8 Chapter 8: Human Variation
My son is colorblind and has trouble distinguishing red and green and a few other colors. For a long time, he thought pumpkins were yellow and that we had a green couch. Now we refer to that couch as the “green couch” using finger quotes. His colorblindness is a result of a genetic mutation. In other cases, genetic mutations are more dramatic. On the island of Pingelap, about one in ten people are completely colorblind. That is, they see only in black and white. In the world population, the incidence of total colorblindness or achromatopsia is 1 in 40,000. How did this happen? It is said that a catastrophic typhoon hit the island of Pingelap in 1780 and the king, who had achromatopsia, was one of only 20 people that survived. Given the limited number of people, and perhaps the king’s personal charisma, the mutation for the condition spread over time. Unfortunately, this form of colorblindness also makes people very sensitive to the sun, and they can’t see very well at all during the daytime. One solution has been to fish at night, at which the Pingelap people excel. The achromatopsia mutation is an example of the Founder Effect, when a small number of people, in this case probably just one, influences the future prevalence of traits in the general population of a group. This chapter explores human variation, how we are the same and how we are different, and how we got to look the way we do.
The Code of Life
In 2003, The Human Genome Project mapped out the entire human genome, the entire set of genetic instructions for our species. All humans are, genetically speaking, very much alike, sharing 99.9 percent of our DNA in common. However, people aren’t identical and genes differ from one person to another. Phenotype refers to the expression of genes, such as height or hair color. Some phenotypic variation is not outwardly obvious, like blood type. When we talk about the genes themselves we use the term genotype. So how and why do humans vary?
DNA (deoxyribonucleic acid) is composed of nucleotides, which are molecules made up of sugars, phosphates, and nucleotide bases. There are only four bases: adenine, thymine, cytosine, guanine, and thymine—A, T, C, and G for short. Just as zeros and ones make up current computer systems, these four letters form the basis of all life on earth, from nematodes to narwhals. The bases are paired with one another—A with T and G with C—to form the steps of the DNA spiral ladder or double helix. The human genome, the complete set of genetic material, contains about 3 billion base pairs. If you took all the DNA in all your cells and strung it out end to end, you could make it out of the solar system! (Bryson 2019) But before we start celebrating our vast genome, it is now known that the axolotl, a kind of salamander native to Mexico, has 32 billion base pairs (Bakalar 2018). That’s 10 times the size of the human genome. This huge genome is likely related to the fact that axolotls can regrow limbs. So much for human exceptionalism in the base pair department.
Some sequences of nucleotide bases in the genome code for proteins. We call these genes. Perhaps humans have the most genes and that explains our dominance. It wasn’t so long ago that we did not know the total number of genes in the human genome. In the History of Everyone Who Ever Lived, geneticist Adam Rutherford describes how the world’s pre-eminent geneticists placed bets on the number of genes in the human genome, anticipating the results of the Human Genome Project. Some experts guessed around 100,000 genes. Today we know rice has 50,000 genes, bananas have 36,000, and the “water flea” 31,000. Humans, as revealed by the Human Genome Project, crossed the finish line at a disappointing 20,000 genes.
Mistakes Are Made
Occasionally when DNA replicates, a copying error or mutation occurs. These mutations occur randomly. With every child born, there are approximately 50 new mutations. Changes in a single base from one letter to another are called SNPs (“snips”) short for single nucleotide polymorphisms. SNPs are the most common form of genetic difference between people. Sometimes a change in one letter has no effect, other times, a SNP can affect a physical trait like eye color. And in rare cases, a SNP can lead to a debilitating disease like cystic fibrosis, sickle-cell anemia, or Huntington’s disease. SNPs account for much of human variation. Two people chosen at random are likely to differ in 1 in every 1,000 nucleotide bases or 0.1 percent. With the advent of companies that identify certain SNPs from a sample of spit, we are learning more about how SNPs are distributed around the world and what their effect is if any. There’s even a website called “SNPedia” that provides information about different SNPs. Other types of changes in bases can happen as well, including inversion, insertion, deletion, or duplication of bases which can result in human variation.
