1. Medical Genetics 08 基因变异的群体行为 Population Genetics

2. Medical Genetics

4. What is a population from a genetic perspective? A population in the genetic sense, is not just a group of individuals, but a breeding group

5. Medical Genetics The genetics of a population is concerned not only with the genetic constitution of the individuals but also with the transmission of the genes from one generation to the next.

6. Medical Genetics In the transmission the genotypes of the parents are broken down and a new set of genotypes is constituted in the progeny, from the genes transmitted in the gametes. The genes carried by the population thus have continuity from generation to generation, but the genotypes in which they appear do not. The genetic constitution of a population, referring to the genes it carries, is described by the array of gene frequencies, that is by specification of the alleles present at every locus and the numbers or proportions of the different alleles at each locus."

7. Medical Genetics Goals of Population Genetics 1.To describe how the frequency of an allele which controls a trait changes over time ； 2.To analyze the factors that lead to changes in gene (allele) frequencies ； 3.To determine how changes in gene (allele) frequencies affect evolution and speciation.

8. Medical Genetics Why Study Populations and Gene Frequencies 1.Genetic variability necessary for evolutionary success; 2.Measuring genetic variability at many loci can characterize a population; 3.Variability of phenotypic and molecular traits are analyzed.

9. Medical Genetics 1. Variability and Gene (or Allelic) Frequencies 1.Genetic data for a population can be expressed as gene or allelic frequencies; 2.All genes have at least two alleles; 3.Summation of all the allelic frequencies for a population can be considered a description of the population; 4.Frequencies can vary widely among the alleles in a population; 5.Two populations of the same species do not have to have the same allelic frequencies.

10. Medical Genetics Genotypic frequencies It describes the distribution of genotypes in a population.

11. Medical Genetics Example Blood type locus; two alleles, M or N, and three MM, MN, NN genotypes are possible (the following data was collected from a single human population).

12. Medical Genetics Genotye# of IndividualsGenotypic Frequencies MM1787MM=1787/6129=0.289 MN3039MN=3039/6129=0.50 NN1303NN=1303/6129=0.21 Total6129

13. Medical Genetics Deriving Gene (or Allelic) Frequencies To determine the allelic frequencies we simply count the number of M or N alleles and divide by the total number of alleles. f(M) = [(2 x 1787) + 3039]/12,258 = 0.5395 f(N) = [(2 x 1303) + 3039]/12,258 = 0.4605 By convention one of the alleles is given the designation p and the other q. Also p + q = 1. p=0.5395 and q=0.4605 Furthermore, a population is considered by population geneticists to be polymorphic if two alleles are segregating and the frequency of the most frequent allele is less than 0.99.

14. Medical Genetics Deriving allelic frequencies from genotypic frequencies The following example will illustrate how to calculate allelic frequencies from genotypic frequencies. It will also demonstrate that two different populations from the same species do not have to have the same allelic frequencies.

15. Medical Genetics Let: p=f(M) and q=f(N) Thus: p=f(MM) + ½ f(MN) and q=f(NN) + ½ f(MN).. PercentAllelic Frequencies LocationMMMNNNpq Greenland83.515.6 0.900.9130.087 Iceland31.251.517.300.5690.431

16. Medical Genetics So the results of the above data are: Greenland: p=0.835 + ½ (0.156)=0.913 and q=0.009 + ½ (0.156)=0.087 Iceland: p=0.312 + ½ (0.515)=0.569 and q=0.173 + ½ (0.515)=0.431 Clearly the allelic frequencies vary between these populations.

17. Medical Genetics 2. The Hardy-Weinberg Law The Hardy-Weinberg Law The unifying concept of population genetics Named after the two scientists who simultaneously discovered the law The law predicts how gene frequencies will be transmitted from generation to generation given a specific set of assumptions.

18. Medical Genetics If an infinitely large, random mating population is free from outside evolutionary forces (i.e. mutation, migration and natural selection), then the gene frequencies will not change over time, and the frequencies in the next generation will be: p2 for the AA genotype 2pq for the Aa genotype, and q2 for the aa genotype.

19. Medical Genetics Let's examine the assumptions and conclusions in more detail starting first with the assumptions.

20. Medical Genetics A.Infinitely large population 1.No such population actually exists. 2.The effect that is of concern is genetic drift (a change in gene frequency that is the result of chance deviation from expected genotypic frequencies) a problem in small populations.

21. Medical Genetics B. Random mating Random mating - matings in a population that occur in proportion to their allelic frequencies.

