NUCLEOTIDE SEQUENCE COMPARISON SERIES

They have provided many opportunities to revisit evolutionary scenarios developed from patterns of cultural variation among archeological sites (e.g., the spread of steppe-related ancestry during the Eneolithic and early Bronze Age, see Allentoft et al., 2015 Haak et al., 2015 Damgaard et al., 2018a Narasimhan et al., 2019 Wang et al., 2019) and from patterns of genetic variation in present-day populations (e.g., the temporal and geographic rise of lactose tolerance in western Eurasia, Mathieson et al., 2015 Ségurel and Bon, 2017).

NUCLEOTIDE SEQUENCE COMPARISON SERIES

Ancient genome time series have made it possible to chart migration, admixture, and selection through space and time at unprecedented resolution. Since then, hundreds of ancient genomes have been characterized across many branches of the tree of life, including humans, horses, dogs, pigs, cattle, goats, wooly mammoths, but also many human pathogens and crops such as maize, sorghum, and barley (see Marciniak and Perry, 2017 and Brunson and Reich, 2019 for reviews). The first genome from an ancient human individual was sequenced in 2010 ( Rasmussen et al., 2010) and was immediately followed by the genome sequencing of a Neanderthal ( Green et al., 2010) and Denisovan ( Reich et al., 2010) individual, two extinct archaic hominins. As the molecular complexity of ancient DNA libraries is generally limited, the mapping strategy recommended here is essential to limit both sequencing costs and sample destruction. Our work contributes to improve the accuracy of DNA methylation maps and to maximize the amount of recoverable genetic information from archeological and subfossil material. It also impacts on ancient DNA methylation estimates as it maximizes coverage improvement within CpG dinucleotide contexts, which hold the vast majority of DNA methylation marks in mammals. This strategy significantly improves the genome coverage especially when DNA templates are shorter than 90 bp, as is typically the case for ancient DNA. We identify a read alignment strategy making use of the Bowtie2 aligner that substantially reduce computational times but shows increased sensitivity relative to previous recommendations based on the BWA aligner. In this study, we use both simulated and real ancient DNA sequence data to benchmark the performance of the read alignment tools most commonly used in ancient DNA research. However, the capacity of different sequence aligners to identify ultrashort and deaminated ancient DNA templates and their impact on the characterization of ancient methylomes remain overlooked. The combination of dedicated statistical techniques and specific molecular tools aimed at reducing the impact of post-mortem DNA damage can also help recover epigenetic data from ancient individuals. 2GLOBE Institute, University of Copenhagen, Copenhagen, DenmarkĪpplying high-throughput DNA sequencing technologies to the ancient DNA molecules preserved in subfossil material can provide genetic information from past individuals, populations, and communities at the genomic scale.1Laboratoire d’Anthropobiologie et d’Imagerie de Synthèse, CNRS UMR 5288, Faculté de Médecine de Purpan, Toulouse, France.Marine Poullet 1 and Ludovic Orlando 1,2*

Nucleotide sequence comparison