We have duplications of genes in combinations that are unique to humans. And we have versions of genes that are also found only in us. We can also talk about what specific genes are doing in us.
We’ve compared the behaviors of animals with us in this book, and we can extend this to genetic comparisons too. We have many genes that are broadly shared with all organisms, whose origins are billions of years old. These tend to encode very basic bits of biochemistry. There are genes that we share with all animals, or all mammals, or all primates, or all great apes. Genetic genealogies closely resemble evolutionary family trees, but not perfectly. This is largely because evolutionary family trees aren’t shaped like trees. After only a few generations back they become matted webs, as ancestors occupy more than one position on your pedigree. Here’s an extreme example from our prehistory: the lineages of Homo sapiens and Homo neanderthalensis split some 600,000 years ago. Both evolved independently for all that time apart, until 50,000 years ago when Homo sapiens turned up in their lands, and we all had sex. We know this because we’ve sequenced the Neanderthal genome, and if you are European, you have DNA that is clearly from them, and was introduced at that time. Within a few thousand years, they were gone, but their DNA remains alive in us. Some of that
Neanderthal DNA subtly influences the biology of living Europeans, including skin and hair pigmentation, height, sleeping patterns, and even a predisposition for smoking, even though that vice wouldn’t be invented for a few hundred millennia.* In terms of an evolutionary tree, therefore, this introgression of Neanderthal DNA into you, if indeed you are of European descent, represents a loop. Trees don’t have loops. Though genes are mostly passed down family trees, the trees themselves can be messy, and genes can enter a lineage from other directions, from ancestral cousins, or even, as we have seen, from a virus. They can also be lost in time just via the normal process by which genes get shuffled every time an egg or sperm is made.
Despite the messiness of ancestry, we can legitimately compare DNA in us, the Denisovans, Neanderthals and the other great apes, and try to infer whether the differences we see are significant.
HACNS1 isn’t actually a gene.† It’s a stretch of 546 letters of DNA called an “enhancer,” sixteen of which are specifically different from what chimpanzees have. It’s not a gene because it doesn’t encode a protein, but what enhancers (or other bits of non-coding DNA) do is act as regulators for genes. Every cell with a nucleus contains every gene, but not every cell needs every gene to be active at any one time. Enhancers tend to sit near the beginning of genes and act as instructions for that gene to be activated. Generally, we read sentences sequentially, from beginning to end and, in English, left to right. Genes are dotted all over the genome and can be read in any direction, in any order, on any chromosome, because unlike a book, they are never written in one go, or designed with a plan. A gene on chromosome 1 might activate a gene on chromosome 22. Enhancers and other regulatory bits of DNA control this apparent chaos.
We can test the function of an enhancer by looking at where and when it is active, and experimentally switching in mice embryos between the chimpanzee version and the human version. HACNS1 is active in a lot of tissues, including the brain, but it is buzzing with activity in the developing forelimbs, particularly in the tips of the bud that will develop into the paw. The same experiment with the chimp version of HACNS1 didn’t show great activity in the same place. There’s a similar pattern in the hindlimb buds too. As this chunk of DNA is an enhancer and not a gene itself, increased activity in the hands and feet is indicative of its role in turning on other genes, which are likely to be different in the hands and feet. Dexterity in human hands is essential for the tool crafting that we can do more skillfully than the other great apes, notably in the ability to rotate the thumb (which is longer in us relative to our other four fingers). Conversely, lack of dexterity and shortened digits in the feet was essential to our becoming bipedal. It’s a striking theory that the rapid evolution of this short bit of DNA has had a significant role in altering the morphology of our hands and feet in ways that have become distinctly and uniquely human.
I could list a few more genes here that are intriguing clues to the genetic basis of uniquely human characteristics, and lots more will be discovered soon enough. Genes involved in brain development are particularly intriguing, because we have big, interesting brains.
Then again, because we have big, interesting brains, a huge number of genes are involved in the growth and maintenance of our neural matter. Some will promote the growth of new neurons, others the flourishing of connections between neurons. Some will be active in specific areas of the brain, especially in the neocortex, where so much of our insight and personality are centered. Many of these candidates will do many of these things and more, because evolution tinkers, and adapting and reusing something that already exists is easier and more efficient than inventing something from scratch.
Individual genes are often fascinating in their own right—though plenty are rather boring—and it is important that alongside the other 20,000 genes that every human bears, we continue to work out what they do, how they evolved, how they interact with the rest of our biology, and what happens when they go wrong. We also have to look at how they work with each other in the context of a functioning body.