Molecular EvolutionEvolution using moleculesSome important dates in history (billions of years ago)PowerPoint PresentationTwo important early observationsSlide 6Different rates of change for different proteinsRates of change in protein familiesBeta-globins (orthologues)Beta-globins Uncorrected pairwise distancesBeta-globins Corrected pairwise distancesUPGMA treeSlide 13Alu sequences Uncorrected pairwise distancesAlu sequences Corrected pairwise distancesCorrecting distances between DNA and protein sequencesThe Jukes-Cantor model of nucleotide substitutionA simple 4-state Markov chain: the Kimura 2-parameter model for nucleotide changeMarkov chainThe multiplication ruleContinuous-time versionInterpretation of QSlide 23Jukes-Cantor model (1969)Slide 25Evolutionary time, PAMDistance adjustmentSlide 28Slide 29IllustrationCorrespondence between observed a.a. differences and the evolutionary distance (Dayhoff et al., 1978)The stationary distributionReversibilityProofBelow diagonal: BLOSUM62 substitution matrix Above diagonal: Difference matrix obtained by subracting the PAM 160 matrix entrywise. From Henikoff & Henikoff 1992PAM matricesSlide 37Slide 38Slide 39Slide 40BLOck SUbstitution Matrices (BLOSUM)Matrices at different distancesSlide 43How did variations arise?Modeling DNA base substitutionA pair of homologous basesMore assumptionsNew pictureJoint probability of A and CEstimating distance of two sequencesM pairsOne simple methodSlide 531Molecular EvolutionStat 246, Spring 2002, Week 6a2Evolution using molecules•Our DNA is inherited from our parents more or less unchanged.•Molecular evolution is dominated by mutations that are neutral from the standpoint of natural selection.•Mutations accumulate at fairly steady rates in surviving lineages.•We can study the evolution of (macro) molecules and reconstruct the evolutionary history of organisms using their molecules.3Some important dates in history(billions of years ago)Origin of the universe 15 4Formation of the solar system 4.6First self-replicating system 3.5 0.5Prokaryotic-eukaryotic divergence 1.8 0.3Plant-animal divergence 1.0Invertebrate-vertebrate divergence 0.5Mammalian radiation beginning 0.186 CSH Doolittle et al.45Two important early observationsDifferent proteins evolve at different rates, and this seems more or less independent of the host organism, including its generation time.It is necessary to adjust the observed percent difference between two homologous proteins to get a distance more or less linearly related to the time since their common ancestor.6Evolution ofthe globinsHemoglobinFibrinopeptides1.1 MY5.8 MYCytochrome c20.0 MYSeparation of ancestorsof plants and animals12346789105MammalsBirds/ReptilesReptiles/FishCarp/LampreyMammals/ReptilesV ertebrates/Insectsa220200180160140120100806040200200100 300 400 500 600 700 800Millions of years since divergenceAfter Dickerson (1971)Corrected amino acid changes per 100 residues900 1000 1100 1200 1300 1400bcde f h ig jHuronianAlgonkianCambrianOrdovicianSilurianDevonianPermianTriassicJurassicCretaceousPaleoceneOligoceneMiocenePlioceneEoceneCarboniferousRates of macromolecular evolution7Protein PAMsa/100 residues Theoretical 108 years lookback timebPseudogenes 