What will the neanderthal genome teach us about human brain evolution?

skull.jpgPalaeoanthropologists at the Max Planck Institute, in collaboration with scientists at 454 Life Sciences Corp., of Branford, Connecticut, have begun a two-year project to sequence the neanderthal genome. The start of the Neanderthal Genome Project coincides with the 150th anniversary of the discovery of the specimen-type Homo neanderthalensis fossil in the Neander valley near Dusseldorf, Germany.

The ancestor of the chimpanzee, our closest living relative, split from ours about 7 million years ago. According to archaeological, palaeontological and molecular genetic data, modern humans and neanderthals both evolved from Homo erectus, with the two lineages diverging about 300,000 years ago. These data also support the hypothesis that modern humans arose relatively recently in Africa, and suggest that neanderthals were unlikely to have interbred with, or contributed any genes to, modern humans.

Neanderthals lived in Europe and Western Asia between approximately 300,000 to 28,000 years ago. They are believed to have been relatively sophisticated, but although there is evidence that neanderthals formed groups and buried their dead, they lacked many of the cognitive functions, such as higher reasoning, that we have. H. neanderthalensis was therefore either out-competed or driven to extinction by modern humans, whose emergence coincided with the disappearance of neanderthals.

We share 99% of our DNA with chimps. According to 454 Life Science’s Neanderthal Press Kit, “it is estimated that the Neanderthal shares 96% of the 1% difference with Homo sapiens. The neanderthal shares the remaining 4% of the difference with the chimpanzee.”

In other words, neanderthals were closer to us than they were to chimps, and, of all the hominid species that have existed, are the closest to humans. Sequencing and mapping of the neanderthal genome will therefore hopefully shed light on the relationship between that species and our own, and on evolution of the human brain.

Sequencing the neanderthal genome

“The analysis of the estimated 4% of genome variation that Neanderthal shares with the chimpanzee will help us to understand the evolution of characteristics specific to H. sapiens and perhaps even aspects of cognitive function,” says Svante Paabo, head of palaeogenetics research at the Max Planck Institute.

Obtaining samples of neanderthal DNA is very difficult. Neanderthal DNA is very scarce; in an earlier study, for example, 0.4 grams of neanderthal bone yielded between 1000- 1,500 fragments of DNA, each of 100 base pairs in length. These samples, obtained from a specimen dated at about 40,000 years old, had been degraded by hydrolysis and oxidation, and were contaminated with DNA from bacteria and fungi which start to decompose the body soon after death. Furthermore, neanderthal DNA is often contaminated with the DNA of those who excavated archaeological sites and discovered the skeletons, and of those who have handled the skeletons since their discovery.

The neanderthal genome is believed to be roughly the same size as that of humans – 3 billion base pairs. Paabo and his colleagues have already sequenced 1 million base pairs of DNA recovered from neanderthal bones found in Croatia. Samples from this same individual will be used in the neanderthal genome project. Jonathan Rothberg and Michael Egholm of 454 Life Sciences have also obtained permission to remove several grams of tissue from the right arm of the first neanderthal specimen discovered, to extract DNA samples for the project.

454 Life Sciences will use the Genome Sequencer 20 System to sequence the neanderthal genome. This is a high speed, ultra-high throughput sequencing technique using chips containing 1 million tiny wells. Because this technology uses DNA fragments of approximately 100 base pairs as a starting point, the degradation to which neanderthal DNA has been subjected over time is actually beneficial.

The DNA fragments are added to a mixture of water, polymerase chain reaction (PCR) reagents, a silicone-based oil and tiny plastic balls. Shaking the mixture creates an emulsion of small water droplets, many of which will contain a plastic ball with a single DNA fragment attached to it. The droplets are then placed in the wells on the chip, where the PCR reaction takes place. The amplified DNA is then sequenced using a fluorescence-based method, and the overlapping portions used to piece together the genomic sequence.

The relatively low projected cost of sequencing the Neanderthal genome – $500,000, compared to the billions of dollars needed to sequence the human genome – may make it more viable to sequence the genomes of people with rare or complex genetic disorders, in order to develop therapies.

The neanderthal and the human brain

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Knowledge of human brain evolution is rudimentary, and the little we do know about it so far comes largely from the use of immunohisto- and immunocytochemical techniques, combined with cytoarchitechtonic studies using classical methods, which have enabled studies in the comparative neuroanatomy of extant species.

The sequence of events in human evolution is still largely speculative and open to interpretation, and anthropologists have yet to agree upon a phylogentic tree of the human lineage. Similarly, the anatomical and functional specializations of the human brain, and the resultant bevahioural and cognitive capacities unique to humans, are also unknown. Molecular genetics is therefore one of the few techniques available for studying the neanderthal brain and comparing it to that of our species.

