Your genes specify everything about you – whether you’ll be homosexual or heterosexual, what kinds of diseases you will be susceptible to, how long you will live … even what make of car you will prefer. Now that science has sequenced the human genome, the DNA sequence for a person, we know all of the information required to make a human, so we know everything there is to know about how human beings work.
Some of us will be able to add that most DNA isn’t in the form of genes, but is just ‘junk’ left over from some distant part of our evolutionary history. The junk gets a free ride on the reproductive roller-coaster, and it survives because it is ‘selfish’ and doesn’t care what happens to anything except itself.
Here ends the folk view of evolution. We’ve parodied it a little, but not by as much as you might hope. The first part is a lie-to-children about natural selection; the second part is uncomfortably close to ‘neo-Darwinism’, which for most of the past 50 years has been the accepted intellectual heir to The Origin. Darwin told us what happens in evolution; neo-Darwinism tells us how it happens, and how it happens is DNA.
There’s no question that DNA is central to life on Earth. But virtually every month, new discoveries are being made that profoundly change our view of evolution, genetics, and the growth and diversification of living creatures. This is a vast topic, and the best we can do here is to show you a few significant discoveries and explain why they are significant.
Just as physics replaced Newton by Einstein, there has been a major revolution in the basic tenets of biology, so we now have a different, more universal view of what drives evolution. The ‘folk’ evolutionary viewpoint: ‘I’ve got this new mutation. I have become a new kind of creature. Is it going to do me any good?’ is not the way modern biologists think.
There are many things wrong with our folk-evolution story. In fact we’ve deliberately constructed it so that every single detail is wrong. However, it’s not very different from many accounts in popular science books and television programmes. It assumes that primitive animals alive today are our ancestors, when they are our cousins. It assumes that we ‘came from’ apes, when of course the ape-like ancestor of man is the same creature as the man-like ancestor of modern apes. More seriously, it assumes that mutations in the genetic material, the changes that natural selection has to work on – indeed, to select among – are checked out as soon as they appear, and labelled ‘bad’ (the organism dies, or at least fails to breed) or ‘good’ (the animal contributes its progeny to the future).
Until the early 1960s, that was what most biologists thought too. Indeed, two very famous biologists, J.B.S. Haldane and Sir Ronald Fisher, produced important papers in the mid-1950s espousing just that view. In a population of about 1000 organisms, they believed, only about a third of the breeding population could be ‘lost’ to bad gene variants, or could be ousted by organisms carrying better versions, without the population moving towards extinction. They calculated that only about ten genes could have variants (known as ‘alleles’) that were increasing or decreasing as proportions of the population. Perhaps twenty genes might be changing in this way if they were not very different in ‘fitness’ from the regular alleles. This picture of the population implied that almost all organisms in a given species must have pretty much the same genetic make-up, except for a few which carried the good alleles coming in, and winning, or the bad alleles on the way out.1 These exceptions were mutants, famously and stupidly portrayed in many SF films.
However, in the early 1960s Richard Lewontin’s group exploited a new way to investigate the genetics of wild (or indeed any) organisms. They looked at how many versions of common proteins they could find in the blood, or in cell extracts. If there was just one version, the organism had received the same allele from both of its parents: the technical term here is ‘homozygous’. If there were two versions, it had received different ones from each parent, and so was ‘heterozygous’.
What they found was totally incompatible with the Fisher-Haldane picture.
They found, and this has been amply confirmed in thousands of wild populations since, that in most organisms, about ten per cent of genes are heterozygous. We now know, thanks to the Human Genome Project, that human beings have about 34,000 genes. So about 3400 are heterozygous, in any individual, instead of the ten or so predicted by Haldane and Fisher.
Furthermore, if many different organisms are sampled, it turns out that about one-third of all genes have variant alleles. Some are rare, but many of them occur in more than one per cent of the population.