People inherit genes from both their mother and their father. The genes you inherit from each parent may be slightly different. These variants of genes, called alleles, are sometimes either dominant or recessive. A dominant allele will mask the expression of the recessive allele. Sometimes, you need two copies of the recessive allele for the disease to be expressed. Inbreeding within a population can lead to problems because a person is more likely to inherit two copies of a faulty allele. Carlos II (1661-1700), King of Spain, is a case in point. To protect the Spanish Hapsburg dynasty, marriages between cousins and between uncles and nieces were common in the royal line. As a result, Carlos’ family tree collapsed in on itself. Where Carlos should have been 64 ancestors, he had only 32 (Rutherford 2016). The result was that Carlos was physically and mentally infirm along with being infertile.
“Charles the II in His Twenties” by Luca Giordano is licensed under public domain
A famous SNP that caused disease originated with Queen Victoria of Great Britain. She was a carrier of hemophilia, a blood clotting disease. The SNP is thought to have arisen through spontaneous mutation, and she passed it on to some of her daughters and sons. Her children and grandchildren married nobility from around Europe and Russia, spreading the SNP to several royal families, earning hemophilia the name “royal’s disease”.
Populations Change over Time
Why do populations look different from others or have higher frequencies of certain SNPs than others? There are two important ways in which SNPs get distributed that we will discuss: founder effect and natural Selection. The founder effect happens when a small group of people establishes a population, bringing with them a limited about of genetic variation. The founding group is then isolated from others. Sometimes the founders bring with them chance mutations, so subsequent generations are more likely to have those mutations as well. For example, a form of dwarfism Ellis-van Creveld accompanied by polydactyly, having extra fingers, occurs in Amish populations in Pennsylvania due to the Founder Effect. The mutation can be traced back to a single couple (the “founders”). People practiced endogamy (marriage within the group) and the recessive gene for polydactyly was, therefore, more likely to occur than if they practiced exogamy (marriage outside the group). Likewise, on the remote island of Tristan da Cunha in the far south Atlantic, there are just 300 residents, but more than half of them suffer from asthma (Zamel et al. 1996). Why? Because of the 15 original settlers, two were asthma sufferers. On the Micronesian atoll of Pingelap, about one in ten people are totally colorblind, seeing only black and white. It is thought that a typhoon wiped out most of the population in 1775. The king, who was thought to have carried the defective gene, survived and passed it on to his many descendants. Interestingly though, those affected have excellent night vision.
Iceland’s founders are well documented through Íslendingabók, The Book of Icelanders. Many people are related, but may not know it. Because of the problem of potentially inheriting two copies of a deleterious (bad) gene or accidentally dating a cousin, some enterprising Icelanders developed the Islendiga-App, which warns you about dating potential relatives. If you bump phones and an alarm goes off, you may want to look elsewhere.
Northern New Mexico has also been shaped by founder effect. Many people in northern New Mexico have inherited a mutation that causes cerebral cavernous malformation (CCM). The disease causes blood vessels to form clusters in the brain and spinal cord producing headaches, seizures, and potentially strokes. The disease is caused by a mutation in the CCM1 gene, and unfortunately, the gene is dominant, so a person who has the mutation has a 50 percent chance of passing it on to their children. Some people with the gene have no symptoms, and there can be a wide range of severity. The disease derives from Cristóbal Baca, an early Spanish colonist of New Mexico in 1600. Researchers at the University of New Mexico Hospital and the Baca Family Historical Project are starting an effort to better diagnose people. (See this site if you have CCM and want to participate in a study to try to determine why the disease differs in severity).
