* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Lec3
Genetic code wikipedia , lookup
Genetic studies on Bulgarians wikipedia , lookup
Dual inheritance theory wikipedia , lookup
Designer baby wikipedia , lookup
Medical genetics wikipedia , lookup
History of genetic engineering wikipedia , lookup
Pharmacogenomics wikipedia , lookup
Genetic engineering wikipedia , lookup
Public health genomics wikipedia , lookup
Genetic testing wikipedia , lookup
Koinophilia wikipedia , lookup
Inbreeding avoidance wikipedia , lookup
Polymorphism (biology) wikipedia , lookup
Behavioural genetics wikipedia , lookup
Dominance (genetics) wikipedia , lookup
Genetics and archaeogenetics of South Asia wikipedia , lookup
Genome (book) wikipedia , lookup
Quantitative trait locus wikipedia , lookup
Heritability of IQ wikipedia , lookup
Genetic drift wikipedia , lookup
Hardy–Weinberg principle wikipedia , lookup
Population genetics wikipedia , lookup
Variation Lecture 4-5 Sources of Phenotypic Variation Phenotype Characteristic in an individual organism or group of individuals that are alike Level of gene expression is a phenotype Sources of Phenotypic Variation Phenotypic variation is the result of: • Genetic differences among individuals Ex: Snow goose • Environmental variation on development Ex: Ptarmigan Because evolution consists of genetic changes in populations over time, evolutionary biologists are most interested in those variations that have genetic basis Sources of Phenotypic Variation Genotype Genetic constitution at one or more loci of an individual organism or a group of organisms that are alike The number of alleles or loci that contribute to genetic variation in a phenotypic trait differs from case to case Sources of Phenotypic Variation Variation comes in many forms: • Two or three alleles at the same locus Ex: Snow goose and swallowtail butterfly (color patterns of wings) • Multiples alleles at different loci Ex: Land snail (color patterns of shell bands) • Multiple loci contributing to continuous variation Ex: Human (color of hair and skin) Sources of Phenotypic Variation Variation in a phenotypic character can have several sources other than those encoded in DNA sequences The environment directly affects the development or expression of many features: Permanent effects: environmental sex determination Temporary effects: enzyme induction Environmental Variance: Environmentally induced variation among individuals Developmental Noise: phenotypic variation observed even when genetic and environmental variation are eliminated is caused by random events at the molecular level: fluctuating asymmetry Phenotype= Genes + Environment + Noise Sources of Phenotypic Variation Maternal effects: Effects of a mother on her offspring that are due not to the genes they inherit from her but rather to non-genetic influences Amount of yolk in eggs, amount of maternal care Epigenetic inheritance: Some phenotypic differences that are not based on DNA sequence differences are sometimes transmitted from parents to offspring Genomic imprinting Because evolution depends on the genetic component of variation, it is often critically important to determine whether variation in a characteristic is genetic, environmental or both Lecture Ideas • Genetic variation is a necessary condition for evolution • Variability is achieved through the process of mutation: • Mutation rate (per individual gene per generation) is low but provides abundant genetic variation within a population • Recombination also generates variability • Mutation is NOT the cause of evolution • Phenotypic variation results from genotypic and environmental variation Fundamental Principles of Genetic Variation in Pops We are interested in genetic variation and the factors that cause evolution within species At any given gene locus a population may contain 2 or more alleles that have arisen over time by mutation. WILD TYPE refers to the most common allele ALLELE FREQUENCY Proportion of a population that has a certain allele In sexually reproducing populations, the