With the passage to land, new mechanisms were required to compensate for the lack of water. The main such mechanism for animals was copulation, which is carried out by most land animals, invertebrates as well as vertebrates. The consequence of copulation is that fertilization takes place inside the female body. At first, the ancestral mode of aqueous development prevailed. Impregnated females laid their fertilized eggs in water, where embryological development occurred. Among insects, for example, mosquitoes behave in this way, which explains their predilection for swampy environments. Other insects, as well as many other terrestrial invertebrates, have evolved a great variety of reproductive strategies. Their description is beyond the scope of this book. I shall restrict myself to the land vertebrates, which are of more direct interest to us, as the human species is one of them.
The fertilized egg of vertebrates has always developed in an aqueous medium
Amphibians, which were the first vertebrates to leave water, acted like the mosquitoes, quickly returning to their original medium for embryological development. Frogs offer a familiar example of this behavior. Females, after copulating on land, lay their eggs in water, where the eggs develop into swimming tadpoles adapted to aquatic life. Then, at some stage, signaled by the secretion of thyroid hormone, the tadpoles shed their tail, sprout two pairs of legs, lose their ability to derive oxygen from water, and start breathing air. The mature animals pursue their existence on land, but in the vicinity of water, where, eventually, females return to lay their fertilized eggs. This group of animals continues to thrive in all marshy lands.
The link with water was broken—or rather displaced from external to internal—by the reptiles, thanks to acquisition of a new structure of crucial importance, the amniotic pouch, a closed, fluid-filled sac within which fertilized eggs henceforth underwent development; they no longer needed to be laid in a body of water. Usually encased within a hard shell, the eggs could be left on land to continue their development and hatch in the open.
The reptiles bequeathed this reproductive mode to the birds and to the first mammals, the monotremes (such as the platypus), which still lay eggs. A branch then arose, in which egg-laying was replaced by birth at a very early stage of development, which was allowed to continue further within a ventral pouch, or marsupium, from which the young could reach the mammary glands to feed. Thus were born the marsupials, such as kangaroos and koalas.
The last major acquisition in this saga was the placenta, a remarkable structure that brings in intimate proximity, separated only by the thickness of blood-vessel walls, maternal blood brought in by the mother’s circulation and fetal blood conveyed via the umbilical cord, so that nourishment can pass from mother to fetus, and waste products can be unloaded from fetus to mother. Thanks to this development, which is characteristic of most of today’s mammals, including humans, development was allowed to continue inside the womb up to a sufficiently advanced stage for the young to be able to pursue an independent existence (with appropriate fostering). Note that, even in this most perfected mode of development, the fetus continues development in its ancestral, aquatic mode within the amniotic pouch. Human birth, as every mother knows, is heralded by the “breaking of the waters.”
6
Development
How, in a matter of nine months, does a fertilized egg become the miracle that is a newborn baby? This question has been asked by generations of biologists ever since William Harvey (1578–1657), the English physician who discovered blood circulation, exclaimed, after dissecting a pregnant doe felled in hunting by his patron, King Charles I: “Omnia ex ovo,” all (living beings) arise from an egg!
The first accounts of embryological development were purely descriptive
The embryologists who tackled this problem found that the fertilized egg first divides into a small number of almost identical cells, which form a cluster called the morula, the diminutive of morum, the Latin word for mulberry. These are the widely publicized stem cells, called “totipotential” because they can give rise to any cell in the body.
Soon, the morula turns into a hollow sphere, the blastula, fitted with a single opening, the blastopore, which went through a remarkable history in the course of evolution. It was mentioned in chapter 3 that the first animals to possess a digestive pouch, such as jellyfish, have only a single opening connecting the pouch to the outside and serving both for the intake of food and for the discharge of waste. Later, the pouch acquired a second opening, turning into a canal, with a mouth at one end and an anus at the other. What was not mentioned in chapter 3 is the remarkable developmental history of these openings. In the first animals with an alimentary canal and in most invertebrates that followed, including all mollusks and arthropods up to the present day, the mouth originates from the blastopore, and the anus from the newly formed opening. At some stage, however, an extraordinary developmental flip-flop initiated a new evolutionary line, with the blastopore henceforth giving rise to the anus, and the new opening becoming the mouth. This conversion from protostomes (mouth first) to deuterostomes (mouth second) initiated events of immense portent. It was followed, in the line where it occurred, by formation of a dorsal structure, or notochord, soon to be replaced by a segmented assemblage of cartilaginous units, the first vertebrae. This is how the vertebrates were born. The significance of this development could hardly be overestimated.
