Cavemen in Your Genes

The familiar nursery rhyme (…What are little boys made of? Frogs and snails and puppy-dogs’ tails…) has more merit than many of us realize. Indeed, mother nature is the eldest and most accomplished genetic engineer among us. In the next posts I’m going to highlight the unexpected ways in which we have been patched together over the last couple of billion years to arrive at the chimaera that we call human.

Blending Via Sex

We’re all a blend of our ancestors. Some of it is quite a straightforward process: being diploid, your paired chromosomes are the sum of half of your father’s set and half of your mother’s. Each of their genetic complement is, in turn, a union of their own mothers and fathers, each of whom acquired their genes from two parents before them, and so on and so forth. Therefore, your own genetic material is really a hodge-podge of an ever widening ancestral pool the further back you look. This is the result of genetic blending via sex. Sexual blending is fun, but relatively intuitive.

Kinky Twists

Now things get twisted. Until recently, sex was the only major source of genetic blending known to be going on, but the world has recently begun to look a lot more interesting with the advent of genetic sequencing. Scientists can now peer into the genome (full DNA blueprint) of an individual and read the sequences of nucleotide bases (the units of the DNA molecule, like links in a chain) that compose the genes. And guess what? We are not who we thought we are.

Although there is some variation in the gene sequences of different individuals of a species, each species has characteristic sequence codes in certain genes that set it apart from other species. These sequences slowly change over many generations as mutations accumulate at a slow clocklike rhythm (providing an “evolutionary clock”) that records the evolutionary route that species took as they diverged from each other. Biologists have amassed extensive databases of these characteristic gene sequences against which to compare newly discovered creatures and to determine where they fit into the evolutionary tree of life. The genetic “evolutionary clock” even allows us to estimate the time that has elapsed since two species shared a common ancestor. Such measurements support the fossil record by indicating that chimpanzees and humans diverged around 6 million years ago [1]. Sometimes not only a single gene but the entire DNA sequence of an organism is read and catalogued, yielding invaluable information about the physiology as well as the evolutionary history of an organism.

From these studies came a huge surprise: characteristic gene sequences of one species are often found spliced into the genome of completely unrelated species, including us. Ponder this fact for a moment: our DNA is not completely our own. Some of it (about 1 to 4 percent) is Neanderthal [2], more (8%) is viral [3], and we even have colonies of highly evolved decendents of bacteria living in each of our cells [4].

How can this shuffling have happened? Hold on to that image of promiscuity that may be forming in your mind, for we’ll need to build on it substantially. Fascinating new discoveries are shedding light on the ancient ghosts that haunt the dark corners of our chimaeric genetic identity. What I find most exciting about these discoveries is that they give us a peek into the engine of evolution, bringing us several steps closer to understanding the complex mechanisms by which it works. Together, they weave a remarkable tapestry of the interplay between scientific discovery and the techniques used to make those discoveries.

The Loopy Tree of Life

The evolutionary or phylogenetic ‘tree of life’, which represents how life forms are related to each other, is commonly roughly thought of as a repeatedly branching bush, with a common ancestor at the base and all living or extinct species at the tips of the twigs. It’s a geneology of genetic material. However, research increasingly suggests that this evolutionary tree should be thought of more as a net, with not only branching but also fusing.

Phylogenetic tree of life. You are at about position 11:30, between the rat (Rattus) and the chimpanzee (Pan). (Image: Ivica Letunic)

Over time, the single twig of a species may branch as two populations diverge from each other genetically, forming two new twigs — two new species that are reproductively isolated from each other. Usually, simple geographic separation (via a river, a highway, etc.) is enough to set two populations of a species on different roads. Once they are separated (and remain so for a long time), the evolutionary clock kicks in and mutations accumulate in slightly different ways in each population. Since there is no blending by interbreeding, a big difference in mutations eventually builds up in each population. The precise mechanism of achieving reproductive isolation is not completely understood, but eventually the genes of each population differ by enough mutations that their members cannot produce viable young if they were crossed (either sperm and egg are not compatible, or the two sets of chromosomes do not align properly, or something else), or if their young survive, they are sterile. At this point, the two populations have become different species. This is the commonly understood process of speciation, the generation of new species.

