Über die Autorin bzw. den Autor

Luigi Luca Cavalli-Sforza was born in Genoa in 1922 and has taught at the Universities of Cambridge, Parma, and Pavia. He is currently Professor Emeritus of Genetics at Stanford University and is the author of The History and Geography of Human Genes.

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Genes, Peoples, and Languages

University of California Press

Chapter One

Genes and History

The Pride of an Emperor

Dante Alighieri's reputation as the grand master of Italian literaturehas eclipsed all the Italian poets and writers who followed him.Nevertheless, Dante was not the only great Italian poet. Therewere others, such as Petrarch, Ariosto, and Leopardi. The latter isperhaps the least well-known outside Italy, although he was notonly a talented poet but also a remarkable philosopher

    I recently reread his play Copernicus, which I still find relevantand insightful. The characters include the Sun, the First and LastHours of the Day, and Copernicus. In the opening scene, the Sun confidesto the First Hour that he is tired of revolving around the Eartheach day, and demands that the Earth shoulder some of the burden.The First Hour, alarmed by this prospect, points out that the Sun'sretirement would create havoc. But the Sun is adamant and insists oninforming Earth's philosophers of the impending change since hebelieves they can convince humans of anything?good or bad. Bythe second scene, the Sun has delivered on his threat. Copernicus,surprised by the Sun's failure to rise, sets about investigating the cause.His search quickly ends when he and the Last Hour are summonedto hear the Sun's proposal: the Earth must renounce her position atthe center of the Universe and instead revolve around the Sun. Copernicusnotes that even philosophers would have difficulty convincingthe Earth of that. Moreover, the Earth and her inhabitants havegrown accustomed to their position at the center of the Universe andhave developed the "pride of an emperor." A change of such magnitudewould have not only physical but also social and philosophicalconsequences. The most basic assumptions about human life wouldbe overturned. But the Sun is insistent that life will go on, that all thebarons, dukes, and emperors will continue to believe in their importance,and that their power won't be weakened in the least. Copernicusoffers further objections: a galactic revolution could begin?theother planets may assert that they want the same rights to centrality asthe Earth had. Even the stars would protest. In the end, the Sun mightlose all importance and be forced to find another orbit. But the Sundesires only rest and counters Copernicus's final fear?that he will beburned as a heretic?by telling him he can avoid such a fate by dedicatinghis book to the Pope.

    In writing about Copernicus, Leopardi had the benefit of livingseveral centuries after him. He knew what had happened to Copernicus,Giordano Bruno, and Galileo. But we do not have Leopardi'sadvantage when considering the scientific issues of our day. Anycurrent theories may be modified or even destroyed at any moment.In fact, science progresses because every hypothesis can be confirmedor rejected by others. The great number of conditionals weuse in our scientific prose underscore this truth. While correctingthe translation of one of my books, I was terrified to see that all myconditionals had been changed to indicatives?my safeguards hadbeen eliminated. When we write papers for scientific journals, weknow that many statements cannot be supported in their entirety.This seems strange to the public: isn't science infallible? In the end,only religion claims to deliver certainty. In other words, faith aloneis immune from doubt, although few believers seem troubled bythe fact that each religion offers different answers. Mathematicsmay be the only exception in the sciences that leaves no room forskepticism. But, if mathematical results are exact as no empirical lawcould ever be, philosophers have discovered they are not absolutelynovel?instead, they are tautological.

Copernicus also reminded me of our attitudes about race andracism. Each population believes that it is the best in the world.With few exceptions, people love the microcosm into which theyare born and don't want to leave it. For Whites, the greatest civilizationis European; the best race is White (French in France and Englishin England). But what do the Chinese think? And theJapanese? Wouldn't most of today's recent immigrants return totheir country if they could find a decent way of life there?

    It is also true, as Leopardi observed, that the more things change,the more they stay the same. Noble or economically powerful familiescome and go?there is an increasingly rapid turnover of power?butpower structures change very little. The Roman Empire lastedlonger than many others in Europe, but it spanned only five centuries.It was similar in size to the Inca Empire, which lasted a littlemore than a century. Before the Roman Empire, several maritimepowers?the Greeks, Phoenicians, and Carthaginians?colonized theMediterranean coast. At the same time, the European interior sawCeltic princes establish control over most of Europe. During the secondhalf of the first millennium B.C., the Celtic and maritime fiefdomswere each united by commercial, linguistic, and cultural ties,but were politically fragmented.

