Person:

Lipson, Mark

The human mutation rate is an essential parameter for studying the evolution of our species, interpreting present-day genetic variation, and understanding the incidence of genetic disease. Nevertheless, our current estimates of the rate are uncertain. Most notably, recent approaches based on counting de novo mutations in family pedigrees have yielded significantly smaller values than classical methods based on sequence divergence. Here, we propose a new method that uses the fine-scale human recombination map to calibrate the rate of accumulation of mutations. By comparing local heterozygosity levels in diploid genomes to the genetic distance scale over which these levels change, we are able to estimate a long-term mutation rate averaged over hundreds or thousands of generations. We infer a rate of 1.61 ± 0.13 × 10−8 mutations per base per generation, which falls in between phylogenetic and pedigree-based estimates, and we suggest possible mechanisms to reconcile our estimate with previous studies. Our results support intermediate-age divergences among human populations and between humans and other great apes.

Ancient DNA studies have established that Neolithic European populations were descended from Anatolian migrants1–8 who received a limited amount of admixture from resident hunter-gatherers3–5,9. Many open questions remain, however, about the spatial and temporal dynamics of population interactions and admixture during the Neolithic period. Using the highest-resolution genome-wide ancient DNA data set assembled to date—a total of 180 samples, 130 newly reported here, from the Neolithic and Chalcolithic of Hungary (6000–2900 BCE, n = 100), Germany (5500–3000 BCE, n = 42), and Spain (5500–2200 BCE, n = 38)—we investigate the population dynamics of Neolithization across Europe. We find that genetic diversity was shaped predominantly by local processes, with varied sources and proportions of hunter-gatherer ancestry among the three regions and through time. Admixture between groups with different ancestry profiles was pervasive and resulted in observable population transformation across almost all cultural transitions. Our results shed new light on the ways that gene flow reshaped European populations throughout the Neolithic period and demonstrate the potential of time-series-based sampling and modeling approaches to elucidate multiple dimensions of historical population interactions.

We report the Simons Genome Diversity Project (SGDP) dataset: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioral modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that in other non-Africans.

We generated genome-wide DNA data from four children buried roughly 8000 and 3000 years ago at Shum Laka (Cameroon), one of the earliest archaeological sites within the probable homeland of Bantu languages. One individual carried the deeply divergent Y chromosome haplogroup A00, which is found today almost exclusively in the same region. However, all four individuals’ genome-wide ancestry profiles are most similar to West-Central African hunter-gatherers, implying that present-day populations in western Cameroon, as well as Bantu speakers across the continent, are not descended substantially from the population represented by these four people. We infer an Africa-wide phylogeny that features widespread admixture and three prominent radiations, including one giving rise to at least four major lineages deep in the history of modern humans.

Humans settled the Caribbean ~6,000 years ago, with ceramic use and intensified agriculture marking a shift from the Archaic to the Ceramic Age ~2,500 years ago. We report genome-wide data from 174 individuals from The Bahamas, Hispaniola, Puerto Rico, Curaçao, and Venezuela co-analyzed with published data. Archaic Age Caribbean people derive from a deeply divergent population closest to Central and northern South Americans; contrary to previous work, we find no support for ancestry contributed by a population related to North Americans. Archaic lineages were >98% replaced by a genetically homogeneous ceramic-using population related to Arawak-speakers from northeast South America who moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools reflecting small effective population sizes which we estimate to be a minimum of Ne=500-1500 and a maximum of Ne=1530-8150 on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the analyzed individuals lived. Census sizes are unlikely to be more than ten-fold larger than effective population sizes, so previous estimates of hundreds of thousands of people are too large. Confirming a small, interconnected Ceramic Age population, we detect 19 pairs of cross-island cousins, close relatives ~75 kilometers apart in Hispaniola, and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically-differentiated groups from the mainland but instead reflected interactions within an interconnected Caribbean world.

Abstract A major topic of interest in human prehistory is how the large-scale genetic structure of modern populations outside of Africa was established. Demographic models have been developed that capture the relationships among small numbers of populations or within particular geographical regions, but constructing a phylogenetic tree with gene flow events for a wide diversity of non-Africans remains a difficult problem. Here, we report a model that provides a good statistical fit to allele-frequency correlation patterns among East Asians, Australasians, Native Americans, and ancient western and northern Eurasians, together with archaic human groups. The model features a primary eastern/western bifurcation dating to at least 45,000 years ago, with Australasians nested inside the eastern clade, and a parsimonious set of admixture events. While our results still represent a simplified picture, they provide a useful summary of deep Eurasian population history that can serve as a null model for future studies and a baseline for further discoveries.