alleles, carried in eggs and sperm, become combined into homozygous and heterozygous genotypes GENOTYPE FREQUENCY Proportion of a population that has a certain genotype Fundamental Principles of Genetic Variation in Pops Any alteration of the genotype frequencies in one generation will alter the frequencies of the allele carried by the population’s gametes when reproduction occurs, so the genotype frequencies of the following generation will be altered in turn. Such alteration, from generation to generation, is the central process of evolutionary change However the genotype and allele frequencies do not change on their own; something has to change them. The factors that can cause the frequencies to change are the causes of evolution Fundamental Principles of Genetic Variation in Pops Frequencies of Alleles and Genotypes Consider alleles A1 and A2 If there are 400 A1 A1, 400 A1A2, and 200 A2A2 individuals What are the genotype and allele frequencies in this population? Fundamental Principles of Genetic Variation in Pops Frequencies of Alleles and Genotypes Consider N, alleles A1 and A2, genotypes A1 A1, A1A2, A2A1, and A2A2 The parental genotype and allele frequencies are Genotype 1000 N=1000 400 400 200 A1 A1 A1A2 A2A2 Allele D H R 0.4 0.4 0.2 A1 A2 p=D+H/2 q=R+H/2 0.6 0.4 Fundamental Principles of Genetic Variation in Pops Frequencies of Alleles and Genotypes Assume genotype equally represented in females and males and random mating If the previous is the parental population What is the frequency of each genotype among the offspring generation ? Fundamental Principles of Genetic Variation in Pops Frequencies of Alleles and Genotypes Assume genotype equally represented in females and males and random mating Mating Prob Mating Fem x Mal Offspring Genotype A1 A1 A1 A2 A2 A2 A1 A1 x A1 A1 D2 1 0 0 A1 A1 x A1 A2 2DH ½ ½ 0 A1 A1 x A2 A2 2DR 0 1 0 A1 A2 x A1 A2 H2 ¼ ½ ¼ A1 A2 x A2 A2 2HR 0 ½ ½ A2 A2 x A2 A2 R2 0 0 1 The frequency of each genotype among the offspring is: A1A1 A1A2 A2A2 D2 + ½2DH + ¼H2 = (D+H/2)2 = p2 ½2DH + 2DR + ½H2 + ½2HR = 2[(D+H/2)+(H/2+R)] = 2pq ¼H2 + ½2HR + R2 = (R+H/2)2 = q2 Fundamental Principles of Genetic Variation in Pops Frequencies of Alleles and Genotypes If genotypes mate at random, gametes, and therefore genes, unite at random to form zygotes Sperm A1 (p) A2 (q) Eggs A1 (p) A1A1 (p2) A1A2 (pq) A2 (q) A2A1 (pq) A1A1 (q2) What is the frequency of each allele among the offspring generation ? Fundamental Principles of Genetic Variation in Pops Frequencies of Alleles and Genotypes If genotypes mate at random, gametes, and therefore genes, unite at random to form zygotes Sperm A1 (p) A2 (q) Eggs A1 (p) A1A1 (p2) A1A2 (pq) A2 (q) A2A1 (pq) A2A2 (q2) The frequency of each allele among the offspring is: A1 p2 + ½2pq = p A2 ½2pq + q2 = q The allele frequencies do not change from one generation to the next Fundamental Principles of Genetic Variation in Pops Frequencies of Alleles and Genotypes The offspring genotype and allele frequencies are If there are 400 A1 A1, 400 A1A2, and 200 A2A2 individuals What are the genotype and allele frequencies in the offspring population? Fundamental Principles of Genetic Variation in Pops Frequencies of Alleles and Genotypes The offspring genotype and allele frequencies are Genotype A1 A1 A1A2 A2A2 Allele p2 2pq q2 0.36 0.48 0.16 A1 A2 p q 0.6 0.4 The allele frequencies have not changed from one generation to the next , although the alleles have become distributed among the three genotypes Fundamental Principles of Genetic Variation in Pops Frequencies of Alleles and Genotypes HARDY-WEINBERG PRINCIPLE • Whatever the initial genotype frequencies for two alleles may be, after one generation of random mating, the genotype frequencies will be p2:2pq:q2 • Both these genotype frequencies and the allele frequencies will remain constant in succeeding generations … unless some factor change them When the genotypes at a locus have the frequencies predicted by the HardyWeinberg principle the locus is said to be in HARDY-WEINBERG EQUILIBRIUM Example: Human MN Locus Two alleles M, N. Sample 320. MM 187, MN 114, NN 19 Frequency of each genotype? Allele frequencies? Expected vs observed number of individuals? Fundamental Principles of Genetic Variation in Pops The Significance of the Hardy-Weinberg Principle The Hardy-Weinberg principle is the foundation on which almost all of the theory of population genetics of sexually reproducing organisms rests The study of genetic evolution consists of asking what happens when one or more of the assumptions of the Hardy-Weinberg principle are relaxed The most important assumptions are: 1. 