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

Abstract

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.