Source: The Guardian
A gene for this and a gene for that? No – we’re only beginning to unravel the complex genetics of human characteristics
You are a beautiful and unique snowflake. Soon there will be 7 billion humans on Earth, and yet with Dr Seussian confidence I can state that “there is no one alive who is Youer than You”. Even if you are an identical twin, you’ll know that you are not exactly the same as your sibling. This is borne out in the DNA of identical twins, whose genetic code diverges in small but measurable ways during their lives.
Uniqueness is literally in our DNA. The template for that individuality is in the 3bn units of genetic code that we carry in our cells. Couple that with the fact that our experiences and environments are unique, and influence how our genetic code plays out, and you have a model for irreproducibility. Scientists no longer say “nature versus nurture”, as it is clear that these two are not in conflict, but in collaboration. A better phrase is “nature via nurture”: the combination makes you you.
The attempt to understand our individuality, and our susceptibility to disease, was at the core of the grandest biological project in history. The Human Genome Project published its first results 10 years ago, a complete read-out of our genetic code. It was full of surprises, none more so than the seemingly simple question of how many genes humans have. Ewan Birney, now a major player in human genetics research, opened a book at a conference in 2001, and for a dollar per bet, the A-Z of top geneticists put their money where their mouths were. The highest predictions were in the many hundreds of thousands, and plenty were around the 80,000 mark. The real answer is that we have around 23,000 genes, similar to a mouse, and around the same number of parts as a double-decker bus.
This, as science so often does, resulted in many more questions than answers. Genes are the inherited units that make the proteins that all life is built by or of. But it turned out that less than 3% of our genome comprised genes. The rest was for years referred to as “junk DNA”, but it is very apparent now that it is far from rubbish.
And so now, after its completion, the Human Genome Project comes in for regular bashing for not delivering on its promises of enlightening disease and heredity. One of the key issues is that we scan through our DNA looking for clues to the genetic and heritable causes of complex diseases and traits, such as heart disease or height, and we find that we cannot account for large chunks of inheritance patterns. Yet.
This has become characterised as the case of the “missing heritability”. Detractors make it out to be a shocking crisis, and a damning indictment of genetics and the Human Genome Project. It is neither. It’s a fascinating scientific question that we will sort out soon. Mysterious? Yes, but only as much as any unanswered question in science. For a typically thoughtful and scientific dismantling of the arguments made on these pages and elsewhere, see geneticist Daniel MacArthur’s blog for Wired.
The history of genetics has led us towards thinking in a simplistic way about biology. In the 1980s, the first genes characterised were for devastating diseases such as cystic fibrosis and Huntington’s. They were the first because they are simple. But we now know that these single gene diseases are unusual. We are unique because we are complicated, and the genetics of most human characteristics are complex. So next time you see a headline that says “Scientists find the gene for x”, where x is DIY skills, risk-taking, being a liberal, or even eating a big bag of crisps, the truth is that they have not.
Nevertheless, the completion of the human genome was, I believe, one of humankind’s greatest endeavours. We either find out how things are, or we don’t. Personally, I like to know. It was not faultless by any means: it was expensive, and funds thrown at some areas of genetics have meant neglect to others, such as environmental risk factors for disease.
But the mistake that we often make is that it was an end point. In fact, the Human Genome Project was a pregnancy. It ended with the birth of the current era of genetics and medicine. To channel Donald Rumsfeld, back in 2001 we didn’t know how much we didn’t know. Ten years later, we now have a clue what we don’t yet know. The Human Genome Project may be finished, but understanding our genome is only just beginning. The only way we will ever understand our complexity is by more genome analysis: in the genes, in the increasingly misnamed “junk” DNA, and crucially, in many, many more people. We are unique, and biology is messy.