2. 3. 4. 5. Infinite population (random genetic drift) Random mating No migration No mutation No natural selection Thus the major factors that cause evolutionary change within populations are chance, nonrandom mating, gene flow, mutation and selection. Other assumptions: a. Autosomal loci (sex-linked loci) b. Mendelian segregation (segregation distortion) If these assumptions hold true for a particular locus, that locus will display Hardy-Weinberg genotype frequencies. But if we observe that a locus fits the Hardy-Weinberg frequency distributions we cannot conclude that the assumptions hold true! Fundamental Principles of Genetic Variation in Pops Frequency of Alleles, Genotypes and Phenotypes At Hardy-Weinberg equilibrium when is the frequency of heterozygotes greatest? Fundamental Principles of Genetic Variation in Pops Frequency of Alleles, Genotypes and Phenotypes At Hardy-Weinberg equilibrium, the frequency of heterozygotes is greatest when alleles have equal frequency When an allele is rare almost all its carriers are heterozygous: A rare recessive allele may not be detected: populations can carry concealed genetic variation Fundamental Principles of Genetic Variation in Pops Inbreeding INBREEDING is a form on non-random mating that occurs when the gene copies in uniting gametes are more likely to be identical by descent than if they joined at random IDENTICAL BY DESCENT Gene copies that have descended from a common ancestor What is the probability that the two gene copies the offspring of a brother and a sister are identical by descent? Fundamental Principles of Genetic Variation in Pops Inbreeding INBREEDING is a form on non-random mating that occurs when the gene copies in uniting gametes are more likely to be identical by descent than if they joined at random IDENTICAL BY DESCENT Gene copies that have descended from a common ancestor A1*A2 A1A2 A1*A1 A1*A2 A2A1 A1*A1* A1A1* A1*A2 A1A2 homozygote heterozygote autozygous allozygous A2A2 AUTOZYGOUS Individuals that carry two gene copies identical by descent. They are necessarily homozygous ALLOZYGOUS Individuals that carry two gene copies that are not identical by descent. They might be homozygous or heterozygous Fundamental Principles of Genetic Variation in Pops Inbreeding Fundamental Principles of Genetic Variation in Pops Inbreeding He was born physically and mentally disabled, and disfigured. Possibly through affliction with mandibular prognathism, he was unable to chew. His tongue was so large that his speech could barely be understood, and he frequently drooled. It has been suggested that he suffered from the endocrine disease acromegaly, or his inbred lineage may have led to a combination of rare genetic disorders such as combined pituitary hormone deficiency and distal renal tubular acidosis. Consequently, Charles II is known in Spanish history as El Hechizado ("The Hexed") from the popular belief that his physical and mental disabilities were caused by "sorcery." The king went so far as to be exorcised Fundamental Principles of Genetic Variation in Pops Inbreeding Fundamental Principles of Genetic Variation in Pops Inbreeding The inbreeding coefficient (F) is the probability that an individual taken at random from the population will be autozygous : • Not inbred F=0 • Inbred F=1 In a population in which there might be inbreeding what are the genotype frequencies? Fundamental Principles of Genetic Variation in Pops Inbreeding The