There is no doubt that it is the brain that makes our species unique among other animals. The versatility of our brain enabled early humans to manipulate the environment to a far greater extent than any other species; the invention of tools and weapons and the development of science and technology made H. sapiens the most successful (and destructive) species in the history of life on Earth.

The difference between human and neanderthal brains most likely explains the success of our species over neanderthals. In the Darwinian struggle for existence, the modifications that took place in the lineage leading to humans made our brains more dynamic; early humans were therefore more versatile and better adapted to their environment than were the neanderthals.

Some have hypothesized that functional asymmetry and handedness, which are closely related, are features that are unique to the human brain. There is, however, evidence that Homo habilis was right-handed, suggesting that neither of these features are in fact unique to the human brain, and that H. neanderthalensis was probably also right-handed and had a functionally asymmetrical brain. Language is a specialization that is often said to be unique to the human brain, but the existence of homologues of human speech centres in macaques would suggest that it is not. One cognitive capacity that may well be unique to humans is theory of mind, or the ability to understand that others have intentions.

The brain is a soft tissue and so does not fossilize. However, because of the tight packing of the brain within the skull, impressions of gyri and sulci are sometimes left on the inner surface of fossilized skulls, allowing palaeoneurologists to infer from endocasts something of the brain anatomy of extinct species. Nevertheless, the relationship between internal brain organization and brain function is as yet unclear, and what we can learn from palaeoneurology is therefore rather limited. A better understanding of the relationship between the structure of the cortex and cognitive abilities in extant species may help us to make inferences about neanderthals from palaeoneurological data, but this would require the discovery of intact, or nearly intact, neanderthal skulls.

The cranial capacity of neanderthals was, on average, 1450 cubic cm; this is larger than that of modern humans (1300 cubic cm). This difference in cranial capacity (and therefore brain size) is probably explained by the increased circuit complexity, energy-efficiency and plasticity of the human brain in comparison to that of the neanderthals, so that more computational power could be packed into a smaller space. These modifications were of enormous advantage to our species, and allowed for the brain functions that underlie the advanced cognitive processes of which human brains are capable.

A major problem concerning human brain evolution is the huge gap that exists between the emergence of humans and the emergence of human culture (approximately 10,000 years ago). During this time, the basic structure of the brain probably underwent cellular, laminar and connectional organization. This may have involved the successive addition of secondary, tertiary and quarternary cortical areas, especially in the prefrontal, visual, somatosensory and motor cortices. In other words, there was a shift from anatomical to functional (or physiological) evolution of the human brain. It is this re-organization which would have enabled modern humans to perform complex cognitive tasks.

Brodmann subdivided the human neocortex into 52 distinct functional areas, based on cytoarchitectonic differences observed in Nissl-stained samples. These areas process information in a hierarchical and parallel manner, and probably arose in succession as adaptations to the ecological niche inhabited by early modern humans. New cortical areas, comprising distinct functional units, would have required connections to existing areas as well as to subcortical structures.

Cortical processing units are known to contain roughly the same number of neurons (about 110) in most mammalian species, and, therefore, the cortical expansion that occurred during evolution of the human brain is more likely to have involved the addition of more of these units than an increase in complexity of pre-existing units. The presence in macaques of homologues of human speech centres would suggest that human brain evolution involved recruitment of pre-existing areas for new functions, rather than the de novo appearance of novel areas.

Several genes have already been implicated in the process of encephalization (the expansion of the neo-cortex relative to body mass) that took place during human evolution. Two of these, microcephalin and abnormal spindle-like microcephaly associated (ASPM) are known to regulate brain size during embryogenesis, and mutations in either cause retarded brain growth.

An examination of polymorphisms in these genes has revealed that certain variants of ASPM and microcephalin emerged 5, 800 and approximately 37, 000 years ago, respectively. This is a long time after the emergence of modern humans, which occurred about 200,000 years ago. The emergence of the microcephalin variant coincides with the spread of agriculture and the first use of written language. It is therefore tempting to think that there is a correlation between the emergence of this gene variant and human cognition.

Both of these genes are known to have undergone strong positive selective pressure during primate evolution, but the nature of that selection is still unknown. Both genes also underwent accelerated evolution in primate lineages in comparison to other lineages. In the primate lineages, this acceleration was greatest in the lineage that led to Homo sapiens, and was likely due to the selective pressure under which these variants were placed.

ASPM is involved in spindle formation; mutations in the coding sequence may have contributed to encephalization by causing an increase in the rate of cell division. An analysis of the differences between the genomes of humans and neanderthals could lead to the identification of new genes that may have played a role in evolution of the human brain.

Another gene implicated in human brain evolution is GLUD2, which encodes the enzyme glutamate deyhdrogenase. This gene is believed to have originated as a ‘retrocopy’ – that is, a DNA copy of the transcript for a related gene, which became incorporated into the genome, under the control of brain-specific regulatory sequences. GLUD2 first appeared in hominids 18-23 million years ago; the enzyme it encodes recycles the neurotransmitter glutamate, and is therefore thought to have permitted greater neuronal activity due to higher turnover of glutamate.