    Ultimately, they would all fall to the Romans. The Romans builtthe first politically united culture in Europe, but it eventually fellto "barbarian" invaders from the East. The barbarians flourished,and only the eastern part of the Roman Empire?the ByzantineEmpire?was to survive into the Middle Ages. In the west, Charlemagnefounded the Holy Roman Empire in A.D. 800, the culminationof Frankish political development. France, Germany, and partsof Italy and Spain were briefly reunited. After A.D. 1000, Frankishpower passed to Germany and, in part, to the Pope, although thePapacy and the Empire were often in conflict. The Holy RomanEmpire ceased to have any political importance by the fourteenthcentury, although Austrian emperors continued to take the title ofHoly Roman Emperor until 1806. Several European states wereformed or consolidated between 1000 and 1500. Although warsamong them were frequent, none was able to conquer much ofEurope before Napoleon. With the development of seaworthyships, the armies and navies of Europeans attempted to extendtheir hegemony to the rest of the world, competing for nationalriches on other continents. The Portuguese, Spanish, English,Dutch, French, and Russians established overseas empires whichwould endure into the twentieth century, but in all of European history,not a single empire has lasted for more than five centuries.Napoleon rapidly conquered continental Europe, but his rulelasted for fewer than ten years.

    The Chinese Empire began in the third century B.C. andendured many vicissitudes under myriad dynasties, none of whichlasted for more than four centuries. After several difficult periods,China fell to the Mongols in the thirteenth century. One hundredyears later, the Ming restored Chinese dominance for three centuries.Then another foreign dynasty, the Qing, ruled for severalcenturies into the twentieth. The same pattern is found on everycontinent or subcontinent.

    National pride is always more fervent in successful times. When apeople feels strong, it is easier to say, "We are the best." However,power can have rather unusual origins. The wise decisions andshrewd political acts of a few leaders or small groups often produceenduring states. Even cruel regimes can sometimes succeed in introducingprosperous periods. The rise to political power frequentlyrequires violence, which is not always physical. Favorable externalcircumstances can also help maintain stability, if only temporarily.Politicians who wield their power responsibly are difficult to replacewith equally capable successors. During happy and prosperous years,people can convince themselves that their success is due to theirexcellent qualities, the intrinsic characteristics of their "race" thatmake them great. The illusion of immortality ignores all the lessonsof history. The self-critic is rare and tends to be absent or has no listenerswhen things are going well.

    Perhaps Claude Lévi-Strauss most succinctly defined racism asthe belief that one race (usually, though not always, one's own) isbiologically superior?that superior genes, chromosomes, DNAput it at an advantage over all others. This is America's situationnow. It is no coincidence that you must first dial the number onewhen calling the United States from abroad.

    At any particular moment, a single people may be dominantdespite the many countries that have been before, or will be soon. Ofcourse, it is not necessary to be superior to be convinced that oneis. Even a limited success can demonstrate power to others. Manybelieve such dominance is determined by biology.

Other Sources of Racism

Almost any society can find a good reason to consider itself predominant,at least in a particular activity. A simple claim to competencein any sphere?be it painting, football, chess, or cooking?is oftensufficient to imbue a people with exaggerated importance.

    One's daily routine, which is subject to both individual and culturalinfluences, is filled with superficial comparison of one's ownhabits with foreign, often significantly different, habits. Even if wedo not know the sources of these differences, the simple fact thatthey exist can be enough to inspire fear or hatred. Human naturedoes not welcome change, even when we're dissatisfied with thingsas they are. Perhaps this devotion to habit and fear of meliorationencourage a conservatism that could lead to racism.

    There are unquestionable differences among peoples and nations.Language, skin color, tastes (especially in food), and greetingall differ among cultures and lead us to believe that othersare essentially not like us. We typically conclude that our ways arethe best, and too bad for the others. To the Greeks, all those whodid not speak Greek were barbarians. Of course, when a person isunsatisfied with life in his home country and migrates, he mightmore easily tolerate uncertainties and strange living conditions inanother region or continent. He might even accept the necessity oflearning new things. But in general, he prefers the cocoon in whichhe was born, terrified of discarding what is familiar.

