Genetics of Original Sin

by Christian De Duve

  As far as I know, model A represents the generally held view. Its shape corresponds to that most often given in treatises for the human “tree” or “bush” (shown here lying down). Model B, first proposed in 2005 in my book Singularities, has not, to my knowledge, been considered before. I tend to favor it because it assumes a single genetic propensity toward bigger brains, with a number of stops on the way, whereas, in model A, a new drive toward brain expansion is initiated at each level. Model B is thus the more economical of the two in terms of the number of required genetic changes. This could be a point in its favor. Indeed, an impressive aspect of hominization is the extraordinarily small number of individuals involved at any stage, as opposed to the importance of the changes that characterize the process.

  Fig. 10.3. Two models of human brain expansion. These two models are drawn using data from fig. 10.2. (A) Model based on the hypo thesis that jumps from one level to the other occurred as late as the data permit. (B) Model based on the hypothesis that all levels extend laterally from a single ascending curve. Note that stone tools started to be manufactured by creatures with brains half the size of the modern human brain. Model B adapted from Christian de Duve, Singularities (New York: Cambridge University Press, 2005), 222.

  We saw in chapter 9 that the group, comprising mitochondrial Eve and Y Adam, ancestral to the entire, present-day human population may have included no more than ten thousand individuals. Studies of the Neanderthal genome have suggested an even smaller number—on the order of three thousand—for the common ancestral population from which Neanderthals and Cro-Magnons diverged more than half a million years ago. That the appropriate genetic change could have taken place at each stage in such small populations is flabbergasting. It indicates that the changes must have been either exceedingly probable or very few in number. The latter condition is better fulfilled by model B of figure 10.3, but the argument is not decisive. A single tendency toward expansion that was repeatedly stifled and reawakened could account for model A.

  We must leave it to the experts to decide which of the two models—or any model intermediate between the two—is more likely to be the correct one. What I wish to examine here is the manner in which the “jumps” from one level to another took place, whether in one or the other model. In my graphs, rather than connecting the levels by abrupt steps, in staircase fashion, I have rounded the angles to give S-shaped, or sigmoid, curves, which seem to me more realistic.

  Mathematicians have long been familiar with this type of curve, known as the logistic curve. It reflects two opposed phenomena: one, an exponential increase such that every increment enhances the rate of the following one; and two, a braking effect that increasingly slows down the process as it progresses, until it stops at a limit value that generates an unchanging plateau. What natural processes could account for these two phenomena in the case of brain expansion? Figure 10.4 illustrates a possible answer to this question.

  Fig. 10.4. Logistic curve, as applied to the expansion of the human brain in the course of evolution. The curve combines an exponential increase with a braking effect. The exponential part is attributed to neuronal multiplication and the braking effect to anatomical constraints, either the size of the fetal cranium or that of the female pelvis, or both.

  Exponential neuron multiplication braked by anatomical constraints probably explains the sigmoid shape of the jumps of brain volume from one plateau to another

  For biologists, cell division is the iconic example of an exponential process. One cell divides into two, which divide into four, which divide into eight, sixteen, and so on. Cell division happens also to be the indispensable mechanism behind brain expansion. One is thus naturally led to the hypothesis that the exponential rise from a lower to a higher level reflects cell division. This assumption is particularly attractive, as it ascribes all the successive rises to a single phenomenon.

  The simplest factor that could account for the braking effect responsible for causing the plateau is some kind of anatomical constraint. Here, several factors may come into play. First, there is cranial capacity. As the brain enlarges, it is increasingly hindered by its bony box. This leaves two possibilities. The cranium does not yield, so that only individuals in which neuronal division is genetically programmed to stop at a certain stage are allowed to survive and produce similarly programmed progeny, accounting for the plateau. Or the cranium yields to the outward pressure exerted by an expanding brain, a distinct possibility as the cranium is made of a number of plates that, in the fetus and even in the newborn, are linked by membranous connections that could indeed stretch, as required. If this happens, the drive toward a bigger brain is allowed to proceed further, until a new obstacle is encountered, generating the next plateau. A second factor that could increasingly limit brain size, as it expands, is the dimension of the female pelvis, which may oppose the birth of young with bigger heads. A possible way of overcoming this kind of obstacle would be by way of a change in the brain’s developmental program, so that the brain achieves a lesser degree of maturity in the womb and completes a greater part of its maturation after birth.

  Expansion of the human brain was limited by the size of the female pelvis and by the degree of immaturity at birth compatible with survival

  There are clear indications that all three factors have played a role. Cranial capacity has obviously increased. Except for humans and chimpanzees, the brain volumes in figures 10.2 and 10.3 are all derived from cranial measurements. On the other hand, the female pelvis, although it may have adapted in some measure to this change, has apparently offered considerable resistance to the birth of babies with bigger brains, with, as a consequence increased immaturity at birth, or neoteny. This is a typical human feature.

