60 6.2 Genetic Variation

Created by: CK-12/Adapted by Christine Miller

Figure 6.2.1 Phenotypic variation is a great reason to jump for joy!

Jumping for Joy!

The people in Figure 6.2.1 illustrate some of the great phenotypic variation displayed in modern Homo sapiens. The lighter-skinned men in the photo are Euro-American tourists in Kenya (East Africa). The darker-skinned men are native Kenyans who belong to a tribal group named the Maasai. These men come from populations on different continents on opposite sides of the globe. Their populations have unique histories, environments, and cultures. Besides differences in skin colour, the men have different hair and eye colours, facial features, and body builds. Based on such obvious physical differences, you might think that our species is characterized by a high degree of genetic variation. In fact, there is much less genetic variation in the human species than there is in many other mammalian species, including our closest relatives — the chimpanzees.

Overview of Human Genetic Variation

No two human individuals are genetically identical unless they are monozygotic (identical) twins. Between any two people, DNA differs, on average, at about one in one thousand nucleotide base pairs. We each have a total of about three billion base pairs, so any two people differ by an average of about three million base pairs. That may sound like a lot, but it’s only 0.1% of our total genetic makeup. This means that two people chosen at random are likely to be 99.9 per cent identical genetically, no matter where in the world they come from.

At an individual level, most human genetic variation is not very important biologically, because it has no apparent adaptive significance. It neither enhances nor detracts from individual fitness. Only a small percentage of DNA variations actually occur in coding regions of DNA — which are sequences that are translated into proteins — or in regulatory regions, which are sequences that control gene expression. Differences that occur in other regions of DNA have no impact on phenotype. Even variations in coding regions of DNA may or may not affect phenotype. Some DNA variations may alter the amino acid sequence of a protein, but not affect how the protein functions. Other DNA variations do not even change the amino acid sequence of the encoded protein.

At a population level, genetic variation is crucial if evolution is to occur. Genetically-based differences in fitness among individuals are the key to evolution by natural selection. Without genetic variation within populations, there can be no differential fitness by genotype, and natural selection cannot occur.

Patterns of Human Genetic Variation

Data comparing DNA sequences from around the world show that only about ten per cent of our total genetic variation occurs between people from different continents, like the American tourists and African Maasai pictured in Figure 6.1.1. The other 90 per cent of genetic variation occurs between people within continental populations, such as between North Americans or between Africans. Within any human population, many genes have two or more normal alleles that contribute to genetic differences among individuals. The case in which a gene has two or more alleles in a population at frequencies greater than one per cent is called a polymorphism. A single nucleotide polymorphism (SNP) involves variation in just one nucleotide in a DNA sequence. SNPs account for most of our genetic differences. Other types of variations (such as deletions and insertions of nucleotides in DNA sequences) account for a much smaller proportion of our overall genetic variation.

Different populations may have different allele frequencies for polymorphic genes. However, the distribution of allele frequencies in different populations around the world tends not to be discrete or distinct. Instead, the pattern is more often one of gradual geographic variations, or clines, in allele frequencies. You can see an example of a clinal distribution of allele frequencies in the map (Figure 6.2.2) below. Clinal distributions like this may be a reflection of natural selection pressures varying continuously over geographic space, or they may reflect a combination of genetic drift and gene flow of neutral alleles.

Example of clines in allele frequencies
Figure 6.2.2 This map shows the Old World clinal distribution of a single nucleotide polymorphism. The inset map focuses on the Indian subcontinent in South Asia. The red dots are locations where samples were collected. The numbers on the X-axis are allele frequencies.

Although most genetic variation occurs within rather than between populations, certain alleles do seem to cluster in particular geographic areas. One example happens with the Duffy gene. Variations in this gene are the basis of the Duffy blood group, which is determined by the presence or absence of a red blood cell antigen, similar to the more familiar ABO blood group antigens. The genotype for having no antigen for the Duffy blood group is far higher in African populations and in people who have African ancestry than it is in non-African people, as indicated in the following table. Genes (such as the Duffy gene) may be useful as genetic markers to establish the ancestral populations of individuals.

Table 6.2.1

Population Frequencies for No Antigen in the Duffy Blood Group

Population Frequencies for No Antigen in the Duffy Blood Group
Population Per cent of Population Lacking Duffy Antigen
African 88-100
African American 68
non-African American <1

The reason for the different population frequencies for the Duffy antigen appears to be natural selection. People who lack the Duffy antigen are relatively resistant to malaria, which is one of the oldest and most devastating human diseases. Malaria has been a persistent and widespread disease in sub-Saharan Africa for tens of thousands of years. DNA analyses suggest that the allele associated with lack of the Duffy antigen evolved at least twice in Africa and was strongly selected for, causing it to increase in frequency. The Duffy gene is just one of many genes that have polymorphic alleles, because one of the alleles protects against malaria. In fact, a greater number of known genetic polymorphisms may be attributed to selection because of malaria than any other single selective agent.

