An ancestral recombination graph of human, Neanderthal, and Denisovan genomes

Abstract

Many humans carry genes from Neanderthals, a legacy of past admixture. Existing methods detect this archaic hominin ancestry within human genomes using patterns of linkage disequilibrium or direct comparison to Neanderthal genomes. Each of these methods is limited in sensitivity and scalability. We describe a new ancestral recombination graph inference algorithm that scales to large genome-wide datasets and demonstrate its accuracy on real and simulated data. We then generate a genome-wide ancestral recombination graph including human and archaic hominin genomes. From this, we generate a map within human genomes of archaic ancestry and of genomic regions not shared with archaic hominins either by admixture or incomplete lineage sorting. We find that only 1.5 to 7% of the modern human genome is uniquely human. We also find evidence of multiple bursts of adaptive changes specific to modern humans within the past 600,000 years involving genes related to brain development and function.

Temporal mapping of derived high-frequency gene variants supports the mosaic nature of the evolution of Homo sapiens

“…Our analysis shows a bimodal distribution of the age of modern human-derived high-frequency variants (in consonance with the findings of 54 on a more limited set of variants ). The two peaks likely reflect, on the one hand, the point of divergence between Homo sapiens and other Homo species and, on the other, the period of population dispersal and replacement following the last major out of Africa event.…”

Efficient ancestry and mutation simulation with msprime 1.0

“…The succinct tree sequence data structure developed for provides a view of not only genetic variation, but also the genetic ancestry that produced that variation. Recent breakthroughs in methods to infer genetic ancestry in recombining organisms ( Rasmussen et al 2014 ; Kelleher et al 2019 ; Speidel et al 2019 , 2021 ; Schaefer et al 2021 ; Wohns et al 2021 ) have made it possible to estimate such ancestry from real data at scale for the first time ( Harris 2019 ; Tang 2019 ). Given such inferred ancestry, many exciting applications become possible.…”

A unified genealogy of modern and ancient genomes

“…The methods described here produce high-quality dated genealogies that include thousands of modern and ancient samples. These genealogies cannot be entirely accurate; nevertheless, they enable a wealth of analyses that reveal features of human evolution (23,(56)(57)(58)(59)(60). That our highly simplistic geographic estimator captures key events suggests that more-sophisticated approaches, coupled with the ongoing program of sequencing ancient samples, will continue to generate insights into our history.…”