  Delivery in humans is excruciatingly painful, probably at the limit of what is bearable, whereas it seems to cause relatively little discomfort in other mammals. Development of the human brain inside the womb obviously takes place until the size of the head has reached the utmost limit compatible with passage through the birth canal. Even so, the brain is still at a very immature stage and continues to undergo outside the womb a developmental process that, in other mammals, is largely completed in utero. A human baby is entirely helpless at birth and will need many months to reach a stage where it can match the autonomy of, for example, a newborn foal. In all appearance, natural selection has, in humans, favored birth at an increasingly immature stage as the price to pay for a better brain. This brings us to the history of our genes, the subject of the next chapter.

  11

  Shaping Our Genes

  We are, like the rest of the living world, largely products of natural selection. Our genes are there because, at some stage in evolution, they happened to be useful to the survival and reproduction of their owners or, at least, were not sufficiently harmful for their owners to be eliminated. Some 98.5 percent of those genes existed in the last ancestor we have in common with chimpanzees and were gained at some stage in the long pathway that led from the first forms of life present on Earth more than three and a half billion years ago to the last bifurcation that separated the hominid primate branch from the chimpanzee branch, some seven million years ago. Those genes account for all the properties we share with chimpanzees. We owe what makes us specifically human to the remaining 1.5 percent. It sounds little, but it is still a lot, a genetic text of about forty-five million “letters,” a pretty fat book.

  Hominization involved an astonishingly small number of individuals

  In trying to identify those genes and to explain their selection, we immediately encounter a challenging difficulty. The number of individuals involved at any stage of hominization must have been very small, probably never exceeding a few thousand, if that many. A wide range of mutations is not expected to occur at any time in such a limited population, and the probability that an appropriate mutation will be included in the lot is correspondingly reduced. Thus, assuming an average lifetime of twenty years and a total population of five thousa
nd, the number of new births and, therefore, the number of genetic variants offered to natural selection would be on the order of 250 per year, which appears very small. This number is, however, no longer insignificant if duration is taken into account. Over fifty millennia, for instance, which is less than one-hundredth the total time taken by the hominization process, the number of variants exceeds ten million.

  Also important, the population was probably divided into small bands of some thirty to fifty members, closely inbred and related by kin. In such a situation, whatever favorable mutation was offered had a good chance of being efficiently exploited, as it would quickly spread within the group and provide its members with an edge over other groups that did not enjoy the same advantage. We shall see the key importance of this feature.

  The fact remains that the chances of evolutionary success were bound to be greater if favorable mutations had a high probability of taking place and if the number of required mutations was small. It is interesting, in this respect, that some of the main differences that have been found between the human and chimpanzee genomes affect genes that influence other genes by way of transcription regulation (see chapter 6). Thus, changes in only a few such master genes could have had wide-ranging effects. Also suggestive, in relation to brain expansion, is the observation from human pathology that brain size may be controlled by very few genes. Two kinds of inborn microcephaly (small brain) have been traced to the mutation of a single gene.

  Let us now look at the long pathway of hominization within the framework of natural selection. This pathway may be divided in very approximate fashion into three successive stages, involving different genetic changes and selective factors (see figs. 10.2 and 10.3).

  Hominization probably started with bipedalism, which was selectively advantageous in the local terrain

  First, until about three million year ago, the main element was the conversion from quadrupedalism to bipedalism, accompanied by only a moderate increase in brain size. Then, covering the next million years, comes a period of rapid brain expansion, associated with the making of stone tools of increasing sophistication. Coming finally are the great migrations out of Africa, which took place in two waves: one, starting some two million years ago and invariably ending in extinctions; the other, launched some half a million years ago and bringing forth, first, the Neanderthals, who also disappeared, and, later, the conquerors of the planet and only survivors of the adventure, Homo sapiens sapiens.

  Considering first the conversion from quadrupedalism to bipedalism, one is struck by how many anatomical changes must have accompanied this conversion. Legs became longer, arms shorter; feet became adapted to walking, hands to grasping; the spine, pelvis, and shoulders all underwent changes that facilitated an erect posture and the corresponding gait; the position of the head with respect to the rest of the body was modified; muscles, nerves, blood vessels, and viscera followed the skeleton in evolving to allow new kinds of movements and adapting to different weight distributions. The number of genes that had to be modified for all these adjustments to be achieved cannot be guessed but must have been substantial.

  Most of the changes involved, however, happened after commitment to bipedalism had already occurred; they represent improvements, added slowly over several million years, that benefited creatures that had converted to bipedalism. This conversion itself was the decisive factor. Many of our primate cousins walk on two legs intermittently or even regularly, so the final tip-over could have depended on very few genetic changes. What selective advantages may have resulted from the adoption of bipedalism is a question that has prompted much speculation and discussion. Displacement from the forest to the savannah, as assumed by the “East Side Story” (see chapter 9), may have played a significant role. Freeing the hands may have been another major advantage.