Natural Selection
In natural selection, a trait has some advantage in a particular environment that causes individuals with that trait to survive and reproduce at a higher rate than individuals without the trait. Unlike founder effect, traits confer some advantage to the organism. A clear example of natural selection comes from the New Mexico rock pocket mouse. Mice that live in sandy desert areas of New Mexico are a sandy brown color, blending in with their environment from predators. But New Mexico also has several areas of lava flows like The Valley of Fire. In this region, mice tend to be grayer, blending in with the lava flow. More sandy coloration is a liability on the darker lava, and those mice are selected out of the population by being eaten by predators leaving the darker mice to survive and reproduce at a greater rate. Genetic studies show mutations in the MC1R gene leading to dark coloration. On different lava flows different mutations have been selected for resulting in dark coloration. Even if the dark mice have just a 1 percent advantage, 95% percent of mice will be dark in 1,000 years (HHMI). Importantly, the mutations occur at random, but natural selection acts upon those random mutations.
The same process, natural selection, that has shaped the rock pocket mouse has shaped the human phenotype, from lactose tolerance (a.k.a. Lactase persistence) to disease resistance to skin color. Human babies can digest lactose until about the age of 4 to 6, then the ability shuts down and people become lactose intolerant. In this case, the gene does not code for a protein but switches on and off the gene that produces lactase. In some populations, SNPs arose such that the ability to digest lactose never switches off and adults can drink milk freely. Not too surprisingly, populations that can drink milk are those where herding animals are important, or were important in the past, to their ancestral populations. This is a good example of how a cultural trait, herding, led to the selection of a biological trait, lactose tolerance. In fact, humans are the only mammal that can do this. Shaping our biology as a result of culture is called gene-culture co-evolution. The ability to digest milk, even if it conferred a small advantage, would have led to most people being lactose tolerant, similar to the pocket mouse example.
As with the pocket mouse example, different mutations led to lactose tolerance in different populations. Different SNPs account for lactose tolerance in Europe, Africa, and the Middle East. The same SNP accounts for lactose tolerance in Europe and India, indicating a common origin. In northern Europeans, lactose tolerance is a result of just one SNP, a mutation in a single base pair. The Masai cattle herders of Tanzania and other sub-Saharan Africans, however, have a different mutation that also results in lactose tolerance. Like the pocket mice, these mutations popped up randomly but were acted on through natural selection because they were advantageous in cultures with domesticated animals that could be milked.
Another example of natural selection in humans is the sickle cell trait. A disease called sickle cell anemia is caused by a variant of a gene that produces hemoglobin. The variant is caused by a single SNP, a switch from A (adenine) to T (thymine). Sickle cell anemia is a painful disease that can result in shortened lifespan if left untreated. The normal variant of the gene is designated as S and the affected gene as s. Individuals inherit variants of the gene (called alleles) each from their mother and father. If a person has SS (homozygous dominant), then they do not have the disease. If a person has the variants Ss (heterozygous), then they do not have the disease but are a carrier. Two copies of the variant ss (homozygous recessive), one from the father and one from the mother, cause sickle cell anemia. The variant ss causes the red blood cells to become sickle-shaped, preventing them from transporting oxygen.
Why would such a harmful mutation become so common in a population? Why wouldn’t it fade away if it was so deleterious? The answer is natural selection. People with the variants Ss, who are carriers of the disease, are also resistant to malaria, a zoonotic disease transmitted by mosquitoes. Those with the SS variants are not resistant. The Ss variants survive at a greater rate than SS. Sickle cell trait is prevalent in those areas where malaria is common like western Africa, the Arabian Peninsula, and southern India. Because western Africans were brought to the United States as slaves, sickle cell anemia is prevalent among African Americans as well. Blood tests can determine if someone is a carrier and ascertain the likelihood of transmitting the disease to offspring.
ss Homozygous recessive Sickle cell anemia
Skin Color
All primates can produce melanin in their skin, which is a natural sunscreen. Skin color depends on the type of melanin produced in skin cells called melanocytes. Melanin also affects what eye color you have. Blue eyes derive from a mutation in a genetic “switch” for the OCA2 gene (Eiberg 2008). The switch reduces the ability of the gene to produce melanin in the eye resulting in blue eyes. Melanin also colors animal hair and bird feathers. But why does human skin color differ?
