In our blood there is protein which is RH+ what if we don't have protein will we be stronger with protein?

Answer 1

People are just fine either with or with the Rh factor. This factor doesn't affect a person's health or strength.

However, if an Rh- woman has an Rh+ baby, she could make defenses against any future Rh+ babies. Hospitals give Rh- women a shot of Rhogam (unless it has another name now) to prevent these complications.

Answer 2

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

I recently reread his play Copernicus, which I still find relevant and insightful. The characters include the Sun, the First and Last Hours of the Day, and Copernicus. In the opening scene, the Sun confides to the First Hour that he is tired of revolving around the Earth each day, and demands that the Earth shoulder some of the burden. The First Hour, alarmed by this prospect, points out that the Sun's retirement would create havoc. But the Sun is adamant and insists on informing Earth's philosophers of the impending change since he believes they can convince humans of anything—good or bad. By the 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 summoned to hear the Sun's proposal: the Earth must renounce her position at the center of the Universe and instead revolve around the Sun. Copernicus notes that even philosophers would have difficulty convincing the Earth of that. Moreover, the Earth and her inhabitants have grown accustomed to their position at the center of the Universe and have developed the "pride of an emperor." A change of such magnitude would have not only physical but also social and philosophical consequences. The most basic assumptions about human life would be overturned. But the Sun is insistent that life will go on, that all the barons, dukes, and emperors will continue to believe in their importance, and that their power won't be weakened in the least. Copernicus offers further objections: a galactic revolution could begin—the other planets may assert that they want the same rights to centrality as the Earth had. Even the stars would protest. In the end, the Sun might lose all importance and be forced to find another orbit. But the Sun desires only rest and counters Copernicus's final fear—that he will be burned as a heretic—by telling him he can avoid such a fate by dedicating his book to the Pope.

In writing about Copernicus, Leopardi had the benefit of living several centuries after him. He knew what had happened to Copernicus, Giordano Bruno, and Galileo. But we do not have Leopardi's advantage when considering the scientific issues of our day. Any current theories may be modified or even destroyed at any moment. In fact, science progresses because every hypothesis can be confirmed or rejected by others. The great number of conditionals we use in our scientific prose underscore this truth. While correcting the translation of one of my books, I was terrified to see that all my conditionals had been changed to indicatives—my safeguards had been eliminated. When we write papers for scientific journals, we know 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 alone is immune from doubt, although few believers seem troubled by the fact that each religion offers different answers. Mathematics may be the only exception in the sciences that leaves no room for skepticism. But, if mathematical results are exact as no empirical law could ever be, philosophers have discovered they are not absolutely novel—instead, they are tautological.




Copernicus also reminded me of our attitudes about race and racism. Each population believes that it is the best in the world. With few exceptions, people love the microcosm into which they are born and don't want to leave it. For Whites, the greatest civilization is European; the best race is White (French in France and English in England). But what do the Chinese think? And the Japanese? Wouldn't most of today's recent immigrants return to their 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 families come and go—there is an increasingly rapid turnover of power—but power structures change very little. The Roman Empire lasted longer than many others in Europe, but it spanned only five centuries. It was similar in size to the Inca Empire, which lasted a little more than a century. Before the Roman Empire, several maritime powers—the Greeks, Phoenicians, and Carthaginians—colonized the Mediterranean coast. At the same time, the European interior saw Celtic princes establish control over most of Europe. During the second half of the first millennium B.C., the Celtic and maritime fiefdoms were each united by commercial, linguistic, and cultural ties, but were politically fragmented.

Ultimately, they would all fall to the Romans. The Romans built the first politically united culture in Europe, but it eventually fell to "barbarian" invaders from the East. The barbarians flourished, and only the eastern part of the Roman Empire—the Byzantine Empire—was to survive into the Middle Ages. In the west, Charlemagne founded the Holy Roman Empire in A.D. 800, the culmination of Frankish political development. France, Germany, and parts of Italy and Spain were briefly reunited. After A.D. 1000, Frankish power passed to Germany and, in part, to the Pope, although the Papacy and the Empire were often in conflict. The Holy Roman Empire ceased to have any political importance by the fourteenth century, although Austrian emperors continued to take the title of Holy Roman Emperor until 1806. Several European states were formed or consolidated between 1000 and 1500. Although wars among them were frequent, none was able to conquer much of Europe before Napoleon. With the development of seaworthy ships, the armies and navies of Europeans attempted to extend their hegemony to the rest of the world, competing for national riches on other continents. The Portuguese, Spanish, English, Dutch, French, and Russians established overseas empires which would 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 rule lasted for fewer than ten years.

