Neanderthal Genomics Suggests a Pleistocene Time Frame for the First Epidemiologic Transition
Charlotte Jane Houldcroft , Simon Underdown
High quality Altai Neanderthal and Denisovan genomes are revealing which regions of archaic hominin DNA have persisted in the modern human genome. A number of these regions are associated with response to infection and immunity, with a suggestion that derived Neanderthal alleles found in modern Europeans and East Asians may be associated with autoimmunity. Independent sources of DNA-based evidence allow a re-evaluation of the nature and timing of the first epidemiologic transition. By combining skeletal, archaeological and genetic evidence we question whether the first epidemiologic transition in Eurasia was as tightly tied to the onset of the Holocene as has previously been assumed. There is clear evidence to suggest that this transition began before the appearance of agriculture and occurred over a timescale of tens of thousands of years. The transfer of pathogens between human species may also have played a role in the extinction of the Neanderthals.
Analysis of whole mitogenomes from ancient samples
Gloria G. Fortes, Johanna L.A. Paijmans
(Submitted on 17 Mar 2015)
Ancient mitochondrial DNA has been used in a wide variety of palaeontological and archaeological studies, ranging from population dynamics of extinct species to patterns of domestication. Most of these studies have traditionally been based on the analysis of short fragments from the mitochondrial control region, analysed using PCR coupled with Sanger sequencing. With the introduction of high-throughput sequencing, as well as new enrichment technologies, the recovery of full mitochondrial genomes (mitogenomes) from ancient specimens has become significantly less complicated. Here we present a protocol to build ancient extracts into Illumina high-throughput sequencing libraries, and subsequent Agilent array-based capture to enrich for the desired mitogenome. Both are based on previously published protocols, with the introduction of several improvements aimed to increase the recovery of short DNA fragments, while keeping the cost and effort requirements low. This protocol was designed for enrichment of mitochondrial DNA in ancient or degraded samples. However, the protocols can be easily adapted for using for building libraries for shotgun-sequencing of whole genomes, or enrichment of other genomic regions.
Eight thousand years of natural selection in Europe
Iain Mathieson , Iosif Lazaridis , Nadin Rohland , Swapan Mallick , Bastien Llamas , Joseph Pickrell , Harald Meller , Manuel A. Rojo Guerra , Johannes Krause , David Anthony , Dorcas Brown , Carles Lalueza Fox , Alan Cooper , Kurt W. Alt , Wolfgang Haak , Nick Patterson , David Reich
The arrival of farming in Europe beginning around 8,500 years ago required adaptation to new environments, pathogens, diets, and social organizations. While evidence of natural selection can be revealed by studying patterns of genetic variation in present-day people, these pattern are only indirect echoes of past events, and provide little information about where and when selection occurred. Ancient DNA makes it possible to examine populations as they were before, during and after adaptation events, and thus to reveal the tempo and mode of selection. Here we report the first genome-wide scan for selection using ancient DNA, based on 83 human samples from Holocene Europe analyzed at over 300,000 positions. We find five genome-wide signals of selection, at loci associated with diet and pigmentation. Surprisingly in light of suggestions of selection on immune traits associated with the advent of agriculture and denser living conditions, we find no strong sweeps associated with immunological phenotypes. We also report a scan for selection for complex traits, and find two signals of selection on height: for short stature in Iberia after the arrival of agriculture, and for tall stature on the Pontic-Caspian steppe earlier than 5,000 years ago. A surprise is that in Scandinavian hunter-gatherers living around 8,000 years ago, there is a high frequency of the derived allele at the EDAR gene that is the strongest known signal of selection in East Asians and that is thought to have arisen in East Asia. These results document the power of ancient DNA to reveal features of past adaptation that could not be understood from analyses of present-day people.
Improving access to endogenous DNA in ancient bones and teeth
Peter de Barros Damgaard , Ashot Margaryan , Hannes Schroeder , Ludovic Orlando , Eske Willerslev , Morten E Allentoft
Poor DNA preservation is the most limiting factor in ancient genomic research. In the vast majority of ancient bones and teeth, endogenous DNA molecules only represent a minor fraction of the whole DNA extract, rendering traditional shot-gun sequencing approaches cost-ineffective for whole-genome characterization. Based on ancient human bone samples from temperate and tropical environments, we show that an initial EDTA-based enzymatic ‘pre-digestion’ of powdered bone increases the proportion of endogenous DNA several fold. By performing the pre-digestion step between 30 min and 6 hours on five bones, we identify the optimal pre-digestion time and document an average increase of 2.7 times in the endogenous DNA fraction after 1 hour of pre-digestion. With longer pre-digestion times, the increase is asymptotic while molecular complexity decreases. We repeated the experiment with n=21 and t=15-30′, and document a significant increase in endogenous DNA content (one-sided paired t-test: p=0.009). We advocate the implementation of a short pre-digestion step as a standard procedure in ancient DNA extractions from bone material. Finally, we demonstrate on 14 ancient teeth that crushed cementum of the roots contains up to 14 times more endogenous DNA than the dentine. Our presented methodological guidelines considerably advance the ability to characterize ancient genomes.