Four old news items on genetics and phylogeny

To see the past The present is the consequence and, if you like, the hostage of the past. Looking around, we see facts but do not understand their causes, hidden in the past. Unfortunately, the past cannot be observed — it can only be reconstructed. It is well enough if the traces of former facts have only been distorted, having been under the heel of destructive time. The overwhelming part of the events of the past is simply erased without a trace. Laplace's all-knowing demon, the expression of the classical faith in the power of science, could, from the position and characteristics of the motion of all existing particles, fully compute the prehistory and posthistory of the Universe. Now we have realized the frightening indeterminacy of the future, hidden behind the terms "deterministic chaos", "strange attractor", "Heisenberg uncertainty" and other incantations. With the past it is no easier. Since the present is not unambiguously determined by its prehistory, the observed present may correspond to an infinite multitude of potential pasts that determine it by their properties! Any development is a conflict between memory (the preservation of a system's properties) and change (the adaptation of this system or its destruction). He who has acquired much has also forgotten much… Forgive me, I have dragged out the turn to the example of reconstructing the past that I will tell about. It concerns the emergence of vertebrates onto land. It is hard to realize how different the conditions for the life of large animals are in water and on land. How did our ancestors cross this boundary? A happy accident? Probably not. Such a transition apparently occurred independently in several evolutionary branches of fish, which gave rise to several groups of the first tetrapods! The adaptations of fish to life in the shallow water bodies of the Devonian period proved to be the key to the mastery of land. Without going into details, I will note that limbs arose as an organ for pushing off the bottom in shallow water, and lungs — as an organ for breathing air when the head is above the surface of the water. It is good that we have evidence of the structure of the limbs in several half-fish, half-tetrapods. But how were the other systems rebuilt? One can glimpse the past with the help of models. Researchers from the Swiss Federal Institute of Technology in Lausanne (EPFL) built a model of the first tetrapods. The body is a chain of nine movable blocks; on the second and sixth are legs1. The "nervous system" is arranged by analogy with the nervous system of a lamprey2. Such a construction, despite the primitiveness of the nervous system, can not only swim but also crawl. Interesting, only it's a pity that these experiments have practically no relation to the real past. Another work uses the means of genetics. Nature published an article by Marcus Davis and co-authors from the University of Chicago. The authors studied Hox genes — the switches responsible for forming the body plan. The expression of the Hox genes responsible for forming limbs in tetrapods goes through two phases. The first is connected with the formation of the limb or fin itself, the second — with the formation of the digits. In tetrapods both phases are recorded; in the zebrafish (an aquarium fish) — only the first. The authors of the work studied the paddlefish, an American representative of the sturgeons, and found in it both the first and the second phase of the expression of such genes. Well, an interesting fact. But the conclusion drawn from it is dubious: the scientists believe that the development of limbs in ancient fish was predetermined, "stitched into" their genes in advance. The paddlefish is in approximately the same relationship with tetrapods as the zebrafish — tetrapods descend from another group of fish, the lobe-finned. The presence of similar gene sequences in no way indicates a similarity of functions: they can be reassigned. An analogy: the bones located in the middle ear of humans and other mammals (the malleus and incus) descend from the bones that formed the jaw joint in our reptilian ancestors. Does this mean that the plan of the mammalian middle ear is "stitched" into the jaws of reptiles? No! When the former functions of these bones proved lost, they acquired new ones. And can one then assert that the genes which performed certain functions in ancient fish contained the plan of the functions they began to perform in tetrapods? So, was there no determinacy in the mastery of land? Who knows… The fact that it is not proven in Davis's work does not mean that it did not exist. One example. There is a fish, the mudskipper (which, by the way, is a relative of the zebrafish rather than the paddlefish, and most likely lacks the second phase of Hox-gene expression of the limbs). In 1934 J. W. Harms showed that on the introduction of the hormone thyroxine3 the pectoral fins of the mudskipper turn into something like limbs, thin little paws.

Did determinacy concern the pathways of rebuilding ontogeny?

And can one reconstruct the past at all by studying modern living systems, which became what they are only because they forgot a substantial part of their past?

