Thursday, April 8, 2010

Comparing Neanderthal and modern human DNA

First graph: Distributions of Pairwise Sequence Differences among Humans, the Neanderthal, and Chimpanzees. X axis = number of sequence differences; Y axis = percent of pairwise comparisons. (Krings et al, 1997).

Second graph: Green: human/human comparisons; Red: human/Neanderthal comparisons; Blue: human/chimp comparisons. X axis = number of sequence differences; Y axis = fraction of pairwise comparisons. (Green et al. 2008)

Did the Neanderthal gene pool overlap with the modern human gene pool? In other words, are some modern humans genetically closer to some Neanderthals than they are to other modern humans?

The answer is ‘yes’ if we look at individual DNA sequences, as shown in the first graph (above):

Thus, the largest difference observed between any two human sequences was two substitutions larger than the smallest difference between a human and the Neandertal. In total, 0.002% of the pairwise comparisons between human mtDNA sequences were larger than the smallest difference between the Neandertal and a human (Krings et al., 1997)

It may be noted that a small fraction (0.037%) of the inter-human comparisons are larger than the smallest distance (29 substitutions) between the Neandertal and humans. (Krings et al., 1999)

We see the same genetic overlap among present-day human populations. Some Danes seem to be closer to some Congolese than to other Danes. But this overlap disappears when we compare more than one DNA sequence at the same time. The more sequences we compare simultaneously, the less overlap there is (Risch et al., 2002; Sesardic, 2010).

We can likewise eliminate the overlap between Neanderthals and modern humans if we use the entire mtDNA genome to compare these two populations:

In 2008, the first complete sequencing of Neandertal mtDNA was announced (Green et al. 2008). A complete mtDNA genome of 16,565 base pairs was extracted from a 38,000 year old fossil from the Vindija cave in Croatia. As Krings et al. 2007 had done, the authors created a graph showing the numbers of base pair differences for humans, chimps and the Neandertal when compared against humans. Because they were able to compare across the whole genome rather than a small portion of it, the differences between humans and the Neandertal was far more striking (Fossil Hominids)

This may be seen in the second graph (above).

But why must we compare entire genomes to make the overlap go away? Why should there be any genetic overlap between two populations for any stretch of DNA if the same populations show absolutely no visual overlap to our lying eyes? What’s going on here?

The underlying reason is that most of the genome has little selective value. So the selection pressure on that DNA is pretty much the same in any population, be it Congolese, Danish, or Neanderthal. Of course, once two populations become reproductively isolated, i.e., when they become different species, their DNA will start to drift apart even at genes of low selective value (because of differing patterns of random mutations). But this divergence is very slow. Consequently, it is hard to distinguish between related species that have diverged from each other only over the last 40,000 years. This is why Neanderthals and modern humans still have some overlap, even though their last common ancestor lived over 400,000 years ago.


Fossil Hominids: mitochondrial DNA,

Green, R., A-S. Malaspinas, J. Krause, A. Briggs, et al. (2008). A complete Neandertal mitochondrial genome sequence determined by high-throughput sequencing, Cell, 134, 416-426.

Krings, M., H. Geisert, R.W. Schmitz, H. Krainitzki, & S. Pääbo. (1999). DNA sequence of the mitochondrial hypervariable region II from the Neandertal type specimen, Proc. Nat. Acad. Sci. USA, 96, 5581-5585.

Krings, M., A. Stone, R.W. Schmitz, H. Krainitzki, M. Stoneking, & S. Pääbo. (1997). Neandertal DNA sequences and the origin of modern humans, Cell, 90, 19-30.

Risch, N., E. Burchard, E. Ziv, & H. Tang. (2002). Categorization of humans in biomedical research: genes, race and disease, Genome Biol, 3, 1-12.

Sesardic, N. (2010). Race: a social destruction of a biological concept, Biol. Philos, 25, 143-162.


Tod said...

The lying reconstructions make Neanderthals look like sturdy broad faced versions of modern Europeans. People accept the evidence of their eyes and conclude we are somehow related. An accurate reconstruction is long overdue, that will need a acknowledged expert on Neanderthals who is prepared to make his subject less appealing. Don't hold your breath.

Doesn't a negative mitochondrial DNA comparison leave open the question of a Neanderthal male mating with a modern human female?

I think the most likely way that could have happened would be an infant Neanderthal being kept as a pet after it's parents had been hunted. Bearing in mind how fast they matured after several years it could concievably have impregnated a modern human female.

If your hypothesis is right the differences in appearance between Europeans and Africans are the result of selection for appearance in Europeans. If people assume the the visual differences are simple reflections of function they may overestimate the actual difference between Danes and Congolese.

For an analogy, a car can have sportscar styling which makes people assume it goes very fast even though it might not have any more speed or be more aerodynamic than a family car.

Peter Frost said...


Most of the non-overlapping differences among human populations are literally 'skin-deep.' Differences in body tissues and body chemistry tend to be less pronounced and more statistical.

What I find strange is that most people consider 'skin-deep' differences to be trifling and unimportant. This may be a legacy of our Christian heritage with its body/soul dichotomy.

In theory, once we have the Neanderthal genome fully sequenced, we should be able to reconstruct the actual physical appearance of a Neanderthal. In theory. Unfortunately, we don't really understand how a genome works. I don't believe we'll be able to make a baby Neanderthal (à la Jurassic Park), but we should be able to create specific body tissues (e.g., skin, hair). There's research work going on now to grow skin grafts from individual human cells.

Traditionally, species have been defined as populations that cannot interbreed and produce fertile offspring. Yet there seem to be an awful lot of exceptions to this rule. When I mention this point to zoologists, they usually smile and reply that the line between a 'species' and a 'subspecies' is arbitrary.