inbreeding coefficient (F) is the probability that an individual taken at random from the population will be autozygous : • Not inbred F=0 • Inbred F=1 Taking into account the allozygous and autozygous fractions of the population, the genotype frequencies are Allozygous Autozygous Genotype Frequency A 1 A1 (1-F) p2 Fp p2 + Fpq = D A 1 A2 (1-F) 2pq A 2 A2 (1-F) q2 2pq (1-F) = H Fq q2 + Fpq = R The consequence of inbreeding is that the frequency of homozygotes is higher, and the frequency of heterozygotes is lower than in a HardyWeinberg equilibrium Fundamental Principles of Genetic Variation in Pops Inbreeding We can estimate the inbreeding coefficient by two measurable quantities : • The observed frequency of heterozygotes H • The expected frequency of heterozygotes H0 If p=0.4, q=0.6 and the observed frequency of heterozygotes is 0.24 What is the inbreeding coefficient in this population? Fundamental Principles of Genetic Variation in Pops Inbreeding We can estimate the inbreeding coefficient by two measurable quantities : • The observed frequency of heterozygotes H • The expected frequency of heterozygotes 2pq Example: p=0.4, q=0.6, H=0.24, F? Fundamental Principles of Genetic Variation in Pops Inbreeding If consanguineous mating is a consistent feature of a population, F will increase over generations at a rate that depends on how closely related the average pair of mates is The most extensive form of inbreeding, self-fertilization or selfing, occurs in many species of plants and a few animals Genotype frequencies observed at two loci of wild Oat (Avena fatua) Genetic Variation in Natural Populations Polymorphism GENETIC POLYMORPHISM is the presence in a population of two or more variants (alleles or haplotypes) MONOMORPHIC character is a character that is not polymorphic Genetic Variation in Natural Populations Genetic Variation in Viability RECESSIVE LETHAL ALLELE Allele that causes death before the carrier reaches the adult stage Frequency distribution of relative viabilities of chromosomes extracted from a wild population of D. pseudoobscura Greater viability of heterozygotes Presence of recessive deleterious alleles The average person carries heterozygously the equivalent of 3-5 recessive lethal alleles acting between late fetal and early adult stages Disease and Variation Genetic Variation in Natural Populations Inbreeding Depression Because populations of humans and other diploid species harbor recessive alleles that have deleterious effects, and because inbreeding increases the proportion of homozygotes, populations in which many matings are consanguineous often manifest a decline in components of fitness, such as survival and fecundity. Such a decline is called INBREEDING DEPRESSION Marriages 19031907 in Italian populations Genetic Variation in Natural Populations Inbreeding Depression Small Swedish population of adders. Population decline due to inbreeding followed by increase due to introduction of new individuals Genetic Variation in Natural Populations Variation in Proteins Evolution would be very slow if populations were genetically uniform, and if only occasional mutations arose and replaced pre-existing genotypes. In order to know what the potential is for rapid evolutionary change, it would be useful to know how much genetic variation natural population contain Lewontin and Hubby How much variation? Genetic Variation in Natural Populations Variation in Proteins Drosophila Humans H=0.12 H=0.07 Humans between 1400 and 1750 (from estimates of 20 to 25 thousand genes) polymorphic loci Considering 2 alleles per locus this yields 31400 to 31750 different genotypes Populations are far more genetically diverse than almost anyone imagined What are the factors responsible for such variation? Genetic Variation in Natural Populations Multiple Loci and the Effects of Linkage Each gene is LINKED to certain other genes, meaning that they are physically associated on the same chromosome This linkage is important because under some circumstances changes in allele frequencies at