You are the current owner of one of the great wonders of the natural world: a large genome, copied almost perfectly from your parents to you, without which you would not be here. And when I say large, I mean large - 3,400,000,000 large to be more accurate. This, give or take a bit, is the size of your genome measured in the number of nucleotides, the Lego-like building blocks of DNA. Buried somewhere in this DNA are genes that code for proteins, about 25,000 of them, spread out over your 23 chromosomes.
Darwin knew nothing of genes, let alone genomes. He knew that children resemble their parents, but other than this his understanding of genetics was, shall we say, limited. What then would he have made of the Human Genome Project? Vindicated? Yes. Excited? Probably. Gob-smackingly bemused? Almost certainly.
In On the Origin of Species, Darwin made two claims: that there is continuity of species, with each species today being descendants of prior ones, and that natural selection is the mechanism by which species change. In our DNA there is evidence for both, but at the same time our genome is a head-scratching evolutionary enigma.
To see how the continuity of species is written large in our DNA, just take one of your genes. You can typically find a copy of that same gene in many different species. Look closely at the genes and you see just what Darwin would have predicted: our version of the gene is much more similar to the chimp version than, say, to mouse, rat, fish or fly versions. Likewise, the mouse gene is most similar to the rat copy. Contained in the patterns of similarity is the history of the continuity of species - of descent with modification. Darwin was right, species were not just plonked on earth, each individually created.
Genomes have also taught us, though, that natural selection is often an enforcer of continuity rather than change. Our genome, like all others, is a conservative being. Most of what genes do is basic maintenance work - the same in just about all species. Consequently, like a perfectly engineered BMW engine, random tweaks often make things worse rather than better. Such changes tend to result in genetic diseases such as cystic fibrosis.
In the cruel natural world the unfortunate carriers of such genetic mutations die out before they can leave any descendants. And over the long term this leaves a footprint in the genome - a region of DNA that is very similar between species.
So, not surprisingly, the most conserved parts of our genome are protein-coding genes themselves - changes here really make a difference. Close by are stretches of DNA involved in switching genes on and off. Again, these regions differ little between species. It all fits a Darwinian picture rather nicely.
Comparing our genome to those of other species also shows us where natural selection has been most active in making changes. To do this we look for the genes which differ most between species. Trawl any genome this way and the same sorts of genes typically turn up - genes involved in resistance to viruses, bacteria, worms or other parasites. All organisms play an evolutionary game of ping-pong with their bugs. Just as bacteria evolve to be resistant to the antibiotics we throw at them, so we have evolved resistance to bacteria, only for them to counter-evolve, leading to selection favouring a change in us... and so on.
Unusually big brains
But our genome tells another, more human-centred story. If we look for genes under selection exclusively in the human lineage, top of the list is the gene HAR1, involved in making our unusually big brains. There are two changes in the gene's 118 DNA letters between chickens and chimps, but 18 changes between chimps and us. Another gene to show human-specific evolutionary acceleration is FOXP2. It is disrupted in some people with a language impairment and is involved in the way many other species vocalise - for example, birds singing.
Genetic differences between human populations are also telling scientists about more recent evolution. The ability of adults to digest milk, for example, has evolved independently at least twice in human history.
All, then, seems rosy in a Darwinian view of the human genome. So where is the bafflement? Look again at the numbers: 25,000 genes, each about 1,500 letters long, in a genome of 3.4bn nucleotides. This means just 1 or 2% of our genome actually codes for protein. Our genes are like railway stations separated from each other by vast stretches of train track. What, if anything, does this apparently surplus DNA do? Maybe we need to stop considering necessity and start considering chance?
Imagine a new mutation in your genome (we are each born with around 100). Initially you, and you alone, have this change. What if this has no significant effect on you? Can this mutation increase in frequency in a population to eventually become one of the changes that we would see between us and other species?
A race between drunks
To see how chance could be important, imagine a race between drunks. At each step, each drunk is as likely to walk forwards as backwards. Place our drunks on the start line of a 100-metre track and add one extra rule. A drunk who steps back over the start line is out of the race. The drunks in the analogy are random changes to DNA and their backwards and forwards steps represent changes in the frequency of those mutations in a population with each generation.
Because they begin close to the start line, most drunks will be quickly eliminated. But some, by chance, will make it to the finish, not because they were good runners but because they happened to go forwards more often than backwards. This is the neutralist view of evolution - lucky genes, not selfish genes.
Among those studying genomes, the neutralist view has for many years held sway. Most of the DNA sitting between the genes was considered "junk", acquired because natural selection did not care which randomly walking drunks won and which lost. We assumed that mutations that changed a gene's sequence but not the protein it produced were like this. As were changes to a gene's position in the genome. Our genome, we thought, was more Trabant than BMW - pretty rubbish, prone to breakdown, but it just about got the job done.
With more data accumulating, this view is now being challenged. Recent studies show that there are many bits of the supposed junk DNA whose sequence is ultra-conserved throughout the vertebrates. Precisely why they are conserved remains unclear, but junk they are not. We also now know that genes are not randomly located on the chromosomes. Even mutations that change the sequence of a gene without altering the protein it codes for can, we now know, be lethal, because they can interfere with the way the protein is made. Far from being apathetic, natural selection cares very much about these mutations.
But perhaps most surprising of all are results from studies looking to see where the genome is active. We thought the genome would only be operating where the protein coding genes are - the special 2%. We could not have been more wrong. Current estimates suggest that the great majority of the genome, "junk" included, is active.
One thing is clear: there is more to genomes than genes. Some of the activity is not directly related to the manufacture of protein, but is instead involved in the regulation of that process by mechanisms that we are only now starting to unravel. Whether this explains all of the activity is far from clear. Trabby or beamer, either way your genome may be the most enigmatic thing about you.
Laurence D. Hurst is professor of evolutionary genetics at the University of Bath