There is no way that this real-world picture of the genetic structure of populations can be reconciled with the classical view of population genetics. Nearly all current natural selection must be discriminating between different combinations of ancient mutations. It’s not a matter of a new mutation arriving and the result being immediately subjected to selection: instead, that mutation must typically hang around, for millions of years, until eventually it ends up playing a role that makes enough of a difference for natural selection to notice, and react.
With hindsight, it is now obvious that all currently existing breeds of dog must have been ‘available’ – in the sense that the necessary alleles already existed, somewhere in the population – in the original domesticated wolves. There simply hasn’t been time to accumulate the necessary mutations purely in modern dogs. Darwin knew about the amount of cryptic and overt variation in pigeons, too. But his successors, hot on the trail of the molecular basis of life, forgot about wolves and pigeons. They pretty much forgot about cells. DNA was complicated enough: cell biology was impossible, and as for understanding an organism …
Lewontin’s discovery was a significant turning point in our understanding of heredity and evolution. It was at least as radical as the much better publicised revolution that replaced Newton’s physics with Einstein’s, and it was arguably more important. We will see that in the last year or so there has been another, even more radical, revision of our thinking about the control of cell biology and development by the genes. The whole dogma about DNA, messenger RNA, and proteins has been given a reality check, and science’s internal ‘auditors’ have rendered it as archaic as Fisher’s population genetics.
It is commonly assumed – not only by the average television producer of pop science half-hours, but also by most popular science book authors – that now we know about DNA, the ‘secret of life’, evolution and its mechanisms are an open book. Soon after the discovery of DNA’s structure and mechanism of replication by James Watson and Francis Crick, in the late 1950s, the media – and biology textbooks at all levels – were beginning to refer to it as the ‘Blueprint for Life’. Many books, culminating with Dawkins’s The Selfish Gene in the 1970s, promoted the view that by knowing about the mechanism of heredity, we had found the key to all of the important puzzles of biology and medicine, especially evolution.
There was soon to be a major tragedy, resulting from a medical application of that mistaken view. The sedative thalidomide was increasingly being prescribed, and bought over the counter, to treat nausea and other minor discomforts of the early weeks of pregnancy. Only later was it discovered that in a small proportion of cases, thalidomide could cause a type of birth defect known as phocomelia, in which arms and legs are replaced by partially developed versions that resemble a seal’s flippers.
It took a while for anyone to notice, partly because few general practitioners had experience of phocomelia before 1957. In fart, very few of them had ever seen a case at all, but after 1957 they began to see two or three in a year. A second reason was that it was very difficult to tie this defect to a particular potion or treatment: pregnant women famously take a great variety of dietary additives, and often they don’t remember precisely what they’ve taken. Nevertheless, by 196l some medical detective work had tied the spate of phocomelia down to thalidomide.
American doctors congratulated themselves on having missed out on the pathology, because Frances Kelsey, a medical wo
rker for the Food and Drug Administration, had expressed misgivings about the original animal testing of the drug. Her misgivings eventually turned out to have been unfounded, but they did save much suffering in the USA. She noticed that the drug had not been tested on pregnant animals, because at that time such tests were not required. Everyone knew that the embryo has its own blueprint for development, quite separate from that of the mother. However, embryologists trained in biology departments, as distinct from medical embryologists, knew about the work of Cecil Stockard, Edward Conklin, and other embryologists of the 1920s. They had shown that many common chemicals could caused monstrous developmental defects. For instance, lithium salts easily induced cyclopia, a single central eye, in fish embryos. These alternative developmental paths, induced by chemical changes, have taught us a lot about the biological development of organisms, and how it is controlled.
They have also taught us that an organism’s development is not rigidly determined by the DNA of its cells. Environmental insults can push the course of development along pathological paths. In addition, the genetics of organisms, particularly wild organisms, are usually organised so that ‘normal’ development happens despite a variety of environmental insults, and even despite changes in some of the genes. This so-called ‘canalised’ development is very important for evolutionary processes, because there are always temperature variations, chemical imbalances and assaults, parasitic bacteria and viruses; the growing organism must be ‘buffered’ against these variations. It must have versatile developmental paths to ensure that the ‘same’ well-adapted creature is produced, whatever the environment is doing. Within reasonable limits, at any rate.