Ultraviolet radiation damages DNA in the skin and disrupts cell processes. Dark skin protects against ultraviolet radiation and the mutations it can cause. Melanin acts as a barrier between the ultraviolet rays and the nucleus of the skin cell, which houses the DNA. In short, melanin protects DNA and helps prevents skin cancers. Those with dark skin in high UV regions, which correlates generally with latitude, would have a selective advantage over lighter-skinned people. But protecting DNA in skin cells is not the only advantage. Dark skin also conserves folate, which is destroyed by ultraviolet-B sunlight (UVB). Folate is essential because low folate in pregnant women can result in severe birth defects called neural tube defects. After all, the demand for folate increases during pregnancy. Thus, dark skin confers a great advantage over light skin in the tropics not just because it prevents skin cancers, but also because it prevents birth defects. These advantages would quickly make dark skin universal in areas of high UV, much like the dark fur on rock pocket mice on lava flows. Because folate is destroyed by sunlight, pregnant women take folic acid or eat foods high in folate to prevent neural tube defects. In the United States, many foods like cereals, bread, and pasta, are supplemented with folic acid for this reason.
We can then ask, why do some people have lighter skin? Lighter skin is a liability in the tropics, but those with lighter skin can better synthesize vitamin D (a hormone necessary for the absorption of calcium) in more northerly climates. Melanin greatly slows the production of vitamin D. A very dark-skinned person will take six times as long to produce the same amount of vitamin D as a light-skinned person. Nutritional rickets, a deforming bone disease, can develop in the presence of vitamin D deficiency. Women with rickets have reduced pelvic openings, and have difficulty delivering babies, making the selective factors for light skin strong in some areas. Some of the first c-sections in the U.S. were on enslaved African American women who suffered from pelvic deformities, likely brought about by vitamin D deficiencies. Foods are now enriched with vitamin D to prevent Vitamin D deficiencies (in the past, kids took cod liver oil). Vitamin D deficiencies are now being recognized as having other effects including a weakened immune system and an association with cancers. Like dark skin in the tropics, light skin is naturally selected for in areas of lower ultraviolet radiation.
There are still other skin phenotypes that are the product of natural selection. The ability to tan is also an adaptive trait based on genetic and environmental interaction. Tanning is the ability to increase melanin production when needed. In some areas of the world, the amount of sunlight varies considerably from one season to the next (e.g., the Mediterranean). Local populations have physiological mechanisms to darken their skin during yearly seasons of high sunlight. In other areas of the world, cloudy conditions prevail even during summer seasons and very little tanning ability has evolved (British Isles).
Biology and Destiny
All traits are genetic. Even if you spend hours at the gym and are ripped, that is still a genetic trait. How can that be? Genes produce chemicals that respond to all that iron pumping, ultimately creating big muscles. But all traits are also environmental. Wait, what? That’s right, the old nature-nurture debate has long been put to rest. For example, height has a genetic component, but diet also plays a role in how tall you will be. This is why people have become taller over the generations. Better nutrition and simply more food allow genes to reach their height potential. Superman is a good analogy. Under a red sun, he’s just your ordinary, mild-mannered, Clark Kent type. Under a yellow sun, he can fly and has x-ray vision. A yellow sun permits Superman’s genes to achieve their potential. This happens in other species as well. Himalayan rabbits raised in cold temperatures will have dark pigments on their nose, paws, and tail, and those raised at warmer temperatures are all white (Lobo, 2008). In this case, temperature affects whether a gene will be expressed or not. The temperature at which alligators are incubated determines whether they will be born male or female. Grasshoppers born into crowded conditions will have increased hopping ability, presumably to more easily migrate out of their current habitat. Genes and environment can’t be separated; instead, they interact to produce traits. Some traits, however, are more heritable than others, which means that the environment plays a lesser role in their expression. Rather than “nature versus nurture”, it is more accurate to speak of “nature through nurture.”
