分子课件顾正龙_第1页
分子课件顾正龙_第2页
分子课件顾正龙_第3页
分子课件顾正龙_第4页
分子课件顾正龙_第5页
已阅读5页,还剩167页未读 继续免费阅读

下载本文档

版权说明:本文档由用户提供并上传,收益归属内容提供方,若内容存在侵权,请进行举报或认领

文档简介

1、Evolutionary Forcesemail: Microevolution vs. Macroevolution Microevolution: small-scale changes in allele frequencies from generation to generation (population genetics) Macroevolution biological evolution over many generations and on the origin of higher taxonomic categories (at or a

2、bove the species)Evolution deals with the change in gene frequency of a population from generation to generation FemalesA (p)a (q)MalesA (p)AA (p)Aa (pq)a (q)Aa (pq)aa (q)HardyWeinberg equilibriumKnow how to calculate the expected frequencies for multiple alleles Females A1 (p)A2 (q)A3(r)MalesA1 (p)

3、A1A1 (p)A1A2 (pq)A1A3 (pr)A2 (q)A1A2 (pq)A2A2 (q)A2A3 (qr) A3 (r)A1A3 (pr)A2A3 (qr)A3A3 (r)p+q+r =1Three alleles for one locus: A1 (p), A2 (q), A3 (r)Three-allele HardyWeinberg equilibriumGenotypeFrequencyA1A1pA2A2qA3A3rA1A22pqA2A32qrA1A32prp + q + r + 2pq + 2pr + 2qr= (p+q+r) = 1 Three-allele Hardy

4、Weinberg equilibriumAssumption for HardyWeinberg Equilibrium:1.No selection 2.No migration (gene flow) 3.Infinite population size4.No mutation 5.Forces to change the genetic frequency are the Violation of assumptionPopulation genetics is the study of the allele frequency distribution and change unde

5、r the influence of the four evolutionary forces: mutation, natural selection, gene flow, and genetic drift Deleterious, Neutral & Adaptive mutationsMutation is the ultimate source for genetic variation and thus evolutionMutationMutation Selection filter, positive negativeEvolutionRecombination c

6、an reshuffle mutationsAssortment of MutationsEpistasis: the phenomenon where the effects of one mutation are modified by one or several other mutations Fitness is an individuals ability to propagate its genes Selection coefficient measures the intensity of natural selection acting on the genotypes i

7、n the population (fitness of the phenotype). Natural selection Positive selection (directional selection): favorable traits that are heritable become more common in successive generations Negative selection (stabilizing or purifying selection): unfavorable traits that are heritable become less commo

8、n (disease)Natural selectionNatural Selection on Beach Mouse Color PatternSCIENCE 313, 2006A Single Amino Acid Mutation Contributes to Adaptive Beach Mouse Color PatternNatural populations of beach mice exhibit a characteristic color pattern, relative to their mainland conspecifics, driven by natura

9、l selection for crypsis. The authors identified a derived, charge-changing amino acid mutation in the melanocortin-1 receptor (Mc1r) in beach mice, which decreases receptor function.Amylase Gene Copy Number Variation and Rice EatingNature Genetics, 2007Balancing SelectionSelection for the heterozygo

10、te, i.e., heterozygote genotype might be more fit to the specific environment than other two homozygotesSickle Cell DiseaseSickle Cell DiseaseGlutamineValineHbAHbSHemoglobine peptideCTCCAC HbA/HbA: 100% normal hemoglobine HbA/HbS: 60% normal and 40% mutant henoglobine HbS/HbS: 100% mutant hemoglobin

11、e (almost lethal)Why in certain populations the HbS allele frequency can be as high as 40%?Heterozygote advantage and balancing selectionSelection from malaria by Plasmodium ParasiteGene flow50 feet15 kmExchange of genetic information between populationsThe frequencies of alleles A and a are 0.3 &am

12、p; 0.7 for the mainland, 0.6 & 0.4 for the island, respectively. 100 individual migrated from mainland to island. What are the frequencies of the AA, Aa and aa individuals in the island after one generation of random mating (assuming no drift and no selection)?1001000MainlandIsland100,000Island

13、model for population structureBreeding between Neanderthals and Modern HumanBreeding between Neanderthals and Modern HumanThe Shaping of Modern Human Immune Systems by Multiregional Admixture with Archaic Humans.Science. 2011 Aug 25Whole-genome comparisons identified introgression from archaic to mo

14、dern humans. Our analysis of highly polymorphic HLA class I, vital immune system components subject to strong balancing selection, shows how modern humans acquired the HLA-B*73 allele in west Asia through admixture with archaic humans called Denisovans, a likely sister group to the Neandertals. The