The world is not black and white though, and there is rarely a point at which the two populations suddenly don different species’ jerseys (though exceptions exist, such as genome duplication in plants, but I’ll cover these later). Geographic separation often needs to continue for a long time before enough mutations have accumulated to render the two populations biochemically unable to interbreed. By the time this is achieved, the two species may look substantially different (for example, due to different environments exerting different forces of natural selection on each population). We may easily assign them to different species based on their looks alone, but their populations may still be able to interbreed.

A good example of this flexibility in appearance (called ‘phenotypic plasticity’) is dogs. Chihuahuas and Irish wolfhounds are genetically still the same species. Dog breeding has only been practiced for a short time compared to the evolution of, say, wolves and coyotes. Dogs have been under extremely intense selection pressure during that time, and even though strong selection pressure can generate huge visual differences, there has been insufficient time for the slow march of mutations in the right places to actually prevent eggs and sperm from becoming biochemically incompatible.

A dog with the results of genetic blending: puppies. (image: Stephan Gillmeier)

Sometimes even truly separate species, with genetic incompatibility, will occasionally produce viable young when crossed. Domestic dogs can sometimes successfully breed with wolves and produce puppies. In fact, this phenomenon is one of the dangers currently facing polar bears. Polar bears (Ursus maritimus) are an ice age adapted animal, and they originally descended from brown bears (Ursus arctos) under selection pressure for white coats to hide them from their prey (they have other interesting adaptations, but that’s the most visually obvious one). It was recently found that the most recent matriline (geneology of mothers) of polar bears arose around 20,000 to 50,000 years ago in Ireland, during the last ice age [5]. The polar climate helped to keep them physically separated from brown bears even after the glaciers of the Wisconsian ice age retreated, but global warming now threatens to force them further south, where they may encounter brown bears again. It turns out that polar bears and brown bears can produce viable offspring frequently enough that the intermixing of their populations would lead to genetic blending that could wipe out the distinct white polar bear by homogenization.

So polar bears and brown bears are an example of two twigs of the evolutionary tree of life likely coming together again and fusing into a single branch, forming a kind of loop of genetic material over time, first separating and then rejoining. The tree of life is loopy. (In fact, due to horizontal gene transfer and endosymbiosis, it’s a lot more loopy than you’d think, but I’ll cover those topics further in a subsequent post.)

Phylogenetic tree of life showing both divergence (branching) and horizontal gene transfer (fusion of branches). (Image: Barth F. Smets, Ph.D.)

How Cavemen Got into Your Genes

Enter the human lineage. Our particular branch of the tree of life, the genus Homo, has a fascinating prehistory, especially as it pertains to globetrotting. The fossil evidence of our evolutionary history has really grown a lot in the last few decades, and there are now hundreds of specimens. (It’s unfortunate that creationist proponents who reject the idea of our evolution from other apes continue to focus on the relative dearth of the human fossils that existed during much of the last century. As a result, they have not kept up with recent research and continually report terrible underestimates of the volume of fossils; I’ll cover this issue in a later post.)

Australopithecus africanus reconstruction. (Sculpture by Toni Wirts)

Genus Homo descended from the African Australopithecus around 2.5 million year ago. As early as 1.9 million years ago, Homo erectus left Africa, traveling as far as Java and China (and probably evolving into Homo floresiensis — popularly known as ‘the hobbit’ — in Indonesia, which survived until maybe only 13,000 years ago). This was the first human exodus from Africa.

Human evolution and migration patterns. (Image: Reed DL, Smith VS, Hammond SL, Rogers AR, Clayton DH; 2004)

Then, around half a million years ago, one population of Homo heidelbergensis, a descendent of H. erectus, left Africa again and spread over Europe, eventually giving rise to Homo neanderthalensis, better known as the Neanderthals. This was the second major wave of migration. Meanwhile, our direct ancestors, likely another population of H. heidelbergensis, remained in Africa, with Homo sapiens arriving on the scene around 200,000 years ago.