Though we are hostages of the past, it is not given to us to know precisely what, and how, determines our fate. So we express only conjectures… 1 Not at all like the legs of the first tetrapods… Back to the text 2 Why lampreys in particular? Is it related to the first tetrapods? Well, in some sense we are all relatives, but the lamprey is farther from the modelled animals than, for example, fish are… Back to the text 3 A hormone that triggers maturation and emergence onto land in amphibian larvae. Back to the text Marsupial interest Several recent news items have a direct bearing on marsupial mammals. The genome of the first marsupial — the gray short-tailed opossum, Monodelphis domestica — has been decoded. In Brazil this little animal lives in dwellings, like a mouse, but feeds not on human stores, but on rodents and insects (a predator, after all). One of the first conclusions of the study of this animal's genome is that the evolution of placentals ("our" group of mammals) was connected not with the appearance of new proteins, but with a change in the mechanisms regulating development (to someone this was unclear without special studies). The studied species is interesting for medicine too. In it, as in humans, ultraviolet can cause melanoma, and besides, its young astonish physicians with their ability to recover after severe spinal-cord injuries. In general, the young of marsupials are one of the marvels of nature. How many generations of biologists have wondered how a tiny, underdeveloped embryo, immediately after birth, is able to overcome the path to the maternal nipple! One of the interesting consequences of early birth is the powerful protective properties of the maternal milk. The newborn's immune system is not yet formed, and it would be an ideal nutrient medium for bacteria, were it not for the antibiotics of the milk. Australian biologists are now studying the protective substances in the milk of the tammar wallaby (a kangaroo of that species), Macropus eugenii. One of these substances has already been synthesized, and it has proven a high ability to destroy bacteria (and not merely to stop their growth, as most antibiotics do). And did you know that female marsupials have two vaginas and two uterine horns, and males, correspondingly, paired or forked genital organs? This is, of course, an archaic feature. But the fact that the mass of the young does not exceed 0.2% of the mother's body mass is not so bad. Compare the birth of a kangaroo, for example, with the feat of a fifty-kilogram woman in labour giving birth to a newborn weighing three and a half kilograms! But there is one circumstance that is sad for marsupials. Their brain must very early begin to control the young's life activity: it must crawl to the nipple, hold on to it, digest the available food… The marsupial brain has no such luxurious interval of embryonic growth "for the future" as the placentals have, and this is a serious shortcoming. Romantics still search in the hard-to-pass forests of Tasmania for the marsupial wolf. The largest of the marsupial species that survived until the coming of humans was destroyed not only by hunters but also by feral dogs. By its technical characteristics the marsupial wolf surpassed the dingo in all respects, except one — flexibility of behaviour. Dogs are able to coordinate their actions in a pack and to predict the behaviour of their prey. Since their prey were marsupials, and all marsupials, alas, are dim-witted compared to placentals, everything worked out well for the dogs. But the Tasmanian wolves were left without food and disappeared. …No, the fact that of two parallel branches of evolution it was the line of placentals, not marsupials, that led to us, is not accidental. But this is no reason to treat marsupials without respect! The evolutionary rut In recent years the hypothesis of the parallelism of key evolutionary events has gained ever more confirmation. The formation of a new group occurs in many evolutionary branches that pass through similar stages. This process is conventionally called "-ation" (mammals arose as a result of the mammalization of mammal-like reptiles, birds — as a result of the ornithization of dinosaurs and their relatives, tetrapods — of the tetrapodization of lobe-finned fish, flowering plants — of the angiospermization of gymnosperms, and so on). How is one to study the foundations of this process experimentally? We have no model biosphere with accelerated time, and we must make do with the biochemical evolution of bacteria. Besides their theoretical significance, bacterial models also have practical significance, allowing, for example, the study of the dynamics of the development of resistance to antibiotics. In such experiments a harsh selection of bacteria for resistance to an influence that requires the change of several genes is used. As we recently wrote (see "CT" No. 637), simultaneous selection for many genes is ineffective, so the genetic changes of bacteria are arranged "in a chain". First one mutation occurs that increases resistance. After its spread through the population, the fixing of a second mutation becomes probable, and so it continues until the final state is reached. Of course, for this it is necessary that the sequence of mutations be able to line up in a chain in which, at each successive stage, the bacteria are better adapted to the changed environment. At Harvard University the development of bacterial resistance to the antibiotic cefotaxime was studied. To defend against it, bacteria need five substitutions in the gene of the enzyme beta-lactamase. The appearance of five mutations at once is incredible, and the evolving bacteria must pass through at least four intermediate states (the first mutation of five, the second, and so on). The number of trajectories that do not envisage backward movement is 5!