Fossil bones and footsteps and ruined homes are the solid facts of history, but the surest hints, the most enduring signs, lie in those miniscule genes. For a moment we protect them with our lives, then like relay runners with a baton, we pass them on to be carried by our descendents. There is a poetry in genetics which is more difficult to discern in broken bomes, and genes are the only unbroken living thread that weaves back and forth through all those boneyards.
Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease1, 2and is reduced in schizophrenia3, major depression4 and mesial temporal lobe epilepsy5. Whereas many brain imaging phenotypes are highly heritable6, 7, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10−16) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10−12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10−7).
In a very real sense human beings are machines constructed by the nucleic acids to arrange for the efficient replication of more nucleic acids. In a sense our strongest urges, noblest enterprises, most compelling necessities, and apparent free wills are all an expression of the information coded in the genetic material: We are, in a way, temporary ambulatory repositories for our nucleic acids. This does not deny our humanity; it does not prevent us from pursuing the good, the true, and the beautiful. But it would be a great mistake to ignore where we have come from in our attempt to determine where we are going.
Vestigial genes can go hand in hand with vestigial structures. We mammals evolved from reptilian ancestors that laid eggs. With the exceptions of the “monotremes” (the order of mammals that includes the Australian spiny anteater and duck-billed platypus), mammals have dispensed with egg-laying, and mothers nourish their young directly through the placenta instead of by providing a storehouse of yolk. And mammals carry three genes that, in reptiles and birds, produce the nutritious protein vitellogenin, which fills the yolk sac. But in virtually all mammals these genes are dead, totally inactivated by mutations. Only the egg-laying monotremes still produce vitellogenin, having one active and two dead genes. What’s more, mammals like ourselves still produce a yolk sac—but one that is vestigial and yolkless, a large, fluid-filled balloon attached to the fetal gut. In the second month of human pregnancy, it detaches from the embryo.
Another curious tale of dead genes involves our sense of smell, or rather our poor sense of smell, for humans are truly bad sniffers among land mammals. Nevertheless, we can still recognize over 10,000 different odors. How can we accomplish such a feat? Until recently, this was a completely mystery. The answer lies in our DNA—in our many olfactory receptor (OR) genes.
Our own sense of smell comes nowhere close to that of mice. One reason is that we express fewer OR genes—only about 400. But we still carry a total of 800 OR genes, which make up nearly 3 percent of our entire genome. And fully half of these are pseudogenes, permanently inactivated by mutations. The same is true for most other primates. How did this happen? Probably because we primates, who are active during the day, rely more on vision than on smell, and so don’t need to discriminate among so many odors. Unneeded genes eventually get bumped off by mutations. Predictably, primates with color vision, and hence greater discrimination of the environment, have more dead OR genes.
But the most striking example of the evolution—or de-evolution—of OR genes is the dolphin. Dolphins don’t need to detect volatile odors in air, since they do their business underwater, and they have a completely different set of genes for detecting waterborne chemicals. As one might predict, OR genes of dolphins are inactivated. In fact, 80 percent of them are inactivated. Hundreds of them still sit silently in the dolphin genome, mute testimony of evolution. And if you look at the DNA sequences of these dead dolphin genes, you’ll find that they resemble those of land mammals. This makes sense when we realize that dolphins evolved from land mammals whose OR genes became useless when they took to the water. This makes no sense if dolphins were specially created.
And the evolutionary prediction that we’ll find pseudogenes has been fulfilled—amply. Virtually every species harbors dead genes, many of them still active in its relatives. This implies that those genes were also active in a common ancestor, and were killed off in some descendants but not in others. Out of about 30,000 genes, for example, we humans carry more than 2,000 pseudogenes. Our genome—and that of other species— are truly well populated graveyards of dead genes.
The most famous human pseudogene is GLO, so called because in other species it produces an enzyme called L-gulono-y-lactone oxidase. This enzyme is used in making vitamin C (ascorbic acid) from the simple sugar glucose. Vitamin C is essential for proper metabolism, and virtually all mammals have the pathway to make it—all, that is, except for primates, fruit bats, and guinea pigs. In these species, vitamin C is obtained directly from their food, and normal diets usually have enough. If we don’t ingest enough vitamin C, we get sick: scurvy was common among fruit-deprived seamen of the nineteenth century. The reason why primates and these few other mammals don’t make their own vitamin C is because they don’t need to. Yet DNAsequencing tells us that primates still carry most of the genetic information needed to make the vitamin.