    Many other factors nourish racist sentiments. One of the mostimportant is the desire to project one's unhappiness onto another.Everyone knows that self-alienation in modern society is often a veryserious cause of irritation and angst. These feelings can arise from thefear of unemployment, being forced to perform inhumane work, thereality and experience of poverty and injustice, and the feeling ofpowerlessness which often results from the jealous observation thatvast wealth is possible only for the very few. Everyone, even those whofeel victimized by their superiors, can assume authority over thoselower on the social ladder. The poor can always find somebody poorer.

    Because of all these factors, racism is widespread. It is lessapparent during times of peace and civil order. But hostilities aboutmass immigration from poor countries exacerbate it.

Is There a Scientific Basis for Racism?

Racism should be condemned because its effects are pernicious. It iscriticized by virtually every modern religion and ethical system.However, can we exclude the possibility that a superior race exists, orthat socially important, inherited differences between the races canbe found? There are certain obvious differences between humangroups for traits that depend to some extent on genes: skin color, eyeshape, hair type, facial form, and body shape. Will these and othertraits provide a scientific justification for racism? Do other differencesexist that might?

    We must first define the nature of the variation to be studied.Doing so helps us to understand what we mean by race, to decidewhich groups we should examine and what racial differences maytell us.

Biological and Cultural Varation

We must note that most people do not distinguish between biologicaland cultural heredity. It is often difficult to recognize whichis which. Sometimes the cause of racial difference is biological(in which case we call it genetic, meaning that it comes with yourDNA); sometimes it is behavioral, learned from someone else(these are cultural causes); and sometimes both factors are involved.Genetically determined traits are very stable over time, unlikesocially determined or learned behavior, which can change veryrapidly. As I said above, there are clear biological differencesbetween populations in the visual characteristics that we use to classifythe races. If these genetic differences were found to be genuinelyimportant and could support the sense of superiority that onepeople can have over another, then racism is justified?at leastformally. I find this genetic or biological definition of racism moresatisfactory than others. Some would extend the domain of racistjudgments to include any difference between groups, even themost superficial cultural characteristics. The only advantage of thisbroader definition is that it sidesteps the difficulty of determiningwhether certain traits have a genetic component or not. But it doesnot seem appropriate to speak of racism when one person resentsanother's loud voice, noisy eating habits, taste in dress, or difficultieswith correct pronunciation. This type of intolerance, which is rathercommon in certain countries or social classes, seems much easier tocorrect and control through education than is true racism.

Visible and Hidden Variation

The racial differences that impressed our ancestors and that continueto bother many people today include skin color, eye shape,hair type, body and facial form?in short, the traits that often allowus to determine a person's origin in a single glance. Ignoring admixture,it is fairly easy to recognize a European, an African, and anAsian, to mention those standard types with which we are mostfamiliar. Many of these characteristics?almost homogeneous on aparticular continent?give us the impression that "pure" races exist,and that the differences between them are pronounced. Thesetraits are at least partly genetically determined. Skin color and bodysize are less subject to genetic influence since they are also affectedby exposure to the sun and diet, but there is always a hereditarycomponent that can be quite important.

    These characteristics influence us a lot, because we recognizethem easily. What causes them? It is almost certain they evolved inthe most recent period of human evolution, when "modern" humans,or early humans practically undistinguishable from ourselves, firstappeared in Africa, grew in numbers, and began to expand to theother continents. Evidence and details will be discussed later. Whatinterests us here is that this diaspora of Africans to the rest of theworld exposed them to a great variety of environments: from hotand humid or hot and dry environments (to which they werealready accustomed) to temperate and cold ones, including thecoldest ones of the world, as in Siberia. We can go through some ofthe steps that this entailed.

    1. Exposure to a new environment inevitably causes an adaptationto it. In the 50,000-100,000 years since the African diaspora,there has been an opportunity for substantial adaptation, both culturaland biological. We can see traces of the latter in skin color andin size and shape of the nose, eyes, head, and body. One can say thateach ethnic group has been genetically engineered under the influenceof the environments where it settled. Black skin color protectsthose who live near the equator from burning under the sun's ultravioletradiation, which can also lead to deadly skin cancers. Thedairy-poor diet of European farmers, based almost entirely on cerealsthat lack ready-made vitamin D, might have left them vulnerableto rickets (our milk still has to be enriched with this vitamin). Butthey were able to survive at the higher latitudes to which theymigrated from the Middle East because the essential vitamin can beproduced, with the aid of sunlight, from precursor molecules foundin cereals. For this Europeans have developed the whiteness of theirskin, which the sun's ultraviolet radiation can penetrate to transformthese precursors into vitamin D. It is not without reason that Europeanshave, on average, whiter skin the further north they are born.

