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What Genomics Says About Being Human Part II

By David Micklos
DNA Learning Center (DNALC), Cold Spring Harbor Laboratory

DNA sample

In the first article in this series, I discussed how our genome has changed in the 6 million years since we diverged from a common ancestor with chimpanzees, and how students can include their own mitochondrial DNA sequence in a study to show that all humans alive today share a common ancestor who lived about 150,000 years ago in Africa. In this article, I will explore what the analysis of ancient DNA says about us and our nearest relative. This has been made possible by the perfection of methods to amplify and assemble nucleotide sequences from the small amount of DNA that is preserved in bones dating back as far as 60,000 years.

Since their discovery in Germany’s Neander Valley in 1856, the heavyset bones of Neanderthal have fascinated scientists, as well as the general public. Neanderthal ranged throughout Europe, the Middle East, and western Russia beginning about 300,000 years ago and became extinct about 30,000 years ago. With mostly the same anatomical features as Homo sapiens, including a larger average brain volume, Neanderthal was our closest hominid relative. However, illustrations and museum reconstructions traditionally cast Neanderthal as a lumbering brute. A primitive tool set and scant evidence of ceremonial burials completed the impression of Neanderthal as different from Homo sapiens (thinking man).

The fact that Neanderthal shared the same geographical range with modern humans for at least 10,000 years raises a number of questions. What is our genetic relationship to Neanderthal? Was Neanderthal the ancestor of modern Europeans? Did he interbreed with our ancestors? Recent analysis of the Neanderthal genome has provided definitive answers to these questions and recast Neanderthal in a different light.

A 1997 analysis of a sequence from the Neanderthal mitochondrial genome conclusively showed that modern humans are not directly descended from Neanderthal, but that we shared a common ancestor about 600,000 years ago. However, because the mitochondrial genome is inherited only through a female lineage, this analysis was mute on whether or not our ancestors interbred with Neanderthal. The answer to that question had to await the publication, in May 2010, of the draft sequence of the Neanderthal nuclear genome.

The Neanderthal and chimpanzee genomes and genomes of contemporary humans were compared to identify “fixed” nucleotide substitutions—locations where all humans share the same nucleotide but where Neanderthal and chimp share a different (ancestral) nucleotide. This genome-wide analysis turned up only 78 nucleotide substitutions that cause amino acid differences in proteins between humans and Neanderthal. Pair-wise comparison of single nucleotide polymorphisms (SNPs) between Neanderthal and contemporary humans showed a significantly greater number of matches with Europeans and Asians than with Africans.

Neanderthal matched long-range SNP patterns (haplotypes) in 10 of 12 Asian and European chromosome regions showing high SNP diversity. This provided strong evidence that Neanderthal contributed 1 to 4% of the DNA of modern Europeans and Asians. The “gene flow” from Neanderthal into the human genome likely occurred 50,000 to 80,000 years ago in the Middle East, after modern humans migrated out of Africa but prior to their dispersion into Europe and Asia.

Detailed analysis of individual genes paints a picture of a decidedly “modern” Neanderthal. Some Neanderthal individuals have a point mutation in the gene for the melanocorticoid ligand receptor (mclr) that regulates skin and hair pigmentation. This mutation is biologically equivalent to mclr mutations that produce the characteristic “ Irish” phenotype of fair skin and red hair. Fair-skinned Neanderthals would have absorbed more UVB light needed to synthesize vitamin D, an advantage during winter months at higher latitudes.

Neanderthal also shares with contemporary humans a key mutation of the TAS2R38 receptor on the tongue that diminishes perception of bitter taste. This may have freed hominids to include more bitter-tasting plants in their diet, as opposed to avoiding them. Neanderthal also shares with every human 2 amino acid changes in the FOXP2 protein, which appear crucial to articulate speech. Still, it is impossible to tell if Neanderthal had language or even when this ability developed in humans.

During most of the vast span of evolution, including intermixing with Neanderthal, Homo sapiens subsisted entirely by hunting and gathering. The domestication of plants was perhaps the single greatest civilizing factor in human history. The increased productivity of cereal crops made it possible for fewer and fewer farmers to produce enough food for growing numbers of non-farmers—artisans, engineers, teachers, administrators, and merchants—freeing them to develop other elements of culture.

Luca Cavalli-Sforza first described this “Neolithic transition” from hunter-gatherers to farmers in genetic terms, when he identified an east-west gradient in the allele frequencies of blood proteins. This appeared to mirror the spread of agriculture across Europe, beginning about 10,000 years ago and progressing at a rate of about 1 km per year from the site of wheat and barley domestication in southeastern Turkey.

A cemetery that served an ancient farming community was discovered in Derenburg, central Germany. Recent DNA analysis of human remains found in the cemetery provides strong support for Cavalli-Sforza’s demic diffusion model, in which waves of Neolithic farmers mixed their genes with indigenous hunter-gatherers as they spread across Europe in search of new fields. (Demic refers to a deme, a local population of a species.)

Mitochondrial SNPs from 22 skeletons in the cemetery dated to 7,100 years ago were compared with SNPs from contemporary European populations. The strongest associations were with modern populations from central Europe, as well as from Turkey, Syria, and Iraq. This is the genetic signature one would expect of agriculturalists arriving from the Middle East and mixing with, but not completely replacing, local hunter-gatherer populations.

It is obvious that the evolution of Homo sapiens’ superior brain provided a competitive advantage over other creatures. However, the cemetery at Derenburg provides evidence that the human-directed evolution of plants— agriculture—provided an adaptive advantage that allowed farmers, and their genes, to gain ascendancy over their hunter-gatherer forebears.

Note: This series of articles is excerpted from Genome Science, to be published later this year by the Cold Spring Harbor Laboratory Press. It will be available for purchase at Carolina.com.—Ed.

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