The basis of population genetics is the Hardy-Weinberg law, which was formulated in a context of concern that a dominant trait would eventually displace a normal trait in the population. In particular, it arose in response to the fallacious assertion that if brachydactyly is a dominant trait then, “in the course of time, one would expect in the absence of counteracting factors to get three brachydactylous persons to one normal.
If the frequency of particular gene A is p, then its alternate allele a is (1 — p) = q; the population will consist of individuals of three genotypes: those who are homozygous AA, those who are heterozygous Aa, and those who are homozygous Aa. The frequency of these genotypes in a randomly mating population will be in the proportion p2 (AA), 2pq (Aa), and q2 (aa).
One important consequence of this formulation is that whatever the initial frequency of the genes A and a in the population, the proportion of the three genotypes will tend to remain constant during succeeding generations, providing that the three genotypes are equally fertile. If the mating in the population is not random or if there is not equal viability of the three genotypes, the frequency calculations require considerable adjustment and in small populations substantial changes in gene frequency may occur simply as a matter of chance.
A practical consequence of the Hardy-Weinberg law is that if the frequency of a certain rare recessive disease is known, the frequency of the abnormal gene as well as the frequency of heterozygous carriers can be calculated. For a recessive inherited disease aa (q2) with a frequency of 1 per 10,000, the frequency of the gene a (q) will be the square root of 1/10,000 or 1/100. The frequency of heterozygous carriers will be 2 x p X q= 2 x 99/100 x 1/100 or approximately 1/50. Thus, for this trait there will be 200 clinically normal carriers of the abnormal gene in the population for every affected individual. Cystic fibrosis of the pancreas has a frequency (q2) of approximately 1 in 2500; thus the frequency of heterozygous carriers is approximately 1 in 25 (2pq).
What Is Population Genetics What Does It Do
Mutation and Selection.
A mutation is a stable heritable change in the genetic material. This change may affect a single locus, or it may consist of chromosome breakage with loss or rearrangement of th6 fragments. In molecular terms, a point mutation can be regarded as an alteration, addition, or deletion of one of the bases of the DNA molecule. The effect of a mutation in a somatic cell is restricted to the life of an individual, whereas mutation in germ cells can be transmitted to future generations.
The natural mutation rate can be greatly increased by x-rays, ultraviolet rays, increased temperature, and various chemical mutagens such as nitrogen mustard, ethylene sulfonate, and 5-bromouracil. Chemical mutagens are thought to achieve their effects by direct structural modification of a purine or pyrimidine base, or by substitution of a base analogue for one of the normal bases.
The germinal mutation rate is usually expressed as the number of mutations per locus per generation. Present estimates of spontaneous mutation rates for a number of traits vary between 0.5 x 10-5 and 10 x 10~5. One common, often unavoidable, error in estimating mutation rates in man is the failure to recognize that indistinguishable clinical syndromes can be caused by different genes (see Genetic Heterogeneity).
Thus, the frequencies deduced by the elegant studies of Haldane on mutation rate for hemophilia must be revised downward because Christmas disease, another bleeding trait on the X-chromosome, had not been discovered when the original calculations were made. Hurler’s syndrome (gargoylism) is an example of a disease that, because it can be caused by a gene on the X-chromosome or by one on an autosomal, requires an estimate of the mutation rate for each gene. Non hereditary conditions which mimic mutations are termed photocopies and also lead to overestimation of mutation rates.The frequency of most genes in the population is relatively stable. When a gene is rare and severely disadvantageous, the mutation rate is balanced by the elimination of the disadvantageous disadvantageous gene by natural selection.
The frequency of the disadvantageous gene, however, can be stabilized at a high level if the heterozygotes are slightly favored and leave a greater number of progeny than either homozygous (balanced polymorphism). An example of such a balance is the increased resistance of individuals heterozygous for sickle-cell trait to falciparum malaria. Although patients with sickle-cell disease (homozygous) usually die before they can reproduce; and thus cannot transmit the gene to the next generation, the incidence of the sickle-cell trait may reach 40 per cent in certain West African populations.
Theoretically, the high frequency of the sickle-cell gene could be maintained if the heterozygote were 25 per cent more fit than the so-called normal homozygote. It has now been shown unequivocally that death from falciparum malaria is much less frequent in carriers of the sickle-cell trait than in non carriers, and thus the heterozygote does have an advantage. How much of the advantage is due to differential mortality and how much to differential fertility is uncertain, but this example serves to emphasize that the effect of genes can be assessed only in relation to a particular environment.
Muller introduced the term genetic load to describe the total genetic disability of a population. It is composed of “the mutational load, the load due to recurrent mutations from a normal to a lethal or sublet gene, and the segregation load, which is due to the segregation of harmful genes from favorable heterozygotes. The sickle-cell gene is maintained in the population because of its heterozygous advantage, and thus contributes to the segregation load. It has been estimated that, on the average, every person has three to six genes that, if homozygous instead of heterozygous, would be lethal. The relative contribution of the segregation and mutational load to the total load is unsettled.