22. Medical Genetics For example, if the allelic frequencies in a population are: f(M) = 0.91 f(N) = 0.09 then the probability of MM individuals occurring is 0.91 x 0.91 =0.828. If a significant deviation occurred, then random mating did not happen in this population.

23. Medical Genetics Within a population, random mating can be occurring at some loci but not at others. Examples of random mating loci - blood type, RFLP patterns Examples of non-random mating loci - intelligence, physical stature

24. Medical Genetics C. No evolutionary forces affecting the population The principal forces are: 1.Mutation 2.Migration 3.Selection Some loci in a population may be affected by these forces, and others may not; those loci not affected by the forces can by analyzed as a Hardy-Weinberg population

25. Medical Genetics Mathematical Derivation of the Hardy-Weinberg Law If p equals the frequency of allele A in a population and q is the frequency of allele a in the same population, union of gametes would occur with the following genotypic frequencies:

26. Medical Genetics *The gamete and offspring genotypes are in parentheses. From the table, it is clear that the prediction regarding genotypic frequencies after one generation of random mating is correct. That is: AA = p2; Aa = 2pq; and aa = q2 Female Gametes * p(A)p(A) q(a)q(a) Male Gametes p(A)p(A) p 2 (AA) pq (Aa) q(a)q(a) q 2 (aa)

27. Medical Genetics Prediction regarding stability of gene frequencies The following is a mathematical proof of the second prediction. To determine the allelic frequency, they can be derived from the genotypic frequencies as shown above. p = f(AA) + ½f(Aa)(substitute from the table on previous page) p = p 2 + ½(2pq)(factor out p and divide) p = p(p + q) (p + q =1; therefore q =1 - p; make this substitution) p = p [p + (1 - p)](subtract and multiply) p = p

28. Medical Genetics Evolutionary Genetics The Hardy-Weinberg Law described a population that exists in genetic equilibrium where allelic frequencies do not change from generation to generation. For evolution of a population to occur, the gene frequencies of that population must undergo change. Several factors can act to change fitness or the ability to maintain allelic frequencies. –Viability - ability to survive –Fertility - ability to reproduce By altering the fitness of an individual, the mating distribution will change, and consequently the allelic frequencies will change and the population will evolve.

29. Medical Genetics 3. Factors that Affect Stability of Gene Frequencies A.Mutation 1.Classified as beneficial, harmful or neutral; 2.Can occur by point mutations ; or small insertions or deletions of the nucleotide sequence; 3.Harmful mutations are lost if they reduce fitness; 4.If fitness is improved by a mutation, then the frequency of that allele will increase from generation to generation; 5.The mutation could be a change in one allele to resemble one currently in the population, for example from a dominant to a recessive allele;

30. Medical Genetics 6 The mutation could generate an entirely new allele. –Most of these mutations though will be detrimental and lost. –If the environment changes, the new mutant allele may be favored and eventually become the dominant alelle in that population. –If the mutation is beneficial to the species as a whole, migration must occur for it to spread to other populations of the species. 7 Gene duplication favor mutational events. –The duplicated gene can undergo mutations to generate a new gene that has a similar, but a slightly modified function for the organism. –This type of evolution generates multigene families. (Examples: hemoglobin and muscle genes in humans, and seed storage and photosynthetic genes in plants)

31. Medical Genetics B.Migration 1.The Hardy-Weinberg Law assumes the population is closed. But for many populations this is not the case. 2. Migration will change gene frequencies by bringing in more copies of an allele already in the population or by bringing in a new allele that has arisen by mutation. 3. Because mutations do not occur in every population, migration will be required for that allele to spread throughout that species.

32. Medical Genetics 4. In a genetic context, migration requires the introduction of new alleles into the population. This will only occur after the migrant has successfully mated with an individual in the population. The term that is used to described this introduction of new alleles is gene flow. 5. The two effects of migration are to: (1) increase variability within a population (2) prevent a population of that species from diverging to the extent that it becomes a new species.

33. Medical Genetics C. Selection 1.Mutation causes new functions for the individual. 2.These new forms may or may not add to the fitness of the individual. 3.If the fitness of the individual leads to a reproductive advantage, then the alleles present in that individual will be more prevalent in the next generation of the population. 4.A population undergoes selection when certain alleles are preferentially found in a new generation because of the increased fitness of the parent. 5.The alleles in the individual with increased fitness will increase in frequency in the population. 6.In a Darwinian context, mutation, migration and selection lead to changes in gene frequencies, and the population evolves by natural selection.