Genetic Variation within Populations Population Genetics Darwin s Observations Genetic Variation Underlying phenotypic variation is genetic variation. The potential for genetic variation in individuals of a population is unlimited Unlimited genetic variation, in the form of new alleles and new combinations of alleles, increases the chance that a population will survive future environmental changes. How do new alleles arise in a population? 1
Natural Selection & Evolution Natural selection is differential survival and reproduction. Populations (not individuals) evolve. Populations are defined as a group of interbreeding individuals of a single species that share a common geographic area. Evolution is measured as the change in relative proportions of heritable variation in a population over a succession of generations. Population Genetics 1. Integrates Darwin s Theory of Natural Selection with Mendelian Genetics 2. Genes/alleles and their relative abundance (frequency) within and among populations. 3. How/why do allele frequencies change? 4. Microevolution 5. Assessing genetic variation using molecular techniques. The life cycle of an imaginary population of mice 2
Hardy-Weinberg Principle If: 1) Mating is random across the entire population. 2) All genotypes (individuals) have equal success at surviving or reproducing (no selection). 3) There is no migration/emigration of individuals (gene flow). 4) There is no mutation. 5) Population is large enough so that the allele frequencies do not change from generation to generation just by chance alone (random genetic drift). Then: allele frequencies will not change from one generation to the next and the population is said to be in Hardy-Weinberg equillibrium A gene pool with allele frequencies of 0.6 for allele A and 0.4 for allele a. Allele and genotype frequencies throughout the life cycle in a numerical simulation 3
When the adults in our model mouse population make gametes, they produce a gene pool in which the allele frequencies are identical to the ones we started with a generation ago Hardy-Weinberg Calculations If frequency of the dominant allele (A) in the population is p, and the frequency of the recessive allele (a) is q, then p + q = 1 Frequency of heterozygotes (Aa), dominant homozygotes (AA) and recessive homozygotes (aa) is: p 2 + 2pq + q 2 = 1 AA Aa aa 4
Hardy -Weinberg If p+q=1.0 (allele frequencies) Then p 2 + 2pq + q 2 = 1.0 (genotype frequencies) If you know the allele frequencies, you can predict the genotype frequencies: Selection can cause allele frequencies to change across generations (1) Persistent selection can produce substantial changes in allele frequencies over time (2)Each curve shows the change in allele frequency over time under a particular selection intensity. 5
Frequencies of the Adh F allele in four populations of fruit flies over 50 generations Red + orange dots = flies reared on food spiked with ethanol Macrophage 6
What accounts for this variation? Random? Past epidemics (plague, smallpox)? What will happen to this variation in the future? Will Δ32 allele increase in frequency? Selection will increase the frequency of Δ32 allele Selection is relatively weak The favored allele is recessive and the favored genotype is very rare The change in allele frequency (response to selection) will be relatively slow Industrial Melanism Classic example of natural selection Kettlewell (1959) conducted experiments to measure the survival of different genotypes Calculated change in frequency of dark and light individuals 7
Battling malaria: natural selection is fast! DDT developed in 1942, used in India in late 1940 s 10 years later, nearly useless due to resistant mosquito strains 95% effective initially but 16 months later only 20% effective Mutation is a weak mechanism of evolution 8
Mutation causes variation e.g. Sickle cell anemia Hemoglobin gene DNA sequence containing a specific mutation in the nucleotide sequence causes a hydrophilic amino acid, glutamine, to be substituted by a hydrophobic amino acid, valine. Profound effects on the folding pattern of the hemoglobin, altering its functionality. Normal Homozygotes Homozygous individuals, AA Healthy In the A allele, the 6th codon is CTC = glutamine Sickle-cell Homozygotes In the a allele, the 6th codon has mutated to CAC = valine causes distortion in shape of red blood corpuscles 80% of homozygous (aa) individuals die before reproducing why still around? 9
Effect of Migration and Small Population size Gene Flow - the gradual exchange of genes/alleles between two populations brought about by the dispersal of gametes or the migration of individuals. Genetic Drift - random variation in allele frequency from generation to generation. Most often observed in small populations. Migration can alter allele and genotype frequencies 10
Population size and drift Small populations vary more in allele frequencies due to sampling effects from one generation to the next variance in frequency of an allele with frequency depends on population size, N Smaller N => more variance, more drift Genetic Drift Random sampling/variation in allele frequency from generation to generation Occurs when the number of reproducing individuals in a population is too small to ensure that all the alleles in the gene pool will be passed to the next generation in their existing frequencies Chance events (Genetic Drift) can alter allele and genotype frequencies 11
Flip a coin Observe 10 sets of 20 coin tosses and 10 sets of 4000 coin tosses On average all sets would have 50% heads and tails But it is more likely to flip 12 heads : 8 tails in the small population than 2400 heads : 1600 tails in the large population Bottlenecks Populations may go through a bottleneck in size Out of many individuals, only a few contribute to the next generation A special type of bottleneck is the reduction in population size associated with colonization - founder effect Genetic Bottleneck 12
Small Populations & The Founder Effect The establishment of a new population by a few original founders (in an extreme case, by a single fertilized female) that carry only a small fraction of the total genetic variation of the parental population. (Mayr, 1963) The Amish Small group of Germans began the Amish community in Pennsylvania 1 possessed an allele for polydactylism (more than five fingers or toes on a limb). After 200 years of reproductive isolation the number of cases among the Amish population exceeds the number of cases occurring in the entire world s population Inbreeding alters genotype frequencies 13
Inbreeding Self-fertilization Sewell Wright: Inbreeding Coefficient (F) F quantifies the probability that the two alleles of a given gene in an individual are identical because they are descended from the same single copy of the allele in an ancestor. If F =1 all individuals in the population are homozygous, and both alleles in every individual are derived from the same ancestral copy. If F=0 no individual has two alleles derived from a common ancestral copy Inbreeding Sewell Wright: Inbreeding Coefficient (F) Based on the inverse relationship between inbreeding and the frequency of heterozygotes As inbreeding increases, heterozygosity decreases F= H e - H o /H e H e = expected heterozygosity H o = observed heterozygosity In a completely randon mating population the expected and Observed levels of heterozygosity will be equal so F=0 14
Inbreeding Depression Inbred populations often have a lowered mean fitness. Inbreeding depression is a measure of the loss of fitness caused by inbreeding Inbreeding results in higher levels of homozygosity Some recessive alleles are deleterious 15
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