Sometimes the media portrays traits as purely genetic. For example, a non-mutated gene ACTN3 occurs in virtually all Olympic power athletes like sprinters and power-lifters (MacArthur 2008). The gene variant produces a protein that allows for fast muscle contraction. One company called ATLAS at one point even marketed to parents to identify children’s version of the gene, to direct their kids into the correct sport. But the gene, of course, isn’t near the whole story. First, like other complex traits, other genes also influence athletic ability (though they are still poorly understood). And environmental factors, namely diet, and high-level training, also affect athletic success. What if you have the fast-twitch gene, but sit in a cubicle all day? Will you still become an Olympic athlete? Not likely.
Jamaicans have high frequencies of the ACTN3 gene and have dominated sprinting in the Olympics. But, running is a national pastime in Jamaica, comparable to football in the United States. In fact, the gene is thought to predict just 2–3 percent of the muscle variation in the general population. To illustrate this point, Usain Bolt very likely has at least one fast-twitch allele for ACTN3, but so does your anthropology instructor. The presence of the variants of ACTN3 can’t be the whole story. Genes and environment work together. Studies vary widely, finding that ACTN3 only accounts for 0 to around 2 percent difference in sprinting speed (Lieberman 2021). In his book Exercised, Lieberman suggests that there are likely many genes that influence athletic ability, just as there are more than 400 genes that influence height. There is no single gene that accounts for running ability within populations or between populations (Lieberman 2021).
Race
Racial classification involves assigning humans to categories based on phenotype, especially traits that are outwardly apparent. In the recent past, American children were taught that there are 5 great races of the world, a taxonomy based on Johann Blumenbach’s racial hierarchy of the late 1790s. This is the essentialist view of race—that there are discrete groups with large gaps between them. According to Blumenbach, “Caucasians” were the most ideal form, and everyone was of a degenerate form of human.
The essentialist view of race runs into immediate problems in light of the continuous nature of traits, especially skin, hair, and eye color. Skin color and eye color are not straightforward SNPs like lactose tolerance or sickle cell trait. Rather, they are influenced by several different genes, more than 15 for skin and 16 or more for eye color. As a result, skin color can be “blended” in children of parents with different levels of skin pigmentation. Then, skin color is not an essentialist category, but rather a continuum. If skin color is meant to reflect deeper qualities of a person or a person’s wider genotype, what do we make of siblings, even fraternal twins, who are considered different races based on their skin color? And how does a single individual who shares perceived features of different races—like dark skin and blonde hair— get categorized? For instance, blonde hair arose independently in Europe and Melanesia. (In Melanesia the blonde trait is caused by a single SNP, a C switched to a T). How would these people be categorized based on phenotype? Which trait is considered more important to race, and why? People have to decide, culturally, whether someone belongs to a race or not.
During Blumenbach’s time, nothing was known about genetics. Augustinian friar Gregor Mendel (1822–1884), who began the study of genetics by working out the inheritance of pea plants, had not even been born. Instead, Blumenbach based his categories on his perception of phenotype and his own biases. Many today assume still that racial categories correspond to deep underlying genetic differences.
With the Human Genome Project results, we know more about the genotypes of human populations. For instance, we now know that the genetic variation between any two individuals is about .1 percent. Since we have 3 billion pairs of bases, that means about 3 million differences. Most genetic variation, SNPs, and other forms of mutation (85–95%) are found within populations—nations and linguistic groups— around the world. As writer Malik Kenan in “Why Both Sides are Wrong in the Race Debate” writes, “Imagine that some nuclear nightmare wiped out the entire human race apart from one small population—say, the Masai tribe in East Africa. Almost all the genetic variation that exists in the world today would still be present in that one small group.” A smaller percentage of genetic variation occurs between supposed races, about 3–5 percent. Maybe this 3 to 5 percent difference is useful for dividing up people? As Kenan points out, the differences between human populations are purely statistical, not essential or absolute. This means populations are more likely to contain certain alleles, but not everyone has them. Secondly, statistical differences could be found between virtually any two populations, such that there could theoretically be hundreds or thousands of races based on genetics if we decided that those categories would be useful and productive for society or science. If you’re looking for statistical genetic differences between populations, you will find them. Even if there are genetic differences between populations, complex traits like athleticism, intelligence, musicality, and so forth are not influenced by a few genes, but likely hundreds of genes as well as the environment. We always have to decide which criteria, whether phenotypic or genotypic, to base our categories, and also we need to consider why these categories are needed.