There are many developmental tactics and strategies that help to accomplish this. They range from simple tricks like the HSP90 protein to the very clever mammalian trade-off.
HSP stands for ‘heat shock protein’. There are about 30 of these proteins, and they are produced in most cells in response to a sudden, not very severe, change of temperature. A different array of proteins is produced in response to other shocks; this one is called HSP90 because of where it sits in a much longer list of cell proteins. HSP90, like most HSPs, is a chaperonin: its job is to hug other proteins during their construction, so that when the long line of amino acids folds up it achieves the ‘right’ shape. HSP90 is very good at making the ‘right’ shape – even if the gene that specifies the chaperoned protein has accumulated a lot of mutations. So the resulting organism doesn’t ‘notice’ the mutations; the protein is ‘normal’ and the organism looks and behaves just like its ancestral form.
However, if there’s a heat shock or other emergency during development, HSP90 is diverted from its role as chaperonin, and other less powerful chaperonins permit the mutational differences to be expressed in most of the progeny. The effect this has on evolution is to keep the organisms much the same until there’s an environmental stress, when suddenly, in one generation, lots of previously hidden, but hereditable, variation appears.
Most books that describe evolution seem to assume that every time there’s a mutation, the environment promptly gets to judge it good or bad … but one little trick, HSP90, which is present in most animals and many bacteria, makes nonsense of that assertion. And from Lewontin’s discovery that a third of genes have common variants in wild populations, and that all organisms carry lots of them, it is clear that ancient mutations are continually being tested in different modern combinations, while the potential effects of more recent mutations are being cloaked by HSP90 and its ilk.
The trick employed by mammals is much more complex and far-reaching. They reorganised their genes, and got rid of a lot of genetic complication that their amphibian ancestors relied on, by adopting a new and more controlled developmental strategy.
Most frogs and fishes, whose eggs usually encounter great differences and changes of temperature during each embryology, ensure that the ‘same’ larva, and then adult, results. Think of frog spawn in a frozen English pond, warming up to 35°C during the day while the delicate early development proceeds; then the little hatchling tadpoles have to endure these temperature changes. Now think of the frogs that so few of the tadpoles become.
Most chemical reactions, including many biochemical ones, happen at different rates if the temperature is different. You only get a frog if all the different developmental processes fit together effectively, and timing is crucial. So how does frog development work at all, given that the environment is changing so quickly and repeatedly?
The answer is that the frog genome ‘contains’ many different contingency plans, for many different environmental scenarios. There are many different versions of each of the enzymes and other proteins that frog development requires. All of them are put into the egg while it is in mother frog’s ovary. There are perhaps as many as ten versions of each, appropriate to different temperatures (fast enzymes for low temperatures, sluggish ones for higher temperatures, to keep the duration of development much the same2), and they have ‘labels’ on the packages that make them, so the embryo can choose which one to use according to its temperature. Animals whose development must be buffered in this way use a lot of their genetic programme to set up contingency plans for many other variables, in addition to temperature.
The mammals cleverly avoided all of this faffing around, by making their females thermostatically controlled – ‘warm-blooded’. What counts is not the warmth of the blood, but the system that maintains it at a constant temperature. The beautifully controlled uterus keeps all kinds of other variables away from the embryos, too, from poisons to predators. It probably ‘costs’ much less in DNA programming to adopt this strategy, too.
This trick, evolved by the mammals, carries an important message. To ask how much information passes across the generations in the DNA blueprint, as textbooks and sophisticated research manuals often do, is to miss the point. How the genes and proteins are used is far more important, and far more interesting, than how many genes or proteins there are in a given creature. Lungfishes and some salamanders, even some amoebas, have more than fifty times as much DNA as we mammals do. What does this say about how complex these creatures are, compared to us?