15、Shaping of Modern Human Immune Systems by Multiregional Admixture with Archaic Humans.Science. 2011 Aug 25Virtual genotyping of Denisovan and Neandertal genomes identified archaic HLA haplotypes carrying functionally distinctive alleles that have introgressed into modern Eurasian and Oceanian popula

16、tions. These alleles, of which several encode unique or strong ligands for natural killer cell receptors, now represent more than half the HLA alleles of modern Eurasians and also appear to have been later introduced into Africans. Thus, adaptive introgression of archaic alleles has significantly sh

17、aped modern human immune systems.What Part of Me is Neanderthal?Finite Population Size: Genetic DriftToss coin 1000 times, what are the frequency of the head?Genetic drift addresses the influence random chance has on the survival of alleles, due to the statistical effectHow about toss only 10 times?

18、Which experiment is easier to get 40% heads?N = 100N = 10Founder effect (Bottleneck)The effect of establishing a new population by a small number of individuals, carrying only a small fraction of the original populations genetic variation Can cause high frequency even for deleterious alleles 10,0001

19、00,000Founder effect 1000 10A:50%, a:50%Mutiny on the Bounty (1789) Pitcairn Island (1790) 9 mutineers (British) 6 Tahiti men 12 Tahiti women British ship HMS Bounty, Tahiti Fletcher Christian A high rate of retinoblastoma. Human evolutionOut of Africa vs. Multiple originReplace local population Fou

20、nder effectMix with local populationGene flow1. To know how to calculate genotype frequency based on the Hardy-Weinberg equilibrium, more than two alleles, island model, assumption 2. Evolutionary forces: Three types of natural selections, island model for gene flow (in combination with HWE). What i

21、s genetic drift? Founder effect?3. Understand Sickle Cell DiseasesNeutral Theory of EvolutionOutline Modern Synthesis Neutral Theory A. Patterns in DNA sequence B. Patterns in Population Diversity C. Nearly Neutral ModelModern Synthesis The modern evolutionary synthesis is a union of ideas from seve

22、ral biological specialties which provides a widely accepted account of evolution. It is also called new synthesis, the modern synthesis, the evolutionary synthesis, millennium synthesis and the neo-darwinian synthesisModern SynthesisCharles DarwinGregor MendelR.A. FisherJ.B.S. HaldaneSewall Wright G

23、enetics Evolution is gradual Population thinking Selection is overwhelmingly the main mechanism of changeThe Modern SynthesisT.G. DobzhanskyErnst MayrEarly empirical observationsProtein electrophoresis was used to reveal surprising amounts of genetic variability within populations. Harris studied 10

24、 loci in human populations, found three of them to be polymorphic, and identified one locus with three alleles. Hubby and Lewontin studied 18 loci in Drosophila pseudoobscura, found seven to be polymorphic, and five that had three or more allelesIt was similarly difficult to imagine that natural sel

25、ection could maintain so much polymorphism within populations. The “cost of selection as Haldane called it, would simply be too highFor any given protein the rate of molecular evolution is approximately constant in all evolutionary lineages. A key theory for the molecular phylogenyMolecular clock th

26、eory (Zuckerkandl & Pauling, 1965): Neutrality: all the genotypes at a locus have the same fitness (s), the condition is called selective neutrality Most evolutionary change is the result of genetic drift acting on neutral alleles Neutral Theory of EvolutionMotoo Kimura (木村木村 資生資生)Motoo Kimura M

27、asatoshi Nei Wen-Hsiung LiTomoko Ohta The neutral theory is easily misinterpreted. It does NOT suggest: That organisms are not adapted to their environmentsThat all morphological variation is neutral That ALL genetic variation is neutral That natural selection is unimportant in shaping genomes Neutr

28、alist and selectionist models of molecular evolutionNeutralist theory is not anti-Darwinist, but claims that fixation through selection occurs at low frequencyPatterns in DNA sequence: PseudogenePseudogenes are dysfunctional relatives of known genes that have lost their protein-coding ability or are

29、 no longer expressed in any cellsProcessed (or retrotransposed) pseudogenesNon-processed (or duplicated) pseudogenesDisabled genesIf a gene is a true pseudogene, its evolutionary rate reflects neutral rates. MutationSelection filter: positive or negativeEvolutionExonExonIntrondS: synonymous differen

30、cedN: non-synonymous differenceSynonymous & non-synonymous revisitPatterns in DNA sequence: Synonymous vs. Non-Synonymous ExonExonIntronMutationSelection filter: positive or negativeEvolutionFunction at the Synonymous SitesCodon Usage BiasPreferred CodonPreferred CodonSelection is stronger for h

