Sequencing and Analysis of Neanderthal Genomic DNA

TLDR

Our knowledge of Neanderthals is limited to a few remains and artifacts, from which we infer their biology, behavior, and relationship to modern humans. The study characterizes Neanderthals by creating a metagenomic library and applying high‑throughput sequencing and analysis. The authors sequenced the library, used autosomal loci to estimate divergence times, and developed a targeted method to recover specific ancient DNA sequences. The analysis uncovered 65,250 bp of Neanderthal DNA, estimated a most recent common ancestor with humans ~706,000 years ago and a population split ~370,000 years ago, found >99.5 % genome identity, and demonstrated that Neanderthal genomics can be advanced through targeted recovery of ancient DNA.

Abstract

Our knowledge of Neanderthals is based on a limited number of remains and artifacts from which we must make inferences about their biology, behavior, and relationship to ourselves. Here, we describe the characterization of these extinct hominids from a new perspective, based on the development of a Neanderthal metagenomic library and its high-throughput sequencing and analysis. Several lines of evidence indicate that the 65,250 base pairs of hominid sequence so far identified in the library are of Neanderthal origin, the strongest being the ascertainment of sequence identities between Neanderthal and chimpanzee at sites where the human genomic sequence is different. These results enabled us to calculate the human-Neanderthal divergence time based on multiple randomly distributed autosomal loci. Our analyses suggest that on average the Neanderthal genomic sequence we obtained and the reference human genome sequence share a most recent common ancestor ∼706,000 years ago, and that the human and Neanderthal ancestral populations split ∼370,000 years ago, before the emergence of anatomically modern humans. Our finding that the Neanderthal and human genomes are at least 99.5% identical led us to develop and successfully implement a targeted method for recovering specific ancient DNA sequences from metagenomic libraries. This initial analysis of the Neanderthal genome advances our understanding of the evolutionary relationship of Homo sapiens and Homo neanderthalensis and signifies the dawn of Neanderthal genomics.