History from here somewhat mirrors the brown bear/polar bear story. Like the polar bear, Neanderthals may have been an ice age adapted species, living through four glacial maxima (ice ages) as the global climate swung from warm interglacial times to the bitterly cold deep freeze of glatiation in the sequence of stages known as the Pre-Illinoian, Illinoan, Sangamonian and Wisconsin. Even between glaciation events, they remained an exclusively northern species of human, and none of their remains have been found in Africa.

Finally, between 50,000 and 100,000 years ago, a harsh climatic shift in Africa appears to have stimulated the egress of our species from the continent after nearly wiping us out (H. sapiens may have dwindled to under 1000 individuals). This was the third and last major migration of Homo out of Africa. There may have been additional exoduses from Africa involving other human species, but we know that there was a minimum of three excursions.

It must have been a weird time to be alive, 30 to 50 millenia ago. It was one of the few times in history when the planet was home to more than one directly interacting species of human at a time. Archaeological evidence indicates that H. sapiens and H. neanderthalensis met in Europe. The tone of those meetings is not terribly clear, but the rapid demise of Neanderthals upon the invasion of our species (they were gone by 24-40 millenia ago) implies that competition was quite severe [7]. However, until recently, it was unknown what was the answer to the obvious question: with so much interaction, was any flirting taking place?

The advent of genetic sequencing has begun to provide a fascinating positive answer to that question. For the first time, scientists are not limited to infering the depth of interactions by archaeology alone. Molecular biologists sequenced the entire genome (about 3 billion base pairs of DNA) of three Neanderthal individuals found in Vindija Cave in Croatia [9, 10, 11]. Such an analysis is so far only possible for relatively young fossils (this one was about 40,000 years old), because DNA is a relatively fragile molecule and probably would not survive fossilization over millions of years. An initial comparison with the DNA of living humans suggested that up to 2% of the genome of non-Africans was contributed by Neanderthals, probably via interbreeding about 60,000 years ago.

A more recent study by Yotova and others [2] has expanded on these results by mapping the distribution among modern humans of genes with versions that are strongly suspected to be Neanderthal in origin. What Yotova’s team has done is demonstrate the exchange of genetic material between the migrants among our ancestors and Neanderthals. Their research revealed that a small section of the human X-chromosome (the female sex determining chromosome, of which women have two copies and men have one) appears to have come from Neanderthals. Certain genes, such as the dystrophin gene (which codes for an essential protein needed for proper connectivity of muscle cells and deficiencies of which are partly responsible for muscular dystrophy) have different versions (differing slightly in their DNA coding sequences) that can be attributed to different populations. For example, the B006 version of the dystrophin gene is known to come from Neanderthals, based on the previous whole-genome sequenging work. Yotova’s team found that 9% of non-African people in a survey of 6092 living humans possessed Neanderthal genes. Interestingly, the finding that Neanderthal genes were essentially absent in African populations supports the idea that migrant humans acquired the genes by interbreeding with Neanderthals after leaving Africa. Not surprisingly, the new genetic evidence supports what archaeological finds have been telling us all along regarding the spread of our species over the earth.

So there it is: the genetic smoking gun of sexual blending between our species and Neanderthals after we left Africa. Most importantly, the presence of Neanderthal genes in our own DNA shows not only that some human-Neanderthal couples could bear children, but that at least some of those children were fertile themselves. Clearly, there was enough similarity between our two species that we were not completely reproductively isolated from each other. Because of the strong competition between the two species, one was almost certainly not absorbed into the other and only a little genetic material from Neanderthals was retained in our genome. Nevertheless, this is a good example of gene flow not only from ancestors down to descendents within a species (called vertical transmission) but also between species, allowing genes to effectively jump from one species into another. The benefit of this union to our species may have been significant: following the population bottleneck in Africa around 50,000 years ago, genetic diversity of our species was severely reduced. A shallow gene pool is dangerous because it offers little variation in traits on which a species can lean when faced with a crisis such as infection. This is part of the problem associated with inbreeding. The injection of additional genetic material from Neanderthals may have replenished a bit of the lost variation.