31、ighly expressed genesCodon bias assures efficient translation and high accuracySelection is very strong to keep the codon usage bias in microorganisms such as bacteria and yeastCodon Usage BiasPatterns in DNA sequence: Variation Among Loci vs. functional importanceMutationSelection filter: positive

32、or negativeEvolutionPatterns in Population DiversityWhy ?African populations have higher genetic diversityHeterozygosity: the chance that two genes at a locus, drawn at random from the population, are different. What is heterozygosity?Population Variation and HeterozygosityA population will be more

33、genetically variable for neutral alleles when population size is bigger and the mutation rate is larger. African populations have higher genetic diversityNumber of heterozygous genotypes per individual at synonymous (S) or non-synonymous (NS) SNPs. Lohmueller et al, Nature 2008African populations ha

34、ve bigger Effective population size Effective population size (Ne): the number of breeding individuals in an idealized population that would show the same amount of dispersion of allele frequencies under random genetic drift. Breeding structure of the population, like sex ratio, population fluctuati

35、on, inbreeding etc., will affect the Ne values. Nearly Neutral TheoryThe nearly neutral theory of molecular evolution is a modification of the neutral theory of molecular evolution that accounts for slightly advantageous or deleterious mutations at the molecular levelTomoko Ohta (太田太田 朋子朋子)Slightly

36、deleterious mutation: |s|1/(2*Ne)Near-Neutral theorySelection coefficient (s)1/(2*Ne)DeleteriousNeutralMutationSelection filter: positive or negativeEvolutionAdvantageous1/(2*Ne1)Slightly deleterious mutation: |s| Ne2 DeleteriousNeutralDeleterious mutations have higher chance to be fixed in smaller

37、populationsSelection coefficient (s)AdvantageousProportionally more deleterious genetic variation in European than in African populations Lohmueller et al, Nature 2008(PO): possibly damaging (PR) probably damagingPatterns in Population DiversityContribution of neutral theory for evolutionNatural Sel

38、ection Natural Selection and Variation Detecting Natural SelectionIn nature, there is a struggle for existenceThe condition of “excess” fecundity, where female produce more offspring than that can survive, is universal in nature.Natural SelectionThe unequal survival and reproduction of organisms due

39、 to environmental forces, resulting in the preservation of favorable adaptations.Natural selection operates if the following conditions are met:A.Reproduction. Entities must reproduce to form a new generationB.Heredity. The offspring must tend to resemble their parentsC.Variation in individual chara

40、cter among the members of the populationD.Variation in the fitness of organisms according to the state they have for a heritable characterA.Morphological levelB.Cellular level (Human chromosomal structure variation)C.Biochemical level (e.g. protein function)D.DNA level (e.g. SNPs between individuals

41、)Widespread Variation in natural population Real butterfly wing!There are millions of single nucleotide polymorphism (SNP) sites between two sets of chromosomes in each individual!Human copy number variation region(1,447 CNVR in 270 individuals)Redon et al, Nature, 2006Natural SelectionIt is a two s

42、tep process: 1. The production of variation in a population2. Non-random aspects of survival and reproductionTwo step process: Step One: The Production of Variation. (Chance)MutationsMeiosis:recombination due to crossing-over in 1st divisionrandom movement of chromosomes in 2nd divisionRandom mate s

43、election & fertilizationStep Two: Non-random aspects of survival and reproductionSuperior success of certain phenotypesNonrandom mate choiceNatural selection includes both positive and negative selectionIndividuals that have traits that are best adapted for the current environment are the ones t

44、hat survive to breed and pass on their genes to the next generation. Organisms not possessing the beneficial traits either die or dont have as many offspring.NOBODY!Natural Selection is survival of the fittest. Natural selection is a process of elimination. There is no agent involved in natural sele

45、ction. Antagonistic PleiotropyFitness tradeoff, genes important in one condition could be deleterious in the other condition(s).Adaptation should be put in contextAdaptation could be associated with diseases Natural Selection and Variation Detecting Natural Selection Experimental methodsSuch as expe

46、rimental evolution for drug resistance using microorganismsMethods to study adaptationContribution of neutral theory for evolution Comparative methods I: dN/dSdS: synonymous differencedN: non-synonymous differenceSynonymous & non-synonymous difference between sequenceNegative (purifying) selecti

47、on: dN/dS 1 is suggestive of positive selectionEvolutionary SchemeEvolution of leptin a gene that affect body weight in miceBRCA1 in the readingComparative Methods II: McDonald-Kreitman testPolymorphism: Difference within species: N/SDivergence (fixed): Difference between species: N/SABComparative M

48、ethods II: McDonald-Kreitman testMcDonald & Kreitman, 1991Replacement = nonsynonymousabcdNeutral expectation: a/b = c/dComparative Methods III: Haplotype-based testA long-range haplotype with an unusually high frequency in a population is a signature of positive selection.Recombination Shrinks H