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

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

Perhaps Claude Lévi-Strauss most succinctly defined racism as the belief that one race (usually, though not always, one's own) is biologically superior—that superior genes, chromosomes, DNA put it at an advantage over all others. This is America's situation now. It is no coincidence that you must first dial the number one when calling the United States from abroad.

At any particular moment, a single people may be dominant despite the many countries that have been before, or will be soon. Of course, it is not necessary to be superior to be convinced that one is. Even a limited success can demonstrate power to others. Many believe 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 competence in any sphere—be it painting, football, chess, or cooking—is often sufficient to imbue a people with exaggerated importance.

One's daily routine, which is subject to both individual and cultural influences, is filled with superficial comparison of one's own habits with foreign, often significantly different, habits. Even if we do not know the sources of these differences, the simple fact that they exist can be enough to inspire fear or hatred. Human nature does not welcome change, even when we're dissatisfied with things as they are. Perhaps this devotion to habit and fear of melioration encourage a conservatism that could lead to racism.

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

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

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




Is There a Scientific Basis for Racism?




Racism should be condemned because its effects are pernicious. It is criticized by virtually every modern religion and ethical system. However, can we exclude the possibility that a superior race exists, or that socially important, inherited differences between the races can be found? There are certain obvious differences between human groups for traits that depend to some extent on genes: skin color, eye shape, hair type, facial form, and body shape. Will these and other traits provide a scientific justification for racism? Do other differences exist 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 decide which groups we should examine and what racial differences may tell us.




Biological and Cultural Varation




We must note that most people do not distinguish between biological and cultural heredity. It is often difficult to recognize which is which. Sometimes the cause of racial difference is biological (in which case we call it genetic, meaning that it comes with your DNA); 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, unlike socially determined or learned behavior, which can change very rapidly. As I said above, there are clear biological differences between populations in the visual characteristics that we use to classify the races. If these genetic differences were found to be genuinely important and could support the sense of superiority that one people can have over another, then racism is justified—at least formally. I find this genetic or biological definition of racism more satisfactory than others. Some would extend the domain of racist judgments to include any difference between groups, even the most superficial cultural characteristics. The only advantage of this broader definition is that it sidesteps the difficulty of determining whether certain traits have a genetic component or not. But it does not seem appropriate to speak of racism when one person resents another's loud voice, noisy eating habits, taste in dress, or difficulties with correct pronunciation. This type of intolerance, which is rather common in certain countries or social classes, seems much easier to correct and control through education than is true racism.




Visible and Hidden Variation




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

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

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

The size and shape of the body are adapted to temperature and humidity. In hot and humid climates, like tropical forests, it is advantageous to be short since there is greater surface area for the evaporation of sweat compared to the body's volume. A smaller body also uses less energy and produces less heat. Frizzy hair allows sweat to remain on the scalp longer and results in greater cooling. With these adaptations, the risk of overheating in tropical climates is diminished. Populations living in tropical forests generally are short, Pygmies being the extreme example. The face and body of the Mongols, on the other hand, result from adaptations to the bitter cold of Siberia. The body, and particularly the head, tends to be round, increasing body volume. The evaporative surface area of the skin 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 protected from the cold Siberian air by fatty folds of skin. These eyes are often considered beautiful, and Charles Darwin wondered if racial differences might not result from the particular tastes of individuals. He called the idea that mates were chosen for their attractive quality "sexual selection." It is very likely that some characteristics undergo sexual selection—eye color and shape, for example. But the shape of 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 is also characteristic of the Bushmen of southern Africa, and other Africans have slanted eyes. It probably diffused by sexual selection from northeastern Asia to Southeast Asia, where it is not at all cold. It is also possible that the trait may have originated more than once in the course of human evolution. If it first appears that climatic factors were most important in the creation of racial differences, we should not neglect sexual selection as a possible side explanation. Unfortunately, the genetic bases for these adaptations are not known; each of these traits is very complex. Considerable local variation in tastes further complicates the matter.

2. There is little climatic variation in the area where a particular population lives, but there are significant variations between the climates of the Earth. Therefore, adaptive reactions to climate must generate groups that are genetically homogeneous in an area that is climatically homogeneous, and groups that are very different in areas with different climates.

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

3. Adaptations to climate primarily affect surface characteristics. The interface between the interior and exterior plays the biggest part in the exchange of heat from the interior to the exterior and 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 insulation so that the thermal flow between the inside and outside is minimal. Thus, body surface has been largely modified to adapt different people to different environments.