  Brain expansion dominated the second major stage of hominization

  What about the next stage of hominization, highlighted by brain expansion and tool-making? Here, an environmental explanation of natural selection seems much less probable than for the first stage. One would expect a more effective brain and more skillful hands to be selective assets under any environmental condition. Furthermore, there seems to be no reason to suspect that this stage of human evolution involved major environmental upheavals. For all we know, it could have taken place mostly under more or less unchanging conditions, in the semiarid regions of northeast Africa. Remember the traces of steps preserved in Laetoli ash during more than three million years (chapter 9).

  The dominant factor under such stable environmental conditions could have been competition among bands for the richest hunting and gathering grounds, especially if foods were scarce and difficult to come by. Competition among males for the most desirable females could have been another factor. Here we encounter what may have been a crucial stage in our history, with natural selection reinforcing in our genes two traits that were there before but became increasingly important as the ability to act purposefully improved: solidarity within groups and hostility among groups, especially manifested by males. We shall see in the following chapter to what extent this legacy still affects human behavior today.

  The vagaries of environmental change probably guided the migrations that characterized the third stage of hominization

  What caused the third stage of hominization and first drove Homo erectus and his contemporaries out of Africa, and later impelled Homo sapiens to inaugurate a new series of migrations, is not known. Search for food, perhaps in the wake of migrating herds, probably was a factor. Once the migration started, environmental challenges no doubt again played an important role in natural selection. As the migrant groups encountered different climates and milieus, different traits were retained or rejected by natural selection. We have seen, for example, how loss of pigmentation may have been favored in northern areas, where the weak UV radiation emitted by a pale sun became an asset, rather than a liability. Environmental differences may likewise account for other, less well understood changes that differentiate the major human ethnic groups. Remarkably, in spite of these changes and of long periods of isolation from each other, the different groups—the so-called human races of earlier treatises—never evolved to the point of no longer being able to interbreed. We form a single species.

  Hominization: Chance or necessity? Summit or stage?

  Looking back over the fabulous story of our origins, we can’t help asking a number of questions. Was the birth of humankind the outcome of an extraordinary combination of circumstances, of a unique conjunction between an improbable genetic accident and environmental conditions that happened by chance to be conducive to exploitation of the accident? Or, on the contrary, had the evolution of the primate brain reached a point such that only a flip was needed to trigger a process that was, so to speak, written in the genes at the time and ready to be initiated? In the latter event, what could have been the triggering flip? If it had not happened, could some other event have started things going? Last question, has the process reached a summit? Or could it continue and one day lead to “superhumans” with mental capacities distinctly superior to ours?

  We obviously have no answers to these questions. Concerning the first one, all that can be said is that the pace of hominization, as it can be quantitatively estimated from that of brain expansion (see fig. 10.3), suggests an irresistible process that, once set in motion, proceeded at a growing, almost autocatalytic rate, repeatedly overcoming the obstacles that opposed its progress. This looks more like a case of evolutionary maturity, waiting only for a triggering flip, than like an extraordinary stroke of luck, raising the question of the nature of the triggering flip. Could it have been a critical mutation of a gene controlling the size of the brain? Or an environmental accident, such as the replacement of forest by savannah assumed in the “East Side Story”? Or both? There is no way of knowing, but one is tempted to suppose that, if events had been different, the necessary triggering flip would nevertheless have occurred, so impressive is th
e apparently obligatory character of the process, once initiated.

  As to the last question, the present situation allows no prediction. One can simply say that there seems to be no objective reason for assuming that hominization has reached an unsurpassable summit. This question will be further examined below (see chapter 14).

  12

  The Cost of Success

  T hey numbered a mere three thousand about half a million years ago, in the heart of Africa, when the Neanderthals left them to go their own way. There were little more than ten thousand of them, some three hundred thousand years later, when mitochondrial Eve, Y Adam, and their congeners set off on their final stretch toward Homo sapiens sapiens; an estimated five to ten million, thinly scattered over a good part of the world, when the first durable human settlements were created ten thousand years ago. Since then, they climbed to about half a billion in 1600, one billion around 1800, two billion in the 1930s, four billion in the 1970s, and more than six and a half billion today. If nothing changes, they will exceed nine billion in 2050. The exponential increase of the human population predicted by Malthus is dramatically manifest, even exceeded (fig. 12.1).

  Fig. 12.1. Human population expansion in the last centuries. The rise has grown to hyperexponential in the last two centuries, but may be starting to slow down in recent years, initiating a logistic curve.