=120, and the number of possible intermediate states is thirty. With the help of genetic engineering all thirty intermediate enzymes were constructed. For each of the enzymes the antibiotic resistance of the bacteria possessing it was measured. Of the one hundred twenty trajectories, one hundred and two require a decrease of fitness and are discarded. The most successful are two possible paths. According to the calculations, 50% of all evolving lines of bacteria should pass along these paths. Another 49% use eight less successful trajectories, and along the remaining eight biochemical paths only 1% of bacterial groups will pass. Researchers from Rice University in Houston tried to track the process of transformation "live" and chose bacteria from hot springs. The wild type of Geobacillus stearothermophilus lives at 73 °C. The experimenters used a mutant line that had lost its thermostability, and grew it in ever-hotter water, so that the bacteria had to restore the damaged gene. The first step was a mutation allowing them to withstand a temperature of 62 °C; after it five modifications appeared, of which two proved more stable than the others. Unfortunately, the wild type could not be restored. But, repeating the experiment, the researchers obtained the same stages of evolution of the experimental population. It seems it has been possible to prove that the biochemical evolution of bacteria proceeds along an established path. But note: in both cases the development of an already existing trait was modelled. This concerns both the (as a result of our activity) widely spread resistance to antibiotics and the natural thermophily of the inhabitants of hot springs. But in the cases of the "-ations" with which we began, something fundamentally different arises, which cannot be explained by point mutations lined up in a chain. The more interesting it is to learn that canalization is predetermined even at the molecular level. On the length of the snout As knowledge of the functioning of the genome expands, it becomes ever clearer that evolutionary changes of an organism are connected not with the appearance or destruction of new genes, but with a change in the activity of already existing regulatory mechanisms. Often evolutionary changes manifest only in an increase or decrease of the relative growth rate of one or another part of the body. Take, for example, the chin protrusion. As modern humans formed, their chin became ever larger and more pronounced. What is this organ for? It is natural to assume that it is somehow connected with speech. However, studies of articulation in people on whose chin you could hang a kettle, as well as in those with a receding lower jaw, showed that these features do not affect command of speech. Everything becomes clearer if one takes into account how human development occurred. Our skull consists of two parts: the facial and the cerebral. To accommodate the large brain, it was necessary to accelerate the development of the cerebral part and slow the development of the facial. The lower jaw consists of two relatively independent blocks: the dental and the supporting. The growth of the dental part proved slowed more strongly, and the part that grew faster "stuck out" forward, forming the chin. It turns out that the chin is not an organ (a part of the body performing a certain function), but a by-product reflecting our evolutionary unfinishednesses. And what modifications of the genome ensure such changes? The results obtained at the UT Southwestern Medical Center in Dallas will help answer this question. Here characteristic genetic sequences in various breeds of dogs were studied. The researchers noted a correlation between the length of dogs' snouts and the character of the so-called tandem repeats (multiple copies of identical sequences located one after another and oriented, unlike palindromic sequences, in one direction). A diversity of tandem repeats was recorded in wild representatives of the dog family too, but it is much smaller than in domestic ones. Apparently the rapid evolution of breeds was made possible thanks to rearrangements of the highly variable part of the genome, to which the tandem sequences belong. The reports of the obtained results that went through the news agencies, like the researchers' own accounts, reflect one and the same illusion. The authors of the discovery decided that they had described not the mechanism, but the cause of the evolutionary changes. (This testifies to the unwillingness of molecular specialists, the "biological elite", to spend effort on acquainting themselves with the current state of evolutionary doctrine; they are satisfied with the synthetic theory of evolution that appeared in the 1940s.) How did dog breeds appear? People kept those breeders who possessed the qualities interesting to them. For example, long-legged, long-snouted dogs are good for hunting hares. In selecting such individuals, all the features of the genotype that increase the probability of development in the desired direction were preferentially preserved; rearrangements of tandem repeats were among them. Is, for example, the lengthening of the snout connected with them? There are no grounds to assert this. By the way, experiments on selection in a particular direction show that one and the same external effect can be achieved through different genetic changes. Can such changes be considered the cause of the observed traits? No, this is merely one of the mechanisms of their manifestation. For example, the fact that the cellulose fibres of paper are wetted by printing ink is a mechanism that allows you to read these words, but by no means their cause. By the way, the main differences between the genomes of humans and chimpanzees also concern highly repetitive sequences. Well, our snout was shortening too… D. Shabanov. To see the past // Computerra, Moscow, 2007. — No. 24 (692) D. Shabanov. Marsupial interest // Computerra, Moscow, 2007. — No. 19 (687) D. Shabanov. The evolutionary rut // Computerra, Moscow, 2006. — No. 22 (642) D. Shabanov. On the length of the snout // Computerra, Moscow, 2005. — No. 4 (576). — pp. 14–15