    The size and shape of the body are adapted to temperature andhumidity. In hot and humid climates, like tropical forests, it isadvantageous to be short since there is greater surface area for theevaporation of sweat compared to the body's volume. A smallerbody also uses less energy and produces less heat. Frizzy hair allowssweat to remain on the scalp longer and results in greater cooling.With these adaptations, the risk of overheating in tropical climatesis diminished. Populations living in tropical forests generally areshort, Pygmies being the extreme example. The face and body ofthe Mongols, on the other hand, result from adaptations to the bittercold of Siberia. The body, and particularly the head, tends to beround, increasing body volume. The evaporative surface area of theskin is thus reduced relative to body volume, and less heat is lost.The nose is small and less likely to freeze, and the nostrils are narrow,warming the air before it reaches the lungs. Eyes are protectedfrom the cold Siberian air by fatty folds of skin. These eyes are oftenconsidered beautiful, and Charles Darwin wondered if racial differencesmight not result from the particular tastes of individuals. Hecalled the idea that mates were chosen for their attractive quality"sexual selection." It is very likely that some characteristics undergosexual selection?eye color and shape, for example. But the shapeof Asian eyes is not appreciated only in Asia. If it is admired elsewhere,why is it not found in other parts of the world? Of course it isalso characteristic of the Bushmen of southern Africa, and otherAfricans have slanted eyes. It probably diffused by sexual selectionfrom northeastern Asia to Southeast Asia, where it is not at all cold.It is also possible that the trait may have originated more than oncein the course of human evolution. If it first appears that climaticfactors were most important in the creation of racial differences, weshould not neglect sexual selection as a possible side explanation.Unfortunately, the genetic bases for these adaptations are notknown; each of these traits is very complex. Considerable local variationin tastes further complicates the matter.

    2. There is little climatic variation in the area where a particularpopulation lives, but there are significant variations between the climatesof the Earth. Therefore, adaptive reactions to climate mustgenerate groups that are genetically homogeneous in an area that isclimatically homogeneous, and groups that are very different inareas with different climates.

    We could ask if sufficient time has passed since the settling ofthe continents to produce these biological adaptations. The selectionintensity has been very strong, so the answer is probably yes.We could note in this regard that the Ashkenazi Jews who havelived in central and eastern Europe for at least 2,000 years havemuch lighter skin than the Sephardi Jews who have lived on theMediterranean perimeter for at least the same length of time. Thiscould be an example of natural selection, but it might also resultfrom genetic exchange with neighboring populations. Some availablegenetic information favors the second interpretation, but bettergenetic data are desirable before we can exclude the influenceof natural selection.

    3. Adaptations to climate primarily affect surface characteristics.The interface between the interior and exterior plays thebiggest part in the exchange of heat from the interior to the exteriorand vice versa. A simple metaphor can help explain this statement:if you want to decrease the cost of heating your house in the winter,or cooling it in the summer, you must increase the house's insulationso that the thermal flow between the inside and outside isminimal. Thus, body surface has been largely modified to adapt differentpeople to different environments.

    4. We can see only the body's surface, as affected by climate,which distinguishes one relatively homogeneous population fromanother. We are therefore misled into thinking that races are "pure"(meaning homogeneous) and very different, one from the other. Itis difficult to find another reason to explain the enthusiasm of nineteenth-centuryphilosophers and political scientists like Gobineauand his followers for maintaining "racial purity." These men wereconvinced that the success of whites was due to their racialsupremacy. Because only visible traits could be studied then, it wasnot absurd to imagine that pure races existed. But today we knowthat they do not, and that they are practically impossible to create.To achieve even partial "purity" (that is, a genetic homogeneity thatis never achieved spontaneously in populations of higher animals)would require at least twenty generations of "inbreeding" (e.g., bybrother-sister or parent-children matings repeated many times).Such inbreeding would have severe consequences for the healthand fertility of the children, and we can be sure that such anextreme inbreeding process has never been attempted in our history,with a few minor and partial exceptions.

    In more recent times, the careful genetic study of hidden variation,unrelated to climate, has confirmed that homogeneous racesdo not exist. It is not only true that racial purity does not exist innature: it is entirely unachievable, and would not be desirable. It istrue, however, that "cloning," which is now a reality in animals notvery remote from us, can generate "pure" races. Identical twins areexamples of living human clones. But creating human races artificiallyby cloning would have potentially very dangerous consequences,both biologically and socially.