Absolutely nothing.
Tricks like HSP90, and strategies like warm-bloodedness and keeping development inside the mother, mean that bean-counting of DNA ‘information’ is beside the point. What counts is what the DNA means, not how big it is. And meaning depends on context, as well as content: you can’t regulate the temperature of a uterus unless your context (that is, mother) provides one.
The simple-minded ‘mutation’ viewpoint, allied to trendy interpretations of DNA function in terms of ‘information theory’, is often allied with ignorance of biology in other areas. One example is radiation biology and simple ecology as seen by ‘conservation activists’. Some of these volunteers found five-legged frogs and other ‘monsters’ downwind of the Chernobyl site, years after the nuclear accident but while radiation levels were still noticeably high. They claimed that the monsters were mutants, caused by the radiation. Other workers, however, then found just as many supposed mutants upwind of the reactor site.
It turned out that the best explanation had nothing to do with mutant frogs. It was the absence of their usual predators, owls and hawks and snakes, because there were so many humans trudging about. Rana palustris tadpoles from Chernobyl produced no more of these pathologies than did other frogspawn samples from ponds some tens of kilometres away that had not been subjected to radiation, when a high percentage of both was allowed to survive. Usually, in British Rana temporaria frogs, it is very difficult to achieve ten per cent normal adults, or even ones that are viable in the laboratory, but they don’t produce extra limbs as palustris does. It is normally the case, of course, that a female frog’s lifetime production of some 10,000 eggs results in a few highly selected, and therefore ‘normal’, survivors, and on average just two breeders. But conservationists don’t like thinking about this reproductive arithmet
ic, with all those deaths.
Here is another issue, again chosen from the thalidomide literature, that demonstrates how talk of Lamarckism, or of ‘mutations’, misses the point.
Some of the children affected by thalidomide have married each other, and several of these pairings have produced phocomelic children. The obvious deduction, from the folk-DNA point of view, is that the DNA of the first generation must have been altered, so that it produced the same effect in the next generation. In fact, this effect looks, at first glance, like Lamarckism: the inheritance of acquired characters. Indeed, it seems a classic demonstration of such inheritance, as convincing as if cutting off terriers’ tails resulted in puppies being born with short tails. However, it is actually a lesson in not attempting to explain things ‘at first glance’, like the conservationists did with the abnormal frogs.
It is very tempting to do just that, when the idea of heredity in your mind is that one gene leads to one character, so if you’ve got the character you’ve got the gene, and vice versa. Figures from the epidemiological literature suggest that in the space of a few years either side of 1960, about 4 million women took thalidomide at the critical time during gestation. Of those, about 15,000–18,000 fetuses were damaged; 12,000 came to birth with defects, and about 8,000 survived their first year. That is to say, the natural course of development selected just 1 in 500 who showed adverse effects. The proportion of children born with no detectable defect was much, much higher. And that fact changes our view of the likely reason for the children of two thalidomide parents to suffer from phocomelia, for the following reason.
Conrad Waddington demonstrated a phenomenon called ‘genetic assimilation’. He started with a genetically diverse population of wild fruit flies, and found that about one in 15,000 of their pupae, when warmed, produced a fly with no cross-vein in its wing. These ‘cross-veinless’ flies looked just like some very rare mutant flies that turned up occasionally in the wild, just as occasional genetically phocomelic children turned up before thalidomide. By breeding from the flies that responded to the treatment, Waddington selected for a lower and lower threshold of response. In a few tens of generations, he had selected flies that bred true for the cross-veinless trait, exhibiting it regularly without anyone warming the pupae. This may look like Lamarckian inheritance, but it’s not. It’s genetic assimilation. The experiments were selecting flies that had no cross-vein at lower and lower temperature thresholds. Eventually, they selected flies that had no cross-vein at ‘normal’ temperatures.
Science of Discworld III Page 27