49、aplotypesLength of HaplotypesFrequencyHaplotype Length DistributionLength of HaplotypesFrequencyLength of HaplotypesFrequencyLength of HaplotypesFrequencyWhich one is from Africa?Selective SweepSelective SweepComplete Selective SweepRecombination Shrinks HaplotypesLength of HaplotypesFrequencyExampl

50、e I Lactose digestionObservation: In most mammals, the gene for lactose tolerance switches off once an animal matures beyond the weaning years. Most human do this as well.Populations with nomadic lifestyle in northern African and Arab or with Cattle farming history in Northern Europe or Tibet have h

51、igh frequency of lactose tolerance phenotype Tishkoff, 2007Genotyping across a 3-Mb region demonstrates haplotype extending 2.0 Mb on chromosomes carrying C-14010, consistent with a selective sweep over the past 7,000 years. Natural Selection and Variation Detecting Natural SelectionNutrition and Hu

52、man AdaptationCommon dietary chemicals can act on the human genome to alter gene expression or structure. These interactions vary depending on personal genetic makeup. Some diet-regulated genes are likely to play a role in the onset, incidence, progression, and/or severity of chronic diseases.Dietar

53、y intervention based on knowledge of nutritional requirement, nutritional status, and genotype (i.e., personalized nutrition) can be used to prevent, mitigate or cure chronic disease.“Nutrigenomics”Major Dietary Transitions in Human HistoryNeolithic RevolutionOutline Neolithic Revolution Examples of

54、 Nutritional AdaptationNeolithic Revolution The first agricultural revolution. It was the transition from hunting and gathering (Nomadic) to agriculture and settlement 10,0007000 years ago Represented by domestication of plants and animals It had big social consequences, such as social structure, di

55、sease patterns, technology development etc.1. Notice a desirable trait in a species2. Separate members of the species from nature3. Selective breeding (artificial selection)4. Exaggerate and stabilize desirable trait(s)5. Change on the biological levelShift in Food Sources over TimeEmber and Ember,

56、1996The Neolithic revolution didnt happen abruptly, but emerged gradually as a result of trial and errorIt first appeared in a few places, not everywhereMost people didnt go through it at first, and somestill haventOn the whole, agriculture was the big winner overpastoralism and hunting and gatherin

57、gNeolithic RevolutionIndependent Development vs. Cultural Diffusion Areas of Independent Development:SW Asia (wheat, pea, olive, sheep, goat)China & SE Asia (rice, millet, pig)Americas (corn, beans, potato, llama)Areas of Agriculture Through Diffusion:EuropeWest & Sub-Saharan Africa (?)Indus

58、 River Valley (rice cultivation)Neolithic RevolutionCatal HuyukModern TurkeyFirst settled:c. 7000BCEJerichoModern IsraelFirst settled:c. 7000BCENeolithic RevolutionAgriculture led to enormous productivity increases and significant population increase and density Specialization of technology and skil

59、ls developedMetal Working: From Copper to BronzeThe working of metals became very important to early human settlements for tools & weapons.Early settlements gradually shifted from copper to the stronger alloy bronze by 3,000BCEushers in the Bronze Age!Metal working spread throughout human commun

60、ities slowly as agriculture had. New social structures emergedSocial stratification/hierarchyFood producers support “non-productive” elitesCraft specialization Religious elites (priesthoods)Hereditary rulers (kings)SlaveryGender discriminationCosts & Advantages of AgricultureAdvantagesCostsSteady food suppliesGreater populationsLeads to orga

温馨提示

  • 1. 本站所有资源如无特殊说明,都需要本地电脑安装OFFICE2007和PDF阅读器。图纸软件为CAD,CAXA,PROE,UG,SolidWorks等.压缩文件请下载最新的WinRAR软件解压。
  • 2. 本站的文档不包含任何第三方提供的附件图纸等,如果需要附件,请联系上传者。文件的所有权益归上传用户所有。
  • 3. 本站RAR压缩包中若带图纸,网页内容里面会有图纸预览,若没有图纸预览就没有图纸。
  • 4. 未经权益所有人同意不得将文件中的内容挪作商业或盈利用途。
  • 5. 人人文库网仅提供信息存储空间,仅对用户上传内容的表现方式做保护处理,对用户上传分享的文档内容本身不做任何修改或编辑,并不能对任何下载内容负责。
  • 6. 下载文件中如有侵权或不适当内容,请与我们联系,我们立即纠正。
  • 7. 本站不保证下载资源的准确性、安全性和完整性, 同时也不承担用户因使用这些下载资源对自己和他人造成任何形式的伤害或损失。

评论

0/150

提交评论