    We shall also see that the variation between races, defined bytheir continent of origin or other criteria, is statistically smalldespite the characteristics that influence our perception that racesare different and pure. That perception is truly superficial?beinglimited to the body surface, which is determined by climate. Mostlikely only a small bunch of genes are responsible, and little significanceis attached to them, especially since we are progressivelydeveloping a totally artificial climate.

Hidden Variation: Genetic Polymorphisms

The ABO blood group was the first example of an invisible and completelyhereditary trait. Discovered at the beginning of the century,it has been the subject of numerous studies, because the matchingof blood types is essential for successful blood transfusions. Thereare three major forms of the gene (also called "alleles"): A, B, and O,and they are strictly hereditary. An individual can have one of fourpossible blood types: O, A, B, and AB.

    Although it is not truly essential for the understanding of whatfollows, it is difficult to resist the opportunity of mentioning at thispoint a basic rule of inheritance: each of us receives one allele fromeach parent?one from the father and one from the mother. ThereforeAB blood type arises when an individual receives gene A fromone parent and gene B from the other. O blood type arises when anindividual receives O from both parents. A type, however, can be oftwo different genetic constitutions, AO and AA: the first receive Afrom one parent and O from the other, the second receive A fromboth parents. A similar situation applies to blood group B.

    The existence of genetic polymorphism (a situation in which agene exists in at least two different forms?or alleles) is demonstratedby the reaction of different blood types to specific reagents.To determine a blood type, two reagents are needed (anti-A andanti-B), which react with red blood cells (small oxygen-bearingblood cells invisible to the eye). The reaction is performed by addingtwo small drops of a patient's blood to a glass slide. A positive reactionoccurs if, after adding a reagent, the blood cells clump together.Because blood's color is due to the red blood cells, when they clumptogether, the remainder of the blood becomes clear. If the reactionis negative, the blood drop remains a consistent red colon Bloodgroup A individuals react positively only to the anti-A, while bloodgroup B reacts only with anti-B. Those with blood group O fail toreact with either serum, while AB individuals react with both.

    To simplify the statistics, we do not count the number of differentindividuals or genotypes, but only the number of alleles?twoper person. However, we have no way to distinguish between individualsof polymorphic blood group A, who could be either AA orAO. So, too, with B type blood. Luckily, simple mathematical techniquesallow us to estimate how many individuals are AA and howmany are AO (or BB and BO).

    During World War I, Ludwik and Hanka Hirschfeld, two Polishimmunologists, examined several different ethnic groups amongthe soldiers in the English and French colonial armies and theWorld War I prisoners, including Vietnamese, Senegalese, andIndians. They discovered that the proportions of individualsbelonging to the different blood groups were different in everypopulation. This phenomenon is now known to be universal. Weknow the number of polymorphisms is extremely high, and eachhuman population is different for most of the other polymorphisms,as well. This early work with ABO gave birth to anthropologicalgenetics.

Genetic Variation between Populations

The following table shows the frequency (in percent) of the ABOalleles by continent.

    We immediately notice wide variation among populations indifferent parts of the earth; each has a distinct gene frequency.The O gene always appears the majority type, varying from 61 to98 percent. The A gene varies from 1.7 to 27 percent, while theB gene varies from 0.3 to 19 percent. If we consider smaller samplesof Native Americans, the A and B genes might be completelyabsent.

    This table suggests two questions: Is this an exceptional situationor does something similar hold true for other genes as well?Can we explain why there is such great variation? For now, let'sexplore other genes and save the second question for later.

    After World War I, new blood group systems were developedusing the same methods that led to the discovery of the ABO system.The most complex group is the RH system, which was found amongEuropeans during World War II. Its study was quickly extended toseveral non-European populations. But aside from the ABO and RHsystems, very few blood group genes have clinical importance.Anthropological curiosity?the passion to know one's ancestors, relatives,and ultimate origins?has motivated many researchers to continuethe search for new genetic polymorphisms, which, performedby new genetic research techniques, is increasingly successful.