one locus cause correlated changes at other loci with which that locus is linked LINKAGE DISEQUILIBRIUM is the nonrandom association of alleles at two or more loci, not necessarily on the same chromosome Genetic Variation in Natural Populations Multiple Loci and the Effects of Linkage Recombination during meiosis reduces the level of linkage disequilibrium and brings the loci toward linkage equilibrium A1B1/A1B1 pA2pB2 Whether loci are in linkage equilibrium or disequilibrium, the genotype frequencies at each locus conform to H-W frequencies Genetic Variation in Natural Populations Multiple Loci and the Effects of Linkage Mating Prob Egg x Spe Offspring Genotype A1 B 1 A1 B 2 A2B 1 A2 A2 A1 B 1 x A1 B 1 x1 2 1 0 0 0 A1 B 1 x A1 B 2 2x1x2 ½ ½ 0 0 A1 B 1 x A2 B 1 2x1x3 ½ 0 ½ 0 ½(1r) ½r ½r ½(1-r) A1B1 x A2B2 2x1x4 A1 B 2 x A1 B 2 x2 2 0 1 0 0 A1 B 2 x A2 B 1 2x2x3 ½r ½(1r) ½(1r) ½r AB x 2x x 0 ½ 0 ½ 2 0 0 1 0 1 2 2 4 x1’=x -r(x x -x x3) 1 1 4 2 AB 2 2 A B xA B x Genetic Variation in Natural Populations Multiple Loci and the Effects of Linkage Linkage disequilibrium: Interpretation x1-pA1pB1=D Linkage disequilibrium: Decay D’=x1’x4’-x2’x3’ x1’=x1-rD x2’=x2+rD x3’=x3+rD x4’=x4-rD D’=(1-r)D Dt=(1-r)tD0 Genetic Variation in Natural Populations Multiple Loci and the Effects of Linkage Linkage disequilibrium is common in: • Asexual populations • Very close molecular markers Linkage disequilibrium mapping In panmictic sexually reproducing populations is rare Length of stamens and style in the European primrose Genetic Variation in Natural Populations Variation in Quantitative Traits SOURCES OF VARIATION Discrete genetic polymorphisms in phenotypic traits are much less common than slight differences among individuals Quantitative/Continuous/Metric variation often fits a normal distribution The genetic component of such variation is often polygenic: due to variation at several or many loci each of which contributes to the variation in phenotype Genetic Variation in Natural Populations Variation in Quantitative Traits Quantitative characters often vary both because of genes and because of nongenetic environmental factors The relative amounts of genetic and environmental variation can differ with different circumstances even in the same population. Phenotype (P)= Genotype (G) + Environment (E) Genetic Variation in Natural Populations Variation in Quantitative Traits ESTIMATING COMPONENTS OF VARIATION The description and analysis of quantitative variation are based on statistical measures because the loci that contribute to quantitative variation generally cannot be singled out for study VARIANCE Quantifies the spread of individual values around the mean value 1 2 V ni X i x n 1 Xi ni Characteristic of an individual Number of individuals Standard Deviation s V Genetic Variation in Natural Populations Variation in Quantitative Traits Var[P]= Var[G]+Var[E]+2 Cov[G,E] Assuming Cov[G,E]=0 Dividing by Var[P] 1=Var[G]/Var[P]+Var[E]/Var[P]+2 Cov[G,E]/Var[P] Genetic Variation in Natural Populations Variation in Quantitative Traits In simple cases the variance in a phenotypic character VP is the sum of genetic variance VG and environmental variance VE VP = VG + VE VG Amount of variation among the averages of the different genotypes VE Average amount of variation among individuals with the same genotype HERITABILITY Proportion of phenotypic variance that is genetic variance VG h VG VE 2 Genetic Variation in Natural Populations Variation in Quantitative Traits One way of estimating h2 is as the regression coefficient of offspring mean on the mean of the two parents Genetic Variation in Natural Populations Phenotypic variation has a genetic component and an environmental component In an ideal population where natural selection is not acting Population is in Hardy Weinberg equilibrium after one generation Reductions in variation: Inbreeding: increases homozygosity Reduced recombination: generates linkage disequilibrium Heritability explains the fraction of the variation that can be explained by genetic factors