This cross-species transfer of DNA by interbreeding is a remarkable phenomenon in itself, but in an upcoming post, I will highlight an even more fascinating phenomenon: horizontal gene transfer, by which species exchange genetic material with each other or splice their genes into another’s genome without even resorting to sexual reproduction. This phenomenon also causes ‘loops’ to appear in the tree of life, but these loops exist on a much grander scale.

For now, you may have a genetic excuse if somebody accuses you of dragging your knuckles.


1. Arnason U, Gullberg A, Janke A (1998) Molecular timing of primate divergences as estimated by two nonprimate calibration pointsJ. Mol. Evol. 47 (6): 718–27.doi:10.1007/PL00006431.

2. V. Yotova, J.-F. Lefebvre, C. Moreau, E. Gbeha, K. Hovhannesyan, S. Bourgeois, S. Bedarida, L. Azevedo, A. Amorim, T. Sarkisian, P. H. Avogbe, N. Chabi, M. H. Dicko, E. S. Kou’ Santa Amouzou, A. Sanni, J. Roberts-Thomson, B. Boettcher, R. J. Scott, D. Labuda. (2011) An X-Linked Haplotype of Neandertal Origin Is Present Among All Non-African Populations. Molecular Biology and Evolution 28: 1957 doi: 10.1093/molbev/msr024

3.  Belshaw, R; Pereira V; Katzourakis A; Talbot G; Paces J; Burt A; Tristem M. (2004) Long-term reinfection of the human genome by endogenous retroviruses. Proc Natl Acad Sci USA 101: 4894–99. doi:10.1073/pnas.0307800101

4. J. Cameron Thrash, Alex Boyd, Megan J. Huggett, Jana Grote, Paul Carini, Ryan J. Yoder, Barbara Robbertse, Joseph W. Spatafora, Michael S. Rappé, Stephen J. Giovannoni. (2011) Phylogenomic evidence for a common ancestor of mitochondria and the SAR11 clade. Scientific Reports 1 DOI: 10.1038/srep00013

5. Ceiridwen J. Edwards, Marc A. Suchard, Philippe Lemey, John J. Welch, Ian Barnes, Tara L. Fulton, Ross Barnett, Tamsin C. O’Connell, Peter Coxon, Nigel Monaghan et al. (2011) Ancient Hybridization and an Irish Origin for the Modern Polar Bear MatrilineCurrent Biology DOI: 10.1016/j.cub.2011.05.058

6. Reed DL, Smith VS, Hammond SL, Rogers AR, Clayton DH (2004) Genetic Analysis of Lice Supports Direct Contact between Modern and Archaic Humans. PLoS Biology 2: e340 doi:10.1371/journal.pbio.0020340

7. P. Mellars, J. C. French. (2011) Tenfold Population Increase in Western Europe at the Neandertal-to-Modern Human Transition. Science 333: 623 DOI: 10.1126/science.1206930

8. Letunic, I (2007) Interactive Tree Of Life (iTOL): an online tool for phylogenetic tree display and annotation. Bioinformatics 23(1): 127-8.

9. Green, Richard E.; et al. (2006) Analysis of one million base pairs of Neanderthal DNA. Nature 444: 330–336. doi:10.1038/nature05336

10. Noonan, James P.; et al. (2006) Sequencing and Analysis of Neanderthal Genomic DNA. Science 314: 1113–1118. doi:10.1126/science.1131412

11. Green, R.E.; et al. (2010) Draft full sequence of Neanderthal Genome. Science. 328: 710-722. DOI: 10.1126/science.1188021

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6 Responses to Cavemen in Your Genes

  1. Story Teller says:

    Fascinating, Julius! What a great post.

  2. Pingback: Evolution’s Usual Suspects: 1. Plagiarizing Wizards | Evolutionary Routes

  3. Great review! You actually overviewed some interesting things on your blog. I came across it by using Yahoo and I’ve got to admit that I already subscribed to the site, will be following you on my iphone 🙂

  4. Pingback: Frankenstein’s Batteries | Evolutionary Routes

  5. Andrea says:

    Amazing! Fascinating indeed, you did a great job keeping it interesting. Why were the Neanderthals eventually overtaken by us? They were bigger in size right? Were there a lot more of us to them? How would we know if humans are suspected to be Neanderthal in origin, is it based on physical appearance?

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