Working out what makes us human.

By Peter Dearden 20/12/2013

Peter K. Dearden.

One key question in biology is what makes us different as a species. Humans have a remarkable set of adaptations that distinguish us from even our closest living relatives. We walk upright, we have larger brains, we use language, and we are consummate tool-makers and users. From the point of view of an alien, perhaps, these differences may be subtle, but they are key to our spread around this planet, and the ability, for better or worse, to modify our environment. These differences must be encoded somewhere in our genes. Something about the way our DNA works, or is organised, must underpin these differences in our biology. Such differences are key targets for scientists seeking to understand the biology of our species.

Before we sequenced the human genome, we thought that we probably had hundreds of thousands of genes in our genome, as compared to the 13,000 odd in flies and worms. Sequencing our genome  indicated that actually we have around 20,000, and that that number is pretty much the same in all mammals. Sequencing the genomes of the Gorilla  and the Chimpanzee showed that our genomes are very similar to theirs. Comparing the DNA sequence of genes in our genome with those in other primates indicates that we do not have a huge pile of ‘extra’ genes that make us humans, or help us run our huge brains. Indeed it is very hard to identify any genes that are only in our genome, and not in any other species. We do have variants of genes, however, our version of a gene may differ slightly from the version in other primates. Of course this is true within our species, different people often have different versions of the same gene.

We are beginning to understand, however, that the differences between species may not be due to differences within genes, but in the way genes are turned on or off; the regulation of genes. While the best-known examples are in insects (for example see here ) changes in gene regulation, with no change in the genes themselves, may underlie much species difference.

Recently the knowledge about our closest relatives has been dramatically improved. Advances in DNA sequencing allowed us to sequence the genome of a Neanderthal despite them being extinct and only their bone fragments remaining. Even more excitingly, such sequencing has even identified new as previously unknown human species, including the mysterious Denisovans. Now a much more complete version of the Neanderthal genome has been produced, by a group in Germany. By sequencing the DNA from a toe bone, this group has show that the bone is from a Neanderthal, and increased the amount of sequence data from this species. The authors of this paper report all kinds of interesting things, but towards the end of the paper, they start to talk about the genetic differences between us and Neanderthals. It’s thrilling!

The authors determine that we have 96 differences, within only 87 protein-coding genes, from Neanderthals. Outside genes, they catalogue around 3000 differences that might change the regulation of genes. We can only hope that somewhere within this catalogue are the genetic determinants of human-ness.

But wait, how different are Neanderthals to us? They made tools, they may have had language, they walked upright, they buried their dead, and we had sex with them. Should we perhaps we be looking for changes that we share with Neanderthals that aren’t in more distant relatives?

More importantly, how can we ever know which of those changes in the genome make us us? We could never do an experiment that would put a human version of a gene or regulatory sequence in a Neanderthal, because they are extinct. Nor would we modify a human genome to put in a Neanderthal sequence, because of the obvious ethical issues. If we cannot test what these differences in our genome do, how can we ever know which bits of our genome encode our unique biology, and which encode the unique biology of our relatives?

0 Responses to “Working out what makes us human.”

  • “Should we perhaps we be looking for changes that we share with Neanderthals that aren’t in more distant relatives?”

    I don’t have a copy of the paper to read, but let me ruminate late at night all the same!

    My first thought was to try a variant of what you suggest but using the data from the 1000 genomes project* to identify regions common to all humans and compare these ‘blocks’ of highly similar regions with other species in the same way as you’re saying.

    I also can’t help thinking something along these lines must, surely, have already been done as it’s too obvious and the authors have no doubt thought along similar lines esp. as the abstract says they use 25 human genomes in their data.

    Another of far too many papers that are begging to be read… thanks for the post.

    * A collection of a little more than a thousand human genome sequences that is giving us some idea of what genetic differences there are between people. (The commonly-found differences.)

  • Nor is it limited to biology and genes, this perhaps is the thing that most miss or do not understand. Our genetics and biology allow us to take the next step, that of social, informational, knowledge evolution which is even now moving beyond biology into our creations, our machines.

  • Kenny, I think you are correct. I think (with little evidence) that most of the ‘human specific traits’ are emergent properties of having a larger brain etc. The abilities that we have are not directly encoded in our DNA, but arise as a result of quite subtle changes in our development that perhaps produce more neurons, that make more connections etc etc.

  • Grant- the key I reckon is in diversity. You are correct that you need to use a lot of human genomes to capture our diversity, but also then more Neanderthal and chimp genomes.
    Even more problematic is that these seem kind of arbitrary species. Biologically we have a series of adapting and diverging populations, which are clearly not reproductively isolated. This means the diversity question is even more important to understand.

  • I wonder if the things that make humans genetically distinctive were not uniquely present in ‘our’ lineage before the time of the Denisovans and neanderthals, or are perhaps illusory or unnecessary. Several things suggest this. Firstly, the cultural diversity present in the world now (and in the recent past) is large and it seems unlikely that there is any genetic basis to much, if any, of this. Are any differences between ‘human’ and neanderthal cultural references greater than current diversity?The absence of clearly Denisovan artefacts suggests that they either left nothing, or there is no clear distinction between what they left and what other humans created. In either case this seems to mitigate against a genetic basis for such cultural diversity.

    Secondly, we know there is considerable difficulty in correlating reasonably clear phenotypes likely to arise from an underlying genotype with specific genetic variation (ranging from height to susceptibility to gout). That suggests to me that any attempt to correlate cultural phenotypes with some kind of much more diffuse genotype is unlikely to be successful.

    That there is a relationship between nature and nurture is, perhaps, beginning to be understood. Perhaps environmental variation comes in two forms: those things in the environment to which we are exposed, and the cultural environment that we collectively create for ourselves and which is transmitted in a non-genetic way.

    There may be some kind of genetic predisposition to do this (and it is tempting to suggest that innovation might be part of that trend), but perhaps such a characteristic is not needed. We only need to consider how easily cultural developments transfer among cultures to realise that extra-genetic mechanisms might be sufficient.

    Testing that experimentally might be difficult. However, there are many studies looking at how technology, innovation and concepts spread among culturally distinct groups and perhaps that is where we should start.