Human recipes

Humans have no more genes than mice, but there's no need to feel small. Recipes are more than lists of ingredients; the cooking makes us who we are
July 23, 2004

The more we find out about genomes, the more humiliating the news they bring us. The human genome turns out to be profoundly ordinary. We have known for decades that human beings have one fewer chromosome than chimpanzees, which should have been ample warning. We have known for years that grasshoppers have three times as much DNA per cell as we do, deep sea shrimps ten times, salamanders 20 times and African lungfish a staggering 40 times. But we still kidded ourselves until just the last few years that human beings would prove to have more genes, arranged in a more sophisticated way, than most other creatures. How else to explain our exquisite brains?

We have 25,000 genes (or recipes for protein molecules) which is the same as a mouse, just 6,000 more than a microscopic nematode worm and 15,000 fewer than a rice plant. However sophisticated our brains are, it is not reflected in our genes. This has led some to suggest that we have been exaggerating the role of genes in shaping our brains. In fact, it reminds us that recipes are more than lists of ingredients. How those ingredients are cooked is also crucial. And the instructions for cooking up a body are hidden in the genome too - between the genes themselves.

The deciphered text of the human genome is being joined by an increasing number of other animal volumes on the laboratory shelf. The mouse, rat and chimp genomes are done; the fly, worm and two fish genomes have been ready for a while. The chicken is coming soon; the kangaroo and the dog will follow. Each of them is a book of stupendous length and compendious tedium in itself, written in a four-letter alphabet with no punctuation, and consisting of sometimes upwards of 95 parts gobbledegook to two parts of sense - not exactly bedtime reading.

But comparing the genomes with each other is beginning to unveil some fascinating insights. There is, for example, an intriguing difference between animals and plants, to wit that plants tend to have more genes. This seems to touch upon a fundamentally different approach to innovation employed by the two kingdoms during evolution. When plants need a new trait (or rather, when natural selection imposes an advantage on a plant that has accidentally acquired a new trait), it happens by duplication and divergence: a duplicated version of an old gene evolves into the new one. That is how biologists thought all evolution happened. But animals seem to do it differently. They add a new switch, or "promoter sequence," to the front of an old gene, thus enabling the body to switch it on in a different place or at a different time: the same gene gets an additional job, in effect. The switch, too, is made of DNA text.

This leads to the most humiliating of all the discoveries consequent on genome reading. Human beings do not just have the same number of genes as a mouse; to all intents they have the same genes. But because they have slightly different switches on many of the genes, they can use them to make very different bodies. Coincidentally, this is similar to the way writers work. They use the same set of words in a different order to make different books. Even the numbers are similar. Shakespeare, for example, used 31,534 different words, though 14,376 appeared only once in his works. Omitting proper names, and allowing for different inflections ("know" and "knows"), most of the 4,686 words in Hamlet appear also in Othello and vice versa. The ten commonest words in Hamlet are the, and, to, if, I, you, my, a, in and it. The ten commonest words in Othello are I, and, the, to, you, of, my, a, that and in. The ten commonest words in King Lear are the, and, I, to, you, of, my, a, that and in.

A genome is constructed, like a Shakespeare play, from a few thousand interchangeable parts. The ten most commonly expressed genes in our bodies are also likely to be the ten most commonly expressed genes in a chimpanzee body, and many of them will also feature in the average fish.

It follows that it may soon be possible to identify the basic set of genes used by all mammals, just as it is possible to define Shakespeare's vocabulary. There then begins the formidable task of working out how slight differences in the place, time and volume of expression of those genes make one species unlike another. One example: the existence of a 400-letter phrase of repetitious text in the promoter of the vasopressin receptor gene of a prairie vole turns the rodent monogamous. That phrase alters the location of expression of the gene in the rodent's brain, making it active in the ventral pallidum, which contains a dopamine system that is responsible for addictive behaviour. A prairie vole therefore becomes "socially addicted" to its mate following sex, which is a grand way of saying it falls in love. A montane vole, lacking the 400-letter phrase, does not.

Human beings also have a repetitious phrase in this same region of the genome, though it is shorter than in prairie voles. As of this writing, the equivalent region of the chimpanzee genome has not yet been looked at. I predict it will be shorter than the human one, because humans commonly form long-term pair bonds, while chimpanzees commonly do not.

Multiply this example 10,000 or 20,000 times and you have explained how human nature differs from chimpanzee nature or vole nature. Make no mistake: this is theoretically possible. But in practice, it is an infinite task, because no sooner have you identified the "human" version than you will have to start defining how each individual slightly differs from it, and how each of those differences will cause you to recalculate the effect of the 25,000 other genes in the new context, and then the effect of those changes, and so on ad infinitum. As usual, far from closing mysteries, science opens new ones.