Starting from the blastula, a long succession of highly complex developmental changes occur, following different scripts in different species. In the human species, these steps lead—from embryo to fetus to newborn—to the progressive appearance and shaping of limbs, organs, and other body parts, up to a stage where the newly made organism is ready to leave the protective shelter of the amniotic fluid and sever its lifegiving connection (through umbilical cord and placenta) with the maternal organism and make its entrance into the outside world where oxygen is to be obtained by breathing, food by sucking, and attention by shrieking.
A remarkable aspect of this development, already noted by early observers, is that it goes through stages that recall the evolutionary history of the organism. Thus, the human embryo has gills at one stage, like fish. In the words of the German biologist and philosopher Ernst Haeckel (1834–1919), who was an enthusiastic disciple of Darwin, “ontogeny recapitulates phylogeny,” by which he meant that the developmental program of an organism recapitulates the organism’s evolutionary history, a view that is no doubt oversimplified but nevertheless proved perceptive.
Experimental embryology began to decipher developmental mechanisms
By the 1950s, this developmental script was known in exquisite detail, not only for humans, but also for chickens, fruit flies, and several other animals. But the script was known mostly in strictly descriptive fashion, with hardly any information on mechanisms, like a movie lacking a soundtrack. This was not for want of trying. In the beginning of the twentieth century, experimental embryologists, led by the German Hans Spemann (1869–1941), had succeeded, by delicate interventions, in identifying “morphogenetic gradients,” presumably created by substances, called “organizers,” secreted at one site of the embryo and diffusing toward the others. But the nature of these substances, their origin, and their mode of action were totally unknown, until, in the second half of the century, the key to the riddle was revealed almost overnight, at least in principle. The secret turned out to be: transcription control.
Development is ruled by transcriptional gene control
We have seen that the instructions stored in DNA—which include, prominently, the directives for embryological development—must be transcribed into RNA in order to be executed, most often by proteins synthesized according to the RNA transcripts. Thus, the process of transcription is the obligatory channel for gene expression. Certain protein molecules, called transcription factors, regulate this process. They turn genes on or off, that is, they induce transcription of the genes or block it. Some of these transcription factors even have a graded effect, adjusting the rate
of transcription and, thereby setting the extent to which a given gene is expressed. Transcription factors exist in the simplest of bacteria but are enormously more numerous and more important in multicellular organisms. They control the whole of embryological development.
As already seen in chapter 3, all the cells in the body have the same genome. Cells differ, becoming skin cells, nerve cells, liver cells, and so on, by transcription regulation. Turning on certain genes and shutting off others determines the fate of a given cell. This is how identical stem cells differentiate to become the 220-odd different kinds of cells that compose the human body. Thanks to the tools of modern molecular biology, we are beginning to know which genes need to be awakened or silenced in order to make a given type of cell.
This is only a small part of the story, of course. In embryological development, cells do not just differentiate into given types; they become associated in specific patterns, to form tissues and organs, which themselves become organized according to a specific blueprint or body plan. Called morphogenesis, this process is extremely complicated and still poorly understood, as it depends on mysterious signals between and among cells that are only beginning to be unraveled.
Genes are organized by transcription into a hierarchy dominated by master genes
Transcription factors are proteins, which means that they are the translation products of genes, which are themselves subjected to regulation by transcription factors produced by other genes, and so on. There thus exists a hierarchy of genes, which is dominated by “supergenes” that act as master switches for entire developmental programs.
An example is the eyeless gene, so named, in the quirky nomenclature devised by geneticists, because it was discovered through a mutation that causes inborn blindness. The gene itself is responsible for the opposite of eyelessness; it controls the complete genetic program of eye formation throughout the animal world. If the eyeless gene from fruit flies is injected somewhere in the body of a fruit fly, it induces the formation of a complete, multifaceted fruit fly eye at the site of injection. If injected into a mouse, the same gene will induce the formation of a typical mouse eye at the site of injection. Conversely the mouse eyeless gene induces the formation of a mouse eye in a mouse, but of a fruit fly eye in a fruit fly. It is a universal switch. The machinery it sets off depends on the local genome.
Homeotic genes are master genes of central importance
Among the most important master genes are the genes called homeotic, which control complex developmental programs that may affect the entire body. These genes share a sequence of 180 bases, called the homeobox, which is highly conserved throughout the animal world and even in plants and fungi. This sequence codes for a stretch of sixty amino acids (the building blocks of proteins) whereby the corresponding protein binds to DNA, a prerequisite for its ability to act as a transcription switch.
In primitive animals, there is a single set of homeogenes, which command the development of the body plan. In segmented animals (see chapter 3), there are as many sets of homeogenes as there are segments, aligned along the chromosomal DNA in the order in which the segments follow each other in the body. In simple annelids, such as earthworms, the homeogenes are almost all the same and the segments they control are all identical, except for minor changes in the head and tail. With increasing diversification, each set of homeogenes has evolved on its own to produce increasingly different segments. Like the eyeless gene, such homeogenes induce the formation of the kind of segment they code for wherever they end up in the body. This is how investigators working on the fruit fly Drosophila, the central object of classical genetic research, have been able, by a single manipulation, to create freaks such as headless, two-tailed flies, animals with an extra pair of legs or wings, or strange monsters sporting legs in front of their heads in place of antennae.