    Genetics, the study of heritable differences, offers us a windowthrough which to view that past. We know that, with few exceptions,many characteristics such as height and skin, hair, and eye color aregenetically determined, but we do not understand precisely how.Moreover, some of them are also influenced by non-genetic factors,for instance, nutrition, in the case of height, and exposure to the sun,in the case of skin tone. Our poor understanding of the hereditarymechanism of these familiar characteristics is due to their interactionwith non-genetic, environmental factors, and the general complexityof the mechanisms determining all traits that involve shape.By contrast, we understand clearly the inheritance of blood groups,and of chemical polymorphisms among enzymes and other proteins,because the account of traits determined by relatively simple substanceslike proteins is chemically simpler and easier to understandand measure. But these traits are not directly visible, and rather sensitivelaboratory methods are required to detect them.

    Very early on, the American scientist William Boyd showed thatby using the first genetic systems discovered?ABO, RH, andMN?one could already differentiate populations from the fivecontinents. Arthur Mourant, a British hematologist, produced thefirst comprehensive summary of data on human polymorphisms in1954. The second edition of Mourant's book, appearing in 1976,contained more than one thousand pages, more than doubling theamount of data previously available.

    Two major techniques are used to study polymorphisms, orgenetic "markers" as they are called because they act as tags ongenetic material, on proteins. One, employed for almost all bloodgroup typings, uses biological reagents, often made by humansreacting to foreign substances from bacteria, or from other sources.These reagents are special proteins called immunoglobulins orantibodies. They are made in the course of building immunity, thatis, resistance to some external agent, and usually react specificallywith substances called antigens, usually other proteins. Theother analytical method of genetic analysis, developed in 1948, is adirect study of physical properties of specific protein molecules,usually by measuring their mobility in an electric field. It is calledelectrophoresis.

    Both methods revealed directly or indirectly the variation instructure of specific proteins from individual to individual. Thebehavior of these variants could be tested in families to confirm thegenetic nature of such variation. But the number of polymorphicproteins detected in this way was small and at the beginning of the1980s only about 250 were known. All proteins are produced byDNA, and therefore behind protein variation there must be a parallelvariation of DNA, the chemical substance responsible for biologicalinheritance. The analytical methods necessary to chemicallystudy DNA were developed later.

    In the early eighties the analysis of variation in DNA had itsstart. DNA is a very long filament made of a chain combining fourdifferent nucleotides, A, C, G, and T. Changes in the sequence ofnucleotides of a specific DNA happen rarely, and more or less randomly,when one nucleotide is replaced by another during replication.Thus, if a DNA segment is GCAATGGCCC, it may happenthat a copy of it passed by a parent to a child is changed in the fifthnucleotide, T being replaced by C. The DNA generating the child'sprotein will thus be GCAACGGCCC. This is the smallest changethat can happen to DNA, and is called a mutation; as DNA is inherited,descendants of the child will receive the mutated DNA. Achange in DNA may cause a change in a protein, and this may causea change visible to us.

    Restriction enzymes provided a simple way to detect differencesin the DNA of two individuals. Restriction enzymes are producedby bacteria and break DNA into certain sequences of 4, 6, or8 nucleotides, for instance GCCG.

    A method of multiplying DNA in a test tube with the enzymeDNA polymerase, which nature uses to duplicate DNA when cellsdivide, was discovered and developed in the second half of the eighties,and is called PCR, or polymerase chain reaction. This new techniquehas improved the power of genetic analysis in the nineties. Wenow know that there must exist millions of polymorphisms in DNA,and we can study them all, but the techniques for doing this at a satisfactorypace are only now beginning to be available.

    The future of the analysis of genetic variation is clearly in thestudy of DNA, but results accumulated with the old techniquesbased on proteins have not lost their value. There are some specificproblems, which can be resolved only by DNA techniques. On theother hand, the very rich information generated by protein data onhuman populations includes almost 100,000 frequencies of polymorphisms.They were studied for over 100 genes in thousands ofdifferent populations all over the earth, and many of the conclusionsthus made possible and discussed in this book have arisen from studiesof proteins. Results with DNA have complemented but nevercontradicted the protein data. We start having knowledge on thousandsof DNA polymorphisms, but they are almost all limited to veryfew populations. We will summarize the most important ones.

Studying Many Genes Allows Use of the "Law of Large Numbers"

Is it possible to reconstruct human evolution by studying the typesof living populations only? We can simplify the process of doing soby concentrating most of our studies to indigenous people, when itis possible to recognize them and differentiate them from recentimmigrants to a region. But we learn much about human originsand evolution from a single gene like ABO.