4. We can see only the body's surface, as affected by climate, which distinguishes one relatively homogeneous population from another. We are therefore misled into thinking that races are "pure" (meaning homogeneous) and very different, one from the other. It is difficult to find another reason to explain the enthusiasm of nineteenth-century philosophers and political scientists like Gobineau and his followers for maintaining "racial purity." These men were convinced that the success of whites was due to their racial supremacy. Because only visible traits could be studied then, it was not absurd to imagine that pure races existed. But today we know that they do not, and that they are practically impossible to create. To achieve even partial "purity" (that is, a genetic homogeneity that is never achieved spontaneously in populations of higher animals) would require at least twenty generations of "inbreeding" (e.g., by brother-sister or parent-children matings repeated many times). Such inbreeding would have severe consequences for the health and fertility of the children, and we can be sure that such an extreme 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 races do not exist. It is not only true that racial purity does not exist in nature: it is entirely unachievable, and would not be desirable. It is true, however, that "cloning," which is now a reality in animals not very remote from us, can generate "pure" races. Identical twins are examples of living human clones. But creating human races artificially by cloning would have potentially very dangerous consequences, both biologically and socially.

We shall also see that the variation between races, defined by their continent of origin or other criteria, is statistically small despite the characteristics that influence our perception that races are different and pure. That perception is truly superficial—being limited to the body surface, which is determined by climate. Most likely only a small bunch of genes are responsible, and little significance is attached to them, especially since we are progressively developing a totally artificial climate.




Hidden Variation: Genetic Polymorphisms




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

Although it is not truly essential for the understanding of what follows, it is difficult to resist the opportunity of mentioning at this point a basic rule of inheritance: each of us receives one allele from each parent—one from the father and one from the mother. Therefore AB blood type arises when an individual receives gene A from one parent and gene B from the other. O blood type arises when an individual receives O from both parents. A type, however, can be of two different genetic constitutions, AO and AA: the first receive A from one parent and O from the other, the second receive A from both parents. A similar situation applies to blood group B.

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

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

During World War I, Ludwik and Hanka Hirschfeld, two Polish immunologists, examined several different ethnic groups among the soldiers in the English and French colonial armies and the World War I prisoners, including Vietnamese, Senegalese, and Indians. They discovered that the proportions of individuals belonging to the different blood groups were different in every population. This phenomenon is now known to be universal. We know the number of polymorphisms is extremely high, and each human population is different for most of the other polymorphisms, as well. This early work with ABO gave birth to anthropological genetics.




Genetic Variation between Populations




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




Region A B O

Europe 27 8 65
English 25 8 67
Italian 20 7 73
Basques 23 2 75
East Asia 20 19 61
Africa 18 13 69
American Natives 1.7 0.3 98
Australian Natives 22 2 76





We immediately notice wide variation among populations in different parts of the earth; each has a distinct gene frequency. The O gene always appears the majority type, varying from 61 to 98 percent. The A gene varies from 1.7 to 27 percent, while the B gene varies from 0.3 to 19 percent. If we consider smaller samples of Native Americans, the A and B genes might be completely absent.

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

After World War I, new blood group systems were developed using the same methods that led to the discovery of the ABO system. The most complex group is the RH system, which was found among Europeans during World War II. Its study was quickly extended to several non-European populations. But aside from the ABO and RH systems, 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 continue the search for new genetic polymorphisms, which, performed by new genetic research techniques, is increasingly successful.

Genetics, the study of heritable differences, offers us a window through which to view that past. We know that, with few exceptions, many characteristics such as height and skin, hair, and eye color are genetically 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 hereditary mechanism of these familiar characteristics is due to their interaction with non-genetic, environmental factors, and the general complexity of 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 substances like proteins is chemically simpler and easier to understand and measure. But these traits are not directly visible, and rather sensitive laboratory methods are required to detect them.

Very early on, the American scientist William Boyd showed that by using the first genetic systems discovered—ABO, RH, and MN—one could already differentiate populations from the five continents. Arthur Mourant, a British hematologist, produced the first comprehensive summary of data on human polymorphisms in 1954. The second edition of Mourant's book, appearing in 1976, contained more than one thousand pages, more than doubling the amount of data previously available.

Two major techniques are used to study polymorphisms, or genetic "markers" as they are called because they act as tags on genetic material, on proteins. One, employed for almost all blood group typings, uses biological reagents, often made by humans reacting to foreign substances from bacteria, or from other sources. These reagents are special proteins called immunoglobulins or antibodies. They are made in the course of building immunity, that is, resistance to some external agent, and usually react specifically with substances called antigens, usually other proteins. The other analytical method of genetic analysis, developed in 1948, is a direct study of physical properties of specific protein molecules, usually by measuring their mobility in an electric field. It is called electrophoresis.