Factors Influencing the Level of Human Genetic Variation

The age and size of a population increases the genetic variation within that population. You would expect an older, larger population to have more genetic variation. The older a population is, the longer it has been accumulating mutations. The larger a population is, the more people there are in which mutations can occur. Anatomically modern humans evolved less than a quarter million years ago, which is a relatively short period of time for mutations to accumulate. Our population was also quite small at some point in the past, perhaps consisting of no more than ten thousand adults, which reduced genetic variation even more. These factors explain why humans are relatively homogeneous genetically as a species.

What We Can Learn From Knowledge of Human Genetic Variation

Knowledge of genetic variation can help us understand our similarities and differences, our origins, and our evolutionary past. It can also help us understand human diseases and — hopefully — find new ways to treat them.

Human Origins

The data on human genetic variation generally supports the out-of-Africa hypothesis for human origins. According to this hypothesis, the common ancestor of all modern humans evolved in Africa around 200 thousand years ago. Then, starting no later than about 60 thousand years ago, part of the African population left Africa and migrated to Europe and Asia. As the migrants spread throughout the Old World, they replaced (and/or absorbed) the populations of archaic humans they encountered.

Most studies of human genetic variation find there is greater genetic diversity in African than non-African populations. This is consistent with the older age of the African population proposed by the out-of-Africa hypothesis. In addition, most of the genetic variation in non-African populations is a subset of the variation in African populations. This is consistent with the idea that part of the African population left Africa much later and migrated to other places in the Old World.

Recent comparisons of modern human and archaic human (including Neanderthal and Denisovan) DNA show that interbreeding occurred between their populations, but to differing degrees. The result of new DNA sequences entering a population’s gene pool through interbreeding is called admixture. There is greater admixture with archaic humans in modern European, Asian, and Oceanic populations than in modern African populations. Populations with the greatest admixture are those in Melanesia. About eight per cent of their DNA came from archaic Denisovans in East Asia.

Human Population History

Patterns of human genetic variation can be used to reconstruct population history. That history is literally recorded in our DNA. Any major population event (such as a significant reduction in population size or a high rate of migration) leaves a mark on a population’s genetic variation.

  • Going through a dramatic size reduction decreases intra-population genetic variation (variation occurring within a population). As a case in point, DNA analyses suggest that there may have been drastic size reductions in the human populations that colonized the New World between 15 thousand and 20 thousand years ago. There were also size reductions in the human populations that first left Africa at least 60 thousand years ago, which helps explain the lower genetic diversity of modern non-African populations.
  • A high rate of migration between populations may lead to gene flow, and this changes genetic variation in two ways. Gene flow decreases inter-population genetic variation (variation occurring between populations), while it increases intra-population variation. Gene flow — primarily between nearby populations — may contribute to the formation of clines in allele frequencies, as on the map in Figure 6.2.2.

Human Genetic Variation and Disease

An important benefit of studying human genetic variation is that we can learn more about the genetic basis of human diseases. The more we understand the causes of diseases, the more likely it is that we will be able to find effective treatments and cures for them.

Some disorders are caused by mutations in a single gene. Most of these disorders are generally rare, but some of them occur at significantly higher frequencies in certain populations. For example, Ellis-van Creveld syndrome has an unusually high frequency in Pennsylvania Amish populations, and Tay-Sachs disease has a relatively high frequency in Ashkenazi Jewish populations. Albinism is another single-gene disorder that has a variable frequency. In North America and Europe, rates of albinism are approximately 1:18,000. In Africa, in contrast, the rates range from 1:5,000 to 1:15,000. Some African populations have estimated albinism rates as high as 1:1000. The photo below (Figure 6.2.3) shows an African albino man from Mali, where there is a relatively high rate of albinism. High population-specific frequencies of single-gene disorders like these may be attributable to a variety of factors, such as small founding populations and a relative lack of gene flow.

Example of a human displaying albinism
Figure 6.2.3 This man from Mali exhibits the lack of pigmentation that is a hallmark of albinism.

It is likely that the majority of human diseases are caused by a complex mix of multiple genes (polygenic) and environmental factors (multifactorial). Examples of polygenic, multifactorial diseases are type II diabetes and heart disease. We do not typically think of these diseases as genetic diseases, because our genes do not predetermine whether we develop them. Our genes, however, do influence our chances of developing the diseases under certain environmental conditions. Even our chances of developing some infectious diseases are influenced by our genes. For example, a variant allele for a gene called CCR5 seems to confer resistance to infection with HIV, the virus that causes AIDS.