Evolution and development are intimately linked
Note how evolution and development meet in these phenomena. Repetition and differentiation of homeogenes started as an evolutionary phenomenon, which later became inscribed into the developmental program. Often designated by the acronym “evo-devo,” this concatenation of evolution with development was summed up in Haeckel’s famous aphorism, “ontogeny recapitulates phylogeny,” quoted above.
The discovery of master genes has illuminated a number of evolutionary events of dramatic suddenness. We have already encountered segmentation, one of the most fateful changes in the evolution of animals. Another epoch-making genetic jump, so far unidentified but most likely involving a master gene, is the protostome-deuterostome flip-flop that initiated the line leading to vertebrates (see above).
Incidentally, the history of homeogenes illustrates one of evolution’s favorite “tricks”: gene duplication, which we have seen in the preceding chapter allows one copy of a gene to evolve while the other copy continues exercising its function. The whole history of life is landmarked, from its very beginning, with gene duplications, which lie behind countless evolutionary innovations.
In summary, we are still far from knowing how a fertilized egg produces this miracle that is a newborn baby and maybe never will, considering the awesome complexity of the underlying programs. But, at least, we know the key to the riddle. It lies in the hierarchy of gene-transcription mechanisms.
7
Natural Selection
Charles Darwin (1809–1882), who is often credited for having discovered evolution, was not even born when the transformist hypothesis was first formulated by his grandfather and by Lamarck. What Erasmus Darwin’s grandson will forever be remembered for is his proposal that natural selection of hereditary variants is the mechanism by which evolution occurs. Natural selection, contrary to evolution, which is an undisputable fact, may still be viewed as a theory, at least to the extent that it may not be the only mechanism involved in evolution, as we shall see in the next chapter. The actual occurrence and overwhelming importance of natural selection are no longer in doubt.
Unfortunately, evolution and natural selection have become conflated into the single term Darwinism. There is a historical reason for this conflation. The two notions were simultaneously defended in Darwin’s major opus, published in 1859 under the ambivalent title On the Origin of Species by Natural Selection. In the uproar that followed, Darwin was attacked more for defending evolution, a shocking theory that negated biblical truth and downgraded man to the status of mere animal. His account of natural selection as the basic mechanism of evolution was merely an aggravating circumstance that denied any intervention by God in what was assumed to be a godless process in any case. This confusion has persisted until today, fueling much of the current controversies over evolution. In this and the following chapter, I shall try to clarify the issue.
At the start lies heredity
As a starting point, consider heredity. This phenomenon was known to Darwin and to countless generations before him. Mice beget mice, acorns oak trees, humans babies. The phenomenon goes even further. Children resemble their parents more than they resemble the parents of other children. Today, we know why that is so. Individual blueprints are encoded in DNA, and these blueprints are transmitted from generation to generation by DNA replication. Darwin did not know this. He did not even know the laws of heredity, first formulated in 1866 by an obscure Austrian monk, Gregor Mendel, and appreciated by the scientific community only after Mendel’s death in 1884.
Artificial selection exploits the imperfections of heredity for defined purposes
What was known to Darwin, however, and made a strong impression on him, is that heredity is not perfectly faithful; it allows for diversity, a natural circumstance that has been exploited ever since humans started domesticating plants and animals. Look at dogs. The American Kennel Club recognizes 173 breeds. All are dogs; they recognize each other as such, communicate by the mysterious signals particular to their species, and interbreed to give viable offspring. This diversity is human-made. At the start, there was a single variety of wolf or jackal that esta
blished some kind of mutually beneficial association with a human group. From then on, breeders created all the existing varieties artificially, using empirically devised methods based on selection of appropriate progenitors. This history, which was repeated with horses, cattle, chickens, cats, and other domestic animals, as well as with a number of plants, goes back to early days of human development prior to any written record.
Today, we know the cause of diversity. It is due to modifications, or mutations, in the DNA, such that a slightly altered blueprint is transmitted from parent to offspring. This, again, was totally unknown to Darwin. But he was keenly aware of the existence of diversity in the living world and of its role in allowing breeders to use artificial selection in an empirically purposeful manner to generate cows that gave more milk, sheep that yielded thicker wool or better meat, horses that ran faster or carried heavier loads, cereals more resistant to cold or drought, and so on.
Malthus introduced the notion of the “struggle for life”
Genetics of Original Sin Page 8
