Parasites are not only incredibly diverse; they are also incredibly successful. There are parasitic stretches of DNA in your own genes, some of which are called retrotransposons. Many of the parasitic stretches were originally viruses that entered our DNA. Most of them don't do us any harm. They just copy and insert themselves in other parts of our DNA, basically replicating themselves. Sometimes they hop into other species and replicate themselves in a new host. According to one estimate, roughly one-third to one-half of all human DNA is basically parasitic.

The genome is not a blueprint for constructing a body; it is a recipe for baking a body.

As the hox story illustrates, DNA promoters express themselves in the fourth dimension; their timing is all. A chimp has a different head from a human being not because it has a different blueprint for the head, but because it grows the jaws for longer and the cranium for less long than a human being. The difference is all timing.

The startling new truth that has emerged from the human genome - that animals evolve by adjusting the thermostats on the fronts of genes, enabling them to grow different parts of their bodies for longer - has profound implications for the nature-nurture debate. Suddenly nurture can start to express itself through nature.

Genetics has enticed a great many explorers during the past two decades. They have labored with fruit-flies and guinea-pigs, with sweet peas and corn, with thousands of animals and plants in fact, and they have made heredity no longer a mystery but an exact science to be ranked close behind physics and chemistry in definiteness of conception. One is inclined to believe, however, that the unique magnetic attraction of genetics lies in the vision of potential good which it holds for mankind rather than a circumscribed interest in the hereditary mechanisms of the lowly species used as laboratory material. If man had been found to be sharply demarcated from the rest of the occupants of the world, so that his heritage of physical form, of physiological function, and of mental attributes came about in a superior manner setting him apart as lord of creation, interest in the genetics of the humbler organisms—if one admits the truth—would have flagged severely. Biologists would have turned their attention largely to the ways of human heredity, in spite of the fact that the difficulties encountered would have rendered progress slow and uncertain. Since this was not the case, since the laws ruling the inheritance of the denizens of the garden and the inmates of the stable were found to be applicable to prince and potentate as well, one could shut himself up in his laboratory and labor to his heart's content, feeling certain that any truth which it fell to his lot to discover had a real human interest, after all.

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 disease^1, 2and is reduced in schizophrenia³, major depression⁴ and mesial temporal lobe epilepsy⁵. Whereas many brain imaging phenotypes are highly heritable^6, 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).

We are now witnessing, after the slow fermentation of fifty years, a concentration of technical power aimed at the essential determinants of heredity, development and disease. This concentration is made possible by the common function of nucleic acids as the molecular midwife of all reproductive particles. Indeed it is the nucleic acids which, in spite of their chemical obscurity, are giving to biology a unity which has so far been lacking, a chemical unity.

My own thinking (and that of many of my colleagues) is based on two general principles, which I shall call the Sequence Hypothesis and the Central Dogma. The direct evidence for both of them is negligible, but I have found them to be of great help in getting to grips with these very complex problems. I present them here in the hope that others can make similar use of them. Their speculative nature is emphasized by their names. It is an instructive exercise to attempt to build a useful theory without using them. One generally ends in the wilderness.

The Sequence Hypothesis

This has already been referred to a number of times. In its simplest form it assumes that the specificity of a piece of nucleic acid is expressed solely by the sequence of its bases, and that this sequence is a (simple) code for the amino acid sequence of a particular protein...

The Central Dogma

This states that once 'information' has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein. This is by no means universally held—Sir Macfarlane Burnet, for example, does not subscribe to it—but many workers now think along these lines. As far as I know it has not been explicitly stated before.

[Locating, from scratch, the gene related to a disease is like] trying to find a burned-out light bulb in a house located somewhere between the East and West coasts without knowing the state, much less the town or street the house is on.

In a sense, genetics grew up as an orphan. In the beginning botanists and zoologists were often indifferent and sometimes hostile toward it. 'Genetics deals only with superficial characters', it was often said. Biochemists likewise paid it little heed in its early days. They, especially medical biochemists, knew of Garrod's inborn errors of metabolism and no doubt appreciated them in the biochemical sense and as diseases; but the biological world was inadequately prepared to appreciate fully the significance of his investigations and his thinking. Geneticists, it should be said, tended to be preoccupied mainly with the mechanisms by which genetic material is transmitted from one generation to, the next.

Knowing what we now know about living systems—how they replicate and how they mutate—we are beginning to know how to control their evolutionary futures. To a considerable extent we now do that with the plants we cultivate and the animals we domesticate. This is, in fact, a standard application of genetics today. We could even go further, for there is no reason why we cannot in the same way direct our own evolutionary futures. I wish to emphasize, however—and emphatically—that whether we should do this and, if so, how, are not questions science alone can answer. They are for society as a whole to think about. Scientists can say what the consequences might be, but they are not justified in going further except as responsible members of society.

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.

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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.