{"id":4632,"date":"2019-06-24T13:40:55","date_gmt":"2019-06-24T13:40:55","guid":{"rendered":"https:\/\/pressbooks.ccconline.org\/acchumanbio\/chapter\/8-2-genetic-variation-3\/"},"modified":"2023-11-30T18:46:06","modified_gmt":"2023-11-30T18:46:06","slug":"8-2-genetic-variation-3","status":"publish","type":"chapter","link":"https:\/\/pressbooks.ccconline.org\/acchumanbio\/chapter\/8-2-genetic-variation-3\/","title":{"raw":"6.2\u00a0Genetic Variation","rendered":"6.2\u00a0Genetic Variation"},"content":{"raw":" \r\n\r\n[caption id=\"attachment_2631\" align=\"aligncenter\" width=\"400\"]\"\" Figure 6.2.1 Phenotypic variation is a great reason to jump for joy!<\/em>[\/caption]\r\n

Jumping for Joy!<\/h1>\r\nThe people in Figure 6.2.1 illustrate some of the great phenotypic variation displayed in modern Homo sapiens.<\/em> 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<\/em>\u00a0genetic variation in the human species than there is in many other mammalian species, including our closest relatives \u2014 the chimpanzees.\r\n
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Overview of Human Genetic Variation<\/h1>\r\n<\/div>\r\nNo two human individuals are genetically identical unless they are [pb_glossary id=\"2632\"]monozygotic[\/pb_glossary] (identical) twins. Between any two people, [pb_glossary id=\"277\"]DNA[\/pb_glossary] 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.\r\n\r\nAt 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 \u2014 which are sequences that are translated into [pb_glossary id=\"5813\"]proteins[\/pb_glossary] \u2014 or in regulatory regions, which are sequences that control gene expression. Differences that occur in other regions of DNA have no impact on [pb_glossary id=\"2477\"]phenotype[\/pb_glossary]. Even variations in coding regions of DNA may or may not affect phenotype. Some DNA variations may alter the [pb_glossary id=\"5707\"]amino acid[\/pb_glossary] 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.\r\n\r\nAt 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 [pb_glossary id=\"2633\"]natural selection[\/pb_glossary] cannot occur.\r\n

Patterns of Human Genetic Variation<\/h2>\r\nData 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 [pb_glossary id=\"5449\"]alleles[\/pb_glossary] 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 [pb_glossary id=\"2634\"]polymorphism[\/pb_glossary].<\/strong>\u00a0A\u00a0[pb_glossary id=\"2635\"]single nucleotide polymorphism[\/pb_glossary] (SNP)<\/strong>\u00a0involves 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 [pb_glossary id=\"518\"]nucleotides[\/pb_glossary]\u00a0in DNA sequences) account for a much smaller proportion of our overall genetic variation.\r\n\r\nDifferent populations may have different [pb_glossary id=\"5449\"]allele[\/pb_glossary] 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\u00a0[pb_glossary id=\"5947\"]clines[\/pb_glossary],<\/strong> 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.\r\n\r\n[caption id=\"attachment_2637\" align=\"aligncenter\" width=\"748\"]\"Example 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.<\/em>[\/caption]\r\n\r\n
\r\n\r\nAlthough most genetic variation occurs <\/span>within<\/em>\u00a0rather than\u00a0<\/span>between<\/em> 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 <\/span>table. Genes (such as the Duffy gene) may be useful as genetic markers to establish the ancestral populations of individuals.<\/span>\r\n\r\nTable 6.2.1<\/strong>\r\n\r\nPopulation Frequencies for No Antigen in the Duffy Blood Group<\/em>\r\n\r\n\r\n\r\n\r\n\r\n
Population Frequencies for No Antigen in the Duffy Blood Group<\/strong><\/caption>\r\n
Population<\/strong><\/td>\r\nPer cent of Population Lacking Duffy Antigen<\/strong><\/td>\r\n<\/tr>\r\n
African<\/td>\r\n88-100<\/td>\r\n<\/tr>\r\n
African American<\/td>\r\n68<\/td>\r\n<\/tr>\r\n
non-African American<\/td>\r\n<1<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n<\/div>\r\nThe 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<\/a>, 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,\u00a0causing 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.\r\n

Factors Influencing the Level of Human Genetic Variation<\/h2>\r\nThe 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.\r\n
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What We Can Learn From Knowledge of Human Genetic Variation<\/h1>\r\n<\/div>\r\nKnowledge 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 \u2014 hopefully \u2014 find new ways to treat them.\r\n

Human Origins<\/h2>\r\nThe 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<\/a>, they replaced (and\/or absorbed) the populations of archaic humans they encountered.\r\n\r\nMost 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.\r\n\r\nRecent comparisons of modern human and archaic human (including [pb_glossary id=\"2638\"]Neanderthal[\/pb_glossary] and [pb_glossary id=\"2639\"]Denisovan[\/pb_glossary]) DNA show that interbreeding occurred between their populations, but to differing degrees. The result of new DNA sequences entering a population\u2019s gene pool through interbreeding is called\u00a0[pb_glossary id=\"5865\"]admixture[\/pb_glossary].<\/strong>\u00a0There 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<\/a>. About eight per cent of their DNA came from archaic Denisovans in East Asia.\r\n

Human Population History<\/h2>\r\nPatterns 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\u2019s genetic variation.\r\n