随着古今人群大规模基因组资源的公布、计算生物学工具的革新及大数据挖掘相关算力的提升,基因组学领域正在经历一场革命性的变化。这些进步和变化不仅显著加深了人们对人类起源、迁徙及混合等复杂演化历程的理解,而且也揭示了这些过程对人类疾病健康状态的影响,加速了人们对人类健康和疾病遗传学基础的研究,还为挖掘人类基因组中记载的群体演化历史及疾病遗传学基础的演化轨迹提供了新的途径。祖先重组图(ancestral recombination graph,ARG)技术,通过分析全基因组中不同区域的重组事件和共祖特征,重建了基因组片段之间的演化关系。ARG记录了所研究基因组序列分歧以来的所有共祖和重组事件,并指明了每个基因组位置的完整系谱,是基因组分析的理想数据结构。本文综述了ARG技术的理论基础及其研究进展,并探讨了其在法医基因组学、群体遗传学、演化医学、医学基因组学等多个学科领域的转化应用和发展前景,以期推动该技术在基因组学研究中的应用,进一步深化对人类基因组的理解。

With the release of large-scale genomic resources from ancient and modern populations,advancements in computational biology tools,and the enhancement of data mining capabilities,the field of genomics is undergoing a revolutionary transformation.These advancements and changes have not only significantly deepened our understanding of the complex evolutionary processes of human origins,migration,and admixture but have also unveiled the impact of these processes on human health and disease.They have accelerated research into the genetic basis of human health and disease and provided new avenues for uncovering the evolutionary trajectories recorded in the human genome related to population history and disease genetics.The ancestral recombination graph(ARG)reconstructs the evolutionary relationships between genomic segments by analyzing recombination events and coalescence patterns across different regions of the genome.An ARG provides a record of all coalescence and recombination events since the divergence of the sequences under study and specifies a complete genealogy at each genomic position,which is the ideal data structure for genomic analysis.Here,we review the theoretical foundations and research advancements of the ARG,and explore its translational applications and future prospects across various disciplines,including forensic genomics,population genetics,evolutionary medicine,and medical genomics.Our goal is to promote the application of this technique in genomic research,thereby deepening our understanding of the human genome.