Both methods revealed directly or indirectly the variation in structure of specific proteins from individual to individual. The behavior of these variants could be tested in families to confirm the genetic nature of such variation. But the number of polymorphic proteins detected in this way was small and at the beginning of the 1980s only about 250 were known. All proteins are produced by DNA, and therefore behind protein variation there must be a parallel variation of DNA, the chemical substance responsible for biological inheritance. The analytical methods necessary to chemically study DNA were developed later.

In the early eighties the analysis of variation in DNA had its start. DNA is a very long filament made of a chain combining four different nucleotides, A, C, G, and T. Changes in the sequence of nucleotides 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 happen that a copy of it passed by a parent to a child is changed in the fifth nucleotide, T being replaced by C. The DNA generating the child's protein will thus be GCAACGGCCC. This is the smallest change that can happen to DNA, and is called a mutation; as DNA is inherited, descendants of the child will receive the mutated DNA. A change in DNA may cause a change in a protein, and this may cause a change visible to us.

Restriction enzymes provided a simple way to detect differences in the DNA of two individuals. Restriction enzymes are produced by bacteria and break DNA into certain sequences of 4, 6, or 8 nucleotides, for instance GCCG.

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

The future of the analysis of genetic variation is clearly in the study of DNA, but results accumulated with the old techniques based on proteins have not lost their value. There are some specific problems, which can be resolved only by DNA techniques. On the other hand, the very rich information generated by protein data on human populations includes almost 100,000 frequencies of polymorphisms. They were studied for over 100 genes in thousands of different populations all over the earth, and many of the conclusions thus made possible and discussed in this book have arisen from studies of proteins. Results with DNA have complemented but never contradicted the protein data. We start having knowledge on thousands of DNA polymorphisms, but they are almost all limited to very few 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 types of living populations only? We can simplify the process of doing so by concentrating most of our studies to indigenous people, when it is possible to recognize them and differentiate them from recent immigrants to a region. But we learn much about human origins and 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 we did not know what a gene was in chemical terms. Today we can give a much more concrete definition: a gene is a segment of DNA that has a specified, recognizable biological function (in practice, most frequently that of generating a particular protein). It is, therefore, part of a chromosome, a rod found in the nucleus of a cell that contains an extremely long DNA thread, coiled and organized in a complicated way. A cell usually has many chromosomes, and their distribution to daughter cells is made in such a way that a daughter cell receives a complete copy of the chromosomes of the mother cell. When studying evolution, however, we may, and often must, ignore what a gene is doing, because we don't know. But a gene remains useful for evolutionary studies (and others) if it is present in more than one form, and the more forms of a gene (allele) that exist, the better the gene suits our purposes. With only three alleles, ABO can hardly be very informative. In Africa, the place of origin, one finds 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 Americans are almost entirely blood group O. What conclusions can we draw? That A and B genes were probably lost in the majority of Native 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 people and a gene that was subsequently confirmed by independent evidence was 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 frequencies in 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 of the RH+ gene. The highest frequencies of the negative type are generally found in the west and northeast of Europe. Frequencies steadily decline toward the Balkans, as if Europe was once entirely RH-(or at least predominantly so) before a group of RH+ people entered via the Balkans and diffused to the west and north, mixing with indigenous Europeans. This hypothesis would have remained uncertain if it had not been substantiated by the simultaneous study of many other genes. Archeology also lent support to the argument, as we shall see later.

Reconstructing the history of evolution has proved a daunting task. The accumulation of data on many genes in thousands of people from different populations has produced a dizzying amount of information that describes the frequency of the different forms of more than 100 genes—a body of knowledge that is very useful for testing evolutionary hypotheses. Experience has shown that we can never rely on a single gene for reconstructing human evolution. It might appear that a single system of genes like HLA, which today has hundreds of alleles, would be sufficient. The HLA genes play an important role in fighting infections and recently have become important in matching donors and recipients for tissue and organ transplants. They possess a great diversity of forms, as is necessary for a potential defense against the spread of tumors among unrelated individuals, but they are also subject to extreme natural selection related to their role in fighting infection. If the conclusions we reach about evolution through observations made using HLA are different from those obtained using other genes, we need to explain the reasons, because they may lead to different historical interpretations. It is very useful, and I think essential, to examine all existing information. The broadest synthesis has the greatest chance of answering the questions we ask, and the least chance of being contradicted by later findings.

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

Many studies have been invalidated because of an inadequate number of observations. When we study polymorphisms directly on DNA, there is no dearth of evidence: we can study millions. We may not need to study them all, because at a certain point additional data fail to provide new results or lead to different conclusions. Nevertheless, simply studying a large sample is not always enough. If we observe heterogeneity in our data, so that it can be divided into several categories, each implying a different history, we must further search for the source of these discrepancies. We have seen an important example in the comparison of genes transmitted by the paternal and the maternal line, as we will discuss in another chapter.