Relationship of Neanderthals to Modern Humans After extracting ancient DNA from the 40,000-year-old bones of Neanderthals, scientists have obtained a draft sequence of the Neanderthal genome, yielding important new insights into the evolution of modern humans. No other ancient people have aroused more controversy and confusion over the last century and a half than have the Neanderthals (3,4). There is an on-going debate as to whether they should be considered Homo sapiens.
While the idea that modern humans originated in Africa and spread out to other parts of the world is widely accepted, several scenarios have been proposed to account for the replacement of neanderthal populations. The multi regional hypothesis holds that neanderthal populations in Eurasia and Africa were held together by gene flow. Fossil and genetic evidence supports an African origin for Modern Humans (1,3,5,9,10).
A decade after scientists first cracked the human genome, researchers announced that they have done the same for Neanderthals, the species of hominid that existed from roughly 400,000 to 30,000 years ago, when their closest relatives, early modern humans, may have driven them to extinction (1,3,5,9,10). Led by ancient-DNA expert Svante Paabo of Germany’s Max Planck Institute for Evolutionary Anthropology, scientists reconstructed about 60% of the Neanderthal genome by analyzing tiny chains of ancient DNA extracted from bone fragments of three female Neanderthals excavated in the late 1970s and early ’80s from a cave in Croatia (6,8).
The bones are 38,000 to 44,000 years old. The genetic information turned up some intriguing findings, indicating, for instance, that at some point after early modern humans migrated out of Africa, they mingled and mated with Neanderthals, possibly in the Middle East or North Africa as much as 80,000 years ago (5,7,10). If that is the case, it occurred significantly earlier than scientists who support the interbreeding hypothesis would have expected. Comparisons with DNA from modern humans show that some Neanderthal DNA has survived to the present (3,4,7).
Moreover, by analyzing ancient DNA alongside modern samples, scientists were able to identify a handful of genetic changes that evolved in modern humans sometime after their ancestors and Neanderthals diverged, 440,000 to 270,000 years ago (2,4). Researchers compared the Neanderthal genome with the genomes of five living people: one San from southern Africa, one Yoruba from West Africa, one Papua New Guinean, one Han Chinese and one French person (2,4,6).
Scientists discovered that 1% to 4% of the latter three DNA samples is shared with Neanderthals — proof that Neanderthals and early modern humans interbred. The absence of Neanderthal DNA in the genomes of the two present-day Africans indicates that interbreeding occurred after some root population of early modern humans left Africa but before the species evolved into distinct groups in Europe and Asia (1,3,5,9,10). All studies of Neanderthal genomic DNA use material obtained from fossilized Neanderthal bones that are tens of thousands of years old.
As one might expect, the quality of the material that can be recovered from such specimens is very poor, as DNA degrades over time. Consequently, there is wide variability in DNA preservation among available Neanderthal specimens, and most Neanderthal bones yield no usable DNA (2,3,4). When present, Neanderthal genomic DNA is recovered in short (50- to 100-bp) fragments (2,3,4) The information content of Neanderthal DNA is also degraded: Individual nucleotides are subject to chemical modification, with deamination of cytosine to uracil the most common lesion (2,4).
Moreover, the fragments of Neanderthal genomic DNA are mixed with microbial contaminants that constitute >90% of the recovered DNA. The amount of DNA damage and microbial contamination are dependent on ambient environmental conditions: The ancient specimens that have provided the most intact DNA are mammoth remains recovered from permafrost. These specimens often include preserved hair shafts and soft tissues from which relatively high-quality DNA can be recovered (2,4,5).
None of the Neanderthal specimens providing the DNA for whole-genome sequencing approach this level of preservation (2,4,5,6). In addition to these challenges, ancient specimens frequently become contaminated with modern human DNA during handling and DNA extraction (2). This poses obvious problems for distinguishing modern human from Neanderthal DNA, since the frequency of single-base mismatches between the two genomes is estimated to be
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