A comparison of the genomes of neanderthals and humans will not, of course, highlight any anatomical or functional differences between the human and neanderthal brain. It will, though, hopefully shed more light on the molecular events underlying evolution of the human brain, which in turn may allow researchers to infer more about the differences in the brains of the two species.

The neanderthal genome data may also enable the analysis of sequences regulating the expression of genes such as microcephalin, ASPM, GLUD2, and others in the neanderthal brain; a comparison of these sequences with those in the human genome may provide information on some of the differences in expression of brain-specific genes between neanderthals and humans.

Update: MIT Tech Review interviews 454 Life Science Vice President Michael Egholm. 

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8 thoughts on “What will the neanderthal genome teach us about human brain evolution?

  1. I consider myself to be quite Neanderthalish.
    I’ve got many of the physical traits, politically speaking I’d choose Left over Right any day of the week, plus I have a secret fetish for women in dominant roles, so I must be one of them.
    Besides, i understand no other intelligent way of co-habitating than helping each other.
    And I am a nomad, whether I like it or not.
    And guess what. Neanderthals are more prone to paranoia and other ailments of the soul than Cro-Magnons are.

    More here:
    http://lasparanoias.blogspot.com/2006/08/neanderthal-vs-cro-magnon.html
    (too long to post it here)

  2. I haven’t had a chance to read it properly, but this looks like a very interesting post.

    You claim that cerebral asymmetries can be explained by the co-existence of neanderthal and human characteristics/ genes/ traits. I’m not an anthropologist, but, as far as I know, there’s no evidence of interbreeding between neanderthals and early humans, although the absence of evidence in evidence of absence!

    Coon’s book, “The Origin of Races,” which you link to in your post, looks quite controversial. I’ll need to investigate further before I can comment in greater detail…

  3. Many errors were made with measurment of men and racial theories in history. It is better to avoid unrigourous statements I think.

    Richard Leakey explains in one of his books that brain lateralization is common to humans and chimps, for instance – and it happens more in masculine brains, sense their hormonal maturity comes later than feminine(?)- however, I can see no point at all.

  4. The “theory of mind” is not unique to man. It has long been shown in chimpanzees. It probably exists in most primates if not most mammals. This article is as a consequence a little unscientific and positively dated. Perhaps it too should itself go extinct like Neanderthal (but not for the reasons stated as it is in fact deemed he had most if not all of man’s higher mental faculties including language) for reason of its manifest inaccuracy.

  5. Sorry, I am not having a dig at you but for the reasons i’ve stated there are at least the two serious inaccuracies in your article and I am happy to provide references even though I am – like you – an amateur anthropologist but one perhaps a little less in the habit of swallowing cursory and rather homo-centric views of other primates and mammals. With the daunting double future threats to human civilization of peak oil and climate change now is not the time to haughtily look down upon our fellow creatures in this manner. One of them may well prove have been the forbear of a more successful successor on spaceship earth whose course of life still has another billion years or so to run until the sun burns them out…. Regards, Matthew.

  6. I would be interested in further discussion of brain evolution as it relates to the theory by Julian Jaynes in his 1976 (1990 last update) book The Origin of Consciousness in the Breakdown of the Bicameral Mind. The article states that the soft tissues of the brain do not fossilize, but I am wondering if there is any theory base for the development of the Corpus Callosum (CC) in H. Sapiens from say 30,000 years ago to present and similar theories about CC development in H. Neandertalensis or Chimpanzees for that matter. It could be that a faster or more extensive development of the CC was a principal factor in the eventual dominance of H. Sapiens and extinction of H. Neandertalensis. Jayne’s theory that the joining of the bicameral mind to create consciousness occurred about 3,000 years ago seems a stretch when the Egyptian/Mesopotamian and Chinese level of societal organization would require consciousness of a higher order than Jaynes would allow at least 7,000 or so years ago. Additional thoughts on race: Mitochondrial DNA evidence seems to show a common female ancestor for all H. Sapiens, probably in N. Africa and probably a high melanin content in that female’s skin. This evidence suggests all so-called racial characteristics arose through regional micro-evolution over the last 200,000 to 150,000 years ago (Dr. Douglas C. Wallace, et. al. Emory University School of Medicine in Atlanta). In my book there is no such thing as race! It is an outmoded way at looking at human beings.

  7. I too consider myself to be quite Neanderthalish in many of my characters.

    I am sorry for the Neanderthal’s extinction from this Planet probably by our ancestors, the Cro-Magnons.

    Recently I had a tough argument with a Christian pastor on religious grounds on the reasons why the Neanderthals disappeared.

    I had an opporunity to mention the Neanderthals on my book – “German Memories in Asia” (http://books.google.com/books?id=MrBi0ghiZN0C&dq=german+memories+asia)

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