In another light, race is very much real even though as a biological category it has little value. Culturally, race is very much real. We know that we humans create our world—we decide that money, companies, borders, and so forth—are real things. The same is true for race. The great lengths to which people will go to create racial categories are enlightening. In the United States, for example, the one drop rule meant that any African ancestry qualified someone as being black, but not white, even if most of their ancestors were European and light-skinned. As a result, Barack Obama was the first black president of the United States, even though his anthropologist mother was considered white. Some racial categories are ridiculously specific. For example, Louisiana had several categories for people of African descent, including quadroon (¼ African), octoroon (⅛ African), and even hexadecaroon (1/16 African). In other cases, racial categories were explicitly cultural. Pilar Ossorio, legal scholar, microbiologist, and bioethicist writes:
“And historically, in order to be a naturalized citizen in this country, as an immigrant, you had to be categorized as white or black. So the courts had to make decisions about who was white and who was not. Is an Armenian person white? There were several cases dealing with Asian people, and are they white or not white. And so one of the things that would happen is the person would come into court and say, “Look, my skin color is as white as anybody else’s skin color in here who is categorized as white. The court often decided who was white and who wasn’t based on whether they felt that the person would politically fit well into the kind of society we were trying to build.”
Individuals have gone to great lengths to be recognized as a particular race. A 1970 law in Louisiana stated that 1/32 African-American genes qualified an individual as black. Susie Guillory Phipps, who considered herself white, discovered she was legally considered African American when she ordered a copy of her birth certificate. The Phipps family began a 20,000-dollar legal battle to get the law declared unconstitutional and to get Susie Phipps officially declared white.
Kim Tallbear (2014) explains how racial classification has affected tribal membership for native people: “In most US tribes, you have a specific blood quantum needed for enrollment – often one-quarter. That means you have to be able to show with paper documentation that you have one out of four grandparents who is full blood. Or you might have two grandparents who are half-blood – however, you can make those fractions work.” According to TallBear, some tribes have turned to DNA testing to determine who qualifies for membership. While genetic testing can determine paternity, no test can determine a genetic link to a particular tribe. Native identity is not racial, but rather, Tallbear argues, being culturally part of an indigenous community. Relying on biology as a qualification for tribal membership, she argues, means handing over control of tribal identity to genetic research institutions (Tallbear 2016).
Forensic Anthropology
Forensic anthropologists examine human remains to try to identify a deceased individual to be used as evidence in court. To achieve this, forensic anthropologists examine bones and sometimes DNA to estimate the individual’s stature, health, injuries, sex, age, how they lived, and outward appearance. Forensic anthropologists will also use cultural cues, like clothing, jewelry, and other effects, to aid in the identification. Work is often conducted with unidentified soldiers’ remains, mass graves, victims of terrorism, natural disaster victims, crime victims, and sometimes bodies in unmarked graves.
We know that race is not an essentialist category with all members of a perceived race having all genetic variants. However, there is a statistical likelihood of having characteristics if your ancestors were from a particular geographical area like Europe, Asia, or Africa. Forensic anthropologists use cranial measurements and a formula to estimate how similar the victim was to modern geographical populations. Based on these findings, the forensic anthropologist can estimate what social category the person would likely be classified as. If the victim’s ancestry is not very mixed, then the estimate will be more accurate. However, if the person’s ancestry is mixed, it will be very difficult to know how that person’s was viewed socially in terms of race.
https://www.nytimes.com/interactive/2017/05/04/us/texas-border-migrants-dead-bodies.html