6.2 Summary

  • No two human individuals are genetically identical (except for monozygotic twins), but the human species as a whole exhibits relatively little genetic diversity, relative to other mammalian species. Genetically, two people chosen at random are likely to be 99.9 per cent identical.
  • Of the total genetic variation in humans, about 90 per cent occurs between people within continental populations. Only about 10 per cent occurs between people from different continents. Older, larger populations tend to have greater genetic variation, because there is more time and there are more people in which to accumulate mutations.
  • Single nucleotide polymorphisms account for most human genetic differences. Allele frequencies for polymorphic genes generally have a clinal (rather than discrete) distribution. A minority of alleles seem to cluster in particular geographic areas, such as the allele for no antigen in the Duffy blood group. Such alleles may be useful as genetic markers to establish the ancestry of individuals.
  • Knowledge of genetic variation can help us understand our similarities and differences. It can also help us reconstruct our evolutionary origins and history as a species. For example, the distribution of modern human genetic variation is consistent with the out-of-Africa hypothesis for the origin of modern humans.
  • An important benefit of studying human genetic variation is learning more about the genetic basis of human diseases. This, in turn, should help us find more effective treatments and cures.

6.2 Review Questions

  1. Compare and contrast the significance of genetic variation at the individual and population levels.
  2. Describe genetic variation within and between human populations on different continents.
  3. Explain why allele frequencies for the Duffy gene may be used as a genetic marker for African ancestry.
  4. Identify factors that increase the level of genetic variation within populations.
  5. Discuss genetic evidence that supports the out-of-Africa hypothesis of modern human origins.
  6. What evidence suggests that modern humans interbred with archaic human populations after modern humans left Africa?
  7. How do population size reductions and gene flow impact the genetic variation of populations?
  8. Describe the role of genetic variation in human disease.
  9. Explain the reasons why variation in a DNA sequence can have no effect on the fitness of an individual.
  10. Explain why migration between populations decreases inter-population genetic variation. How does this relate to the development of clines in allele frequency?
  11. The amount of mixing of modern human DNA and archaic human DNA is an example of  _________ .

6.2 Explore More

The Journey of Your Past | National Geographic, National Geographic, 2013.


Svante Pääbo: DNA clues to our inner neanderthal, TED, 2011.

Why Are Some People Albino?, Seeker, 2015.



Figure 6.2.1

Maasai_men_and_tourists_jumping by Christopher Michel on Wikimedia Commons is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0/deed.en) (license.

Figure 6.2.2

Geospatial_distribution_of_SNP_rs1426654-A_allele by Basu Mallick C, Iliescu FM, Möls M, Hill S, Tamang R, Chaubey G, et al. on Wikimedia Commons is used under a  CC BY 2.5 (https://creativecommons.org/licenses/by/2.5/deed.en) license.

Figure 6.2.3

Mali_Salif_Keita2_400 [cropped] by unknown from The Department of State, Washington, DC. on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain).


Basu Mallick C., Iliescu, F.M., Möls, M., Hill, S., Tamang, R., Chaubey, G., et al. (2013). The light skin allele of SLC24A5 in South Asians and Europeans shares identity by descent: Figure 2. Isofrequency map illustrating the geospatial distribution of SNP rs1426654-A allele across the world. PLoS Genetics, 9(11): e1003912. doi:10.1371/journal.pgen.1003912 http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003912

HealthLinkBC. (2019, November 5). Health topics: Malaria [online article]. BC Government (gov.bc.ca). https://www.healthlinkbc.ca/health-topics/hw119119

Mayo Clinic Staff. (n.d.). Albinism [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/albinism/symptoms-causes/syc-20369184

Mayo Clinic Staff. (n.d.). Heart disease [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/heart-disease/symptoms-causes/syc-20353118

Mayo Clinic Staff. (n.d.). HIV/AIDS [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/hiv-aids/symptoms-causes/syc-20373524

Mayo Clinic Staff. (n.d.). Type 2 diabetes [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/symptoms-causes/syc-20351193

National Geographic. (2013, March 13). The journey of your past | National Geographic. YouTube. https://www.youtube.com/watch?v=RGtaq3PiIoU&feature=youtu.be

National Institutes of Health/ National Library of Medicine. (n.d.). Genes: CCR5 gene – C-C motif chemokine receptor 5 [online article]. US Government. https://ghr.nlm.nih.gov/gene/CCR5

National Organization for Rare Disorders (NORD). (2012). Ellis Van Creveld syndrome [online article]. RareDiseases.org. https://rarediseases.org/rare-diseases/ellis-van-creveld-syndrome/

National Organization for Rare Disorders (NORD). (2017). Tay Sachs disease [online article]. RareDiseases.org. https://rarediseases.org/rare-diseases/tay-sachs-disease/

Seeker. (2015, July 25). Why are some people albino?. YouTube. https://www.youtube.com/watch?v=cHRM2S_fBOk&feature=youtu.be

TED. (2011, August 30). Svante Pääbo: DNA clues to our inner neanderthal. YouTube. https://www.youtube.com/watch?v=kU0ei9ApmsY&feature=youtu.be

Wikipedia contributors. (2020, June 18). Melanesia. In Wikipedia. https://en.wikipedia.org/w/index.php?title=Melanesia&oldid=963224885

Wikipedia contributors. (2020, June 4). Old world. In Wikipedia. https://en.wikipedia.org/w/index.php?title=Old_World&oldid=960713597






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Human Biology Copyright © 2020 by Christine Miller is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.

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