Textbook Assignment: This lecture assembles a few highlights that are not fully synchronized with the textbook. See page numbers under "major concepts", below. Note that this and the previous lecture together cover all of chapter 24 except multiple alleles and sex-linked genes (pages 663-665), and also the material in chapter 25 on genetic variation (pages 688-691). The boxed articles on eugenics (pages 676-677) and heritability of human IQ (pages 654-655), and the introductory discussion of eugenics on pages 10-11 should also be read for this lecture.
Major concepts
Relative fitness: The relative fitness of different genotypes can be defined as the relative ability of each genotype to pass its alleles on to future generations. Relative fitness is designated as W. The highest relative fitness value is generally assumed to be 1.0 and others expressed as fractions of that value. Thus, if genotype AA has a fitness of W = 1.0, an alternative genotype aa that yields half as many successful progeny per generation would have a relative fitness of W = 0.5.
Selection coefficient: An alternative expression for the same phenomenon is the selection coefficient, s, which is favored in our current textbook. The s value indicates how much selection there is against a particular genotype. An s value of zero indicates maximum fitness, with 100% of the population surviving to reproduce, a value never realized in a real population. At the other extreme, an s value of 1.0 indicates that individuals with that particular genotype never survive to reproduce. If the selection is only against a homozygous recessive genotype with s = 1 and not against heterozygotes, most of the recessive alleles will be present in the population in heterozygous individuals, such that the complete elimination of the allele will be a slow process (figure 24.13 and 24.14).
Balance between mutation and selection: If a dominant phenotype has the highest relative fitness, selection will tend to fix the dominant allele in the population. If new recessive alleles are continually arising by mutation, the equilibrium value in the population will reflect a balance between rate of creation of new alleles by mutation and their elimination by selection, and may result in retention of a significant level of the allele in the population, carried primarily by heterozygotes, with homozygous recessives being rare.
Changing environmental conditions: It is important to recognize that relative fitness can change sharply with changing environmental conditions (e.g. introduction of new predators, diseases, modification of habitat by natural disaster or manmade effects, etc.). One example illustrated in the book is the relatively recent selective change that now favors darker colors in the English peppered moth, Biston betularia. The environmental change that altered the selective pattern in this case was the darkening of tree bark by industrial soot which provided a selective advantage to moths with darker protective coloration (Figure 24.15). See Lecture 7 notes for a brief discussion of the alleles that are involved in these changes.
Heterozygote advantage: If a heterozygous genotype has the highest relative fitness, the population will reach an equilibrium with the heterozygote stabilized. One example of heterozygote advantage that we have touched on before is sickle cell anemia in parts of Africa. Because the electrophoretic patterns of normal beta globin and the sickle-cell mutation are expressed codominantly, it is relatively easy to identify both types of homozygotes, as well as heterozygous individuals. In the absence of modern medical intervention, the sickle cell heterozygote is far more viable in malaria-infested areas than either of the homozygotes. The sickle cell homozygotes die young of sickle cell disease, and the "normal" homozygotes tend to die from malaria. The heterozygotes do not exhibit the recessive sickle cell disease, but are resistant to malaria, and thus form the healthy population that is responsible for most of the reproduction. Despite loss of 1/4 of their children to sickle cell disease and up to 1/4 to malaria, they are able to maintain a viable population of reproducing heterozygotes. (Please note that the above is an exaggeration for clarity, since the loss of normal homozygotes to malaria is not 100%. Nevertheless, the allelic frequency for HbS may be as high as 12.5% in some areas. This corresponds to over 20% heterozygous (2 x .125 x .825) and about 1.6% homozygous for sickle cell anemia (.125 x .125). Calculations based on relative fitness values for the three genetic classes yield similar results.
Polymorphic loci: A genetic locus is considered to be polymorphic if it has two or more known alleles and if the allelic frequency of any one allele does not exceed 0.99. Loci with a single allele at a frequency of 0.99 or greater are considered to be monomorphic. Most species exhibit relatively high frequencies of polymorphic loci (20-40%). However, certain species such as the Northern elephant seal and the cheetah exhibit almost no polymoprhic loci. A low level of polymorphic loci generally is the result of a bottleneck situation (described below) in which a very low surviving population expanded to give rise to the current larger population. Absence of genetic variability makes a species extremely vulnerable to environmental changes (such as new diseases) that could uniformly affect the entire population. There is also a risk that deleterious genes may become fixed in the population due to genetic drift during the bottleneck period (pages 688-691; see also discussion of inbreeding depression and hybrid vigor on pages 675-676).
Heterozygosity: The frequency of occurrence of the heterozygous state at a particular locus is called hererozygosity, (H). In the absence of any distorting forces, H = 2pq, as predicted by the Hardy-Weinberg relationship
However, distorting forces, such as inbreeding and genetic drift often reduce the actual observed heterozygosity (H) to a value that is less that the theoretical prediction of 2pq.
Average heterozygosity is determined by averaging the H values for a number of separate loci, including those that have no heterozygosity. It looks at the extent of heterozygosity in a population, as opposed to the number of different loci that exhibit some degree of heterozygosity due to polymorphism.
Bottlenecks: As indicated above, an evolutionary bottleneck refers to a time when a population was reduced to very small numbers before recovering. In the case of the northern elephant seal, the bottleneck resulted from being hunted almost to extinction before the population recovered after hunting was banned. The cause of the apparent bottleneck in the evolutionary history of the cheetah remains unknown.