    We will introduce here the word "gene." Everybody has heard it,but few know its precise meaning. The old definition, "unit of inheritance,"is still difficult to understand in fact, it was used when wedid not know what a gene was in chemical terms. Today we can givea much more concrete definition: a gene is a segment of DNA thathas a specified, recognizable biological function (in practice, mostfrequently that of generating a particular protein). It is, therefore,part of a chromosome, a rod found in the nucleus of a cell that containsan extremely long DNA thread, coiled and organized in a complicatedway. A cell usually has many chromosomes, and theirdistribution to daughter cells is made in such a way that a daughtercell receives a complete copy of the chromosomes of the mothercell. When studying evolution, however, we may, and often must,ignore what a gene is doing, because we don't know. But a generemains useful for evolutionary studies (and others) if it is present inmore than one form, and the more forms of a gene (allele) that exist,the better the gene suits our purposes. With only three alleles, ABOcan hardly be very informative. In Africa, the place of origin, onefinds all alleles. But this is also true of Asia and Europe. In Asia,however, the B allele is more frequent than in the other continents;group A is somewhat more common in Europe; and Native Americansare almost entirely blood group O. What conclusions can wedraw? That A and B genes were probably lost in the majority ofNative Americans, but why? Many have speculated about the reason,but it is impossible to provide an entirely satisfactory answer.

    The first hypothesis connecting the historical origin of a peopleand a gene that was subsequently confirmed by independent evidencewas made on the basis of the RH gene in the early forties.The simplest genetic analysis recognizes two forms: RH + and RH-.Globally, RH+ is predominant, but RH- reaches appreciable frequenciesin Europe with the Basques having the highest frequency.This suggests that the RH- form arose by mutation from the RH+allele in western Europe and then spread, for unspecified reasons,toward Asia and Africa, never greatly diminishing the frequency ofthe RH+ gene. The highest frequencies of the negative type aregenerally found in the west and northeast of Europe. Frequenciessteadily decline toward the Balkans, as if Europe was once entirelyRH-(or at least predominantly so) before a group of RH+ peopleentered via the Balkans and diffused to the west and north, mixingwith indigenous Europeans. This hypothesis would have remaineduncertain if it had not been substantiated by the simultaneous studyof many other genes. Archeology also lent support to the argument,as we shall see later.

    Reconstructing the history of evolution has proved a dauntingtask. The accumulation of data on many genes in thousands of peoplefrom different populations has produced a dizzying amount ofinformation that describes the frequency of the different forms ofmore than 100 genes?a body of knowledge that is very useful fortesting evolutionary hypotheses. Experience has shown that we cannever rely on a single gene for reconstructing human evolution. Itmight appear that a single system of genes like HLA, which todayhas hundreds of alleles, would be sufficient. The HLA genes play animportant role in fighting infections and recently have becomeimportant in matching donors and recipients for tissue and organtransplants. They possess a great diversity of forms, as is necessaryfor a potential defense against the spread of tumors among unrelatedindividuals, but they are also subject to extreme natural selectionrelated to their role in fighting infection. If the conclusions wereach about evolution through observations made using HLA aredifferent from those obtained using other genes, we need to explainthe reasons, because they may lead to different historical interpretations.It is very useful, and I think essential, to examine all existinginformation. The broadest synthesis has the greatest chance ofanswering the questions we ask, and the least chance of being contradictedby later findings.

    Therefore, it is also worth gathering information from any disciplinethat can provide even a partial answer to our problems.Within genetics itself, we want to collect as much information aboutas many genes as possible, which would allow us to use the "law oflarge numbers" in the calculation of probabilities: random events areimportant in evolution, but despite their capriciousness, their behaviorcan be accounted for through a large number of observations.Jacques Bernoulli, in his Ars conjectandi of 1713, wrote, "Even thestupidest of men, by some instinct of nature, is convinced on his ownthat with more observations his risk of failure is diminished."

    Many studies have been invalidated because of an inadequatenumber of observations. When we study polymorphisms directly onDNA, there is no dearth of evidence: we can study millions. Wemay not need to study them all, because at a certain point additionaldata fail to provide new results or lead to different conclusions.Nevertheless, simply studying a large sample is not alwaysenough. If we observe heterogeneity in our data, so that it can bedivided into several categories, each implying a different history, wemust further search for the source of these discrepancies. We haveseen an important example in the comparison of genes transmittedby the paternal and the maternal line, as we will discuss in anotherchapter.

Continues...

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