Only evolution and common ancestry can explain these facts. All mammals inherited a functional copy of the GLO gene. About forty million years ago, in the common ancestor of all primates, a gene that was no longer needed was inactivated by a mutation. All primates inherited that same mutation. After GLO was silenced, other mutations continued to occur in the gene that was no longer expressed. These mutations accumulated over time—they are harmless if they occur in genes that are already dead—and were passed on to descendant species. Since closer relatives share a common ancestor more recently, genes that change in a time-dependent way follow the pattern of common ancestry, leading to DNA sequences more similar in close than in distant relatives. This occurs whether or not a gene is dead. The sequence of YGLO in guinea pigs is so different because it was inactivated independently, in a lineage that had already diverged from that of primates. And YGLO is not unique in showing such patterns: there are many other such pseudogenes.
The software, the program. is responsible for organizing hardware, the organism. Yet throughout the process, it is the organism in its various stages of development that has to run the program. In other words, the hardware runs the software, whilst at the same time the software is generating the hardware.
Every animal and plant genome is subject to a constant bombardment of deleterious mutations: a hailstorm of attrition. It is a bit like the moon's surface, which becomes increasingly pitted with craters due to the steady bombardment of meteorites. With rare exceptions, every time a gene concerned with an eye, for example, is hit by a marauding mutation, the eye becomes a little less functional, a little less capable of seeing, a little less worthy of the name of eye. In an animal that lives in the light and uses the sense of sight, such deleterious mutations (the majority) are swiftly removed from the gene pool by natural selection.
But in total darkness the deleterious mutations that bombard the genes for making eyes are not penalized. Vision is impossible anyway. The eye of a cave salamander is like the moon, pitted with mutational craters that are never removed. The eye of a daylight-dwelling salamander is like the Earth, hit by mutations at the same rate as cave-dwellers' eyes, but with each deleterious mutation (crater) being cleaned off by natural selection (erosion). Of course, the story of the cavedweller's eye isn't only a negative one: positive selection comes in too, to favour the growth of protective skin over the vulnerable sockets of the optically deteriorating eyes.
A Mendelian gene is an all-or-nothing entity. When you were conceived, what you received from your father was not a substance, to be mixed with what you received from your mother as if mixing blue paint and red paint to make purple. If this were really how heredity worked (as people vaguely thought in Darwin's time) we'd all be a middling average, halfway between our two parents. In that case, all variation would rapidly disappear from the population (no matter how assiduously you mix purple paint with purple paint, you'll never reconstitute the original red and blue). In fact, of course, anybody can plainly see that there is no such intrinsic tendency for variation to decrease in a population. Mendel showed that this is because when paternal genes and maternal genes are combined in a child (he didn't use the word 'gene', which wasn't coined until 1909), it is not like blending paints, it is more like shuffling and reshuffling cards in a pack. Nowadays, we know that genes are lengths of DNA code, not physically separate like cards, but the principle remains valid. Genes don't blend; they shuffle. You could say they are shuffled badly, with groups of cards sticking together for several generations of shuffling before chance happens to split them.
Any one of your eggs (or sperms if you are male) contains either your father's version of a particular gene or your mother's version, not a blend of the two. And that particular gene came from one and only one of your four grandparents; and from one and only one of your eight greatgrandparents.
Let us suppose that women who have many chidren are far too busy to have much social life, and spend most of their time with their partners and family. The few other people they do see are likely to be other mothers with young children who already share at least some of their child-rearing memes. The more children they have the mor eyears they will spend this way. They will, therefore, have little time for spreading their own memes, including the ones concerned with family values and the pleasures of having lots of children.
On the other hand, women who have onlyh one or two children, or none at all, are far more likely to have jobs outside the home, to have an exciting social life, to use e-mail, to write books and papers and articles, to become politicians or broadcasters, or do any number of other things that will spread their memes, including the memes for birth control and the pleasures of a small family. These are the women whose pictures appear in the media, whose succss inspires others, and who provide role models for other women to copy.
There is a battle going on here -- a battle between memes and genes to take controle over the machinery of replication -- in this case a woman's body and mind. Any one person has only so much time and energy in their lifetime. They can divide it as they choose but they cannot have lots of children and devote maximal time and effort to spreading memes. This particular battle is played out largely in the lives of women and is becoming ever more important as women take a more prominent role in modern meme-driven society. My argument is simply this -- the women who devote more time to memes and less to genes are the more visible ones, and therefore the ones most likely to be copied. In the process, they are effectively encouraging more women to desert gene-spreading in favour of meme-spreading