Effect of bottlenecks: Two types of distortion of the Hardy-Weinberg equilibrium are likely to result from bottlenecks. The first is increased homozygosity due to increased levels of inbreeding that are almost inevitible when the total population is small. This phenomenon was described in the previous lecture. The second is the so-called founder effect, which results from the chance inclusion of certain alleles in the small founder population, as described below..
Founder effect: One of the potential consequences of a bottleneck is a high frequency of recessive genetic diseases in the population resulting from one of the founders happening to be a carrier of a relatively rare disease whose heterozygote frequency is much higher than its homozygous frequency. The founder effect is based on the fact that a small sample may differ substantially in composition from the larger population it is drawn from, purely by random "sampling errors". You may recall as an example, the very large family group in Venezuela with a high incidence of Huntington disease that could be traced back to a single European immigrant (Lecture 31). In addition, founder effects can become further established in small populations by genetic drift as described below.
Genetic drift: Another problem that is encountered in small populations is genetic drift. Each new generation is a small sampling of all possible gametes and therefore may not be representative of the overall gene poos, again due to random sampling error. Numerous computer simulations have been done to show that allelic frequencies can drift away from original values as a result of the sampling error. If a population starts with p = q = 0.5, sampling may push the next generation to p = 0.6 and q = 0.4. The next generation may maintain this new ratio, or cause it to move again in either direction. In some cases, several moves in the same direction result in p = 1.0 and q = 0, after which the population is homozygous for p. Because subsets that become fixed as all p or all q cannot drift back, over time more and more of the isolated small populations will become homozygous. Thus, in addition to inbreeding and founder effects, a population that goes through a bottleneck and stays small for a while may become more homozygous through genetic drift (see pages 672-673)
Evolutionary dead ends: Variability provides the basis for natural selection as environmental conditions change. Even if a species is very well adapted to its current environment, it is at risk if it lacks variability (usually expressed as degree of heterozygosity or as fraction of polymorphic loci in the population). Environments do not stay constant. Many variables affect survival in an environment, including the introduction of new competing species, new predators, and new diseases. Disease is probably one of the major driving forces of evolution, although it is not yet as well recognized in that role as it should be. An epidemic that leaves only a few survivors may greatly alter the future gene pool in ways that have nothing directly to do with resistance to the disease (through founder effects, inbreeding of the survivors, and genetic drift). If a species lacks genetic diversity, it is in great danger of not having the resources to survive the next major environmental change and thus of becoming extinct.
Eugenics: The term eugenics was coined by a quantitative geneticist, Francis Galton, in 1883, well before the rediscovery of Mendel, and at a time when "blending" theories of heredity were still quite popular. The basic concept was based on Darwinian evolutionary theory and the assumption that the human species could be improved by encouraging higher levels of reproduction among the gifted and talented (positive eugenics) and restricting reproduction of individuals displaying less favorable characteristics (negative eugenics). In some ways, this can be viewed as an extension to humans of some of the principles used to improve domestic animals and crop plants. In addition, it is in some ways an attempt to apply the principles of population genetics to a human population, although it was started well before the principles of population genetics had been formalized mathematically.
Negative aspects of the eugenics movement" Early in this century, there was a strong and mostly very negative eugenics movement in the United States. Starting in 1907, numerous state laws began to require sterilization of "genetically inferior" individuals of various types, including the "feeble-minded", and in 1924, immigration from a number of countries in Eastern Europe and Asia was severely restricted because of perceived mental inferiority of immigrants from those countries. The most extreme abuses of eugenics occurred in Germany during the 1930's and early 1940's when the Nazis sought to erradicate certain ethnic groups they considered to be inferior.
The failure of eugenics: Even before those extremes turned many people away from the basic concept of eugenics, numerous leading geneticists had begun to challenge the premises it was organized around, as discussed in the boxed article on pages 676-677 and the introductory discussion of eugenics on pages 10-11 of our textbook. Among other things, there was a gradually growing realization that variability in a population plays an important role in long-term survival and that a high level of homozygosity is extremely dangerous to a population, as discussed earlier in this lecture. In addition, a better understanding of the complexity of inheritance of many traits and the interplay between heredity and environment made it clear that some of the policies were both unfair and incapable of achieving their goals. Thus, for example, elimination of individuals afflicted with homozygous recessive diseases did very little to rid the population of the disease alleles, which were carried primarily in disease-free heterozygous individuals.
Human intelligence: One of the goals of the eugenics movement was to reduce the number of "genetically feeble-minded" individuals in the population. As described in the boxed article on pages 676-677, the process of measurement of human intelligence and the role of heredity in determining the outcome of that measurement are both highly controversial topics. The current concensus is that IQ has a heritability of about 0.6. This observation continues to be used by some individuals to suggest that low performance by students from disadvantaged backgrounds is largely genetic and that attempted social or educational intervention is doomed to failure.
Inappropriate conclusions: The boxed article summarizes several fallacies in such conclusions. First, heritability applies to differences within a population, and does not say anything about individuals. Second, heritability cannot be used to compare populations (and thus to conclude that one of them is inferior). Third, heritability applies only to the population under the conditions when it was studied, and does not say anything about whether the mean level of achievement can be increased for the entire population by environmental changes. Thus, Klug and Cummings conclude that heritability must never be used as a biological justification for discriminatory social policies.
Euphenics: With a modern understanding of genetics and medicine, today's emphasis is far more on reducing the phenotypic manifestations of disease genes through procedures such as administration of insulin to diabetics. However, there is still some degree of eugenic intervention through prenatal diagnosis and early termination of pregnancies that would result in severe birth defects or birth of infants with uncurable genetic diseases.