Neanderthal Genomics Suggests a Pleistocene Time Frame for the First Epidemiologic Transition

Charlotte Jane Houldcroft , Simon Underdown
doi: http://dx.doi.org/10.1101/017343

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.

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
doi: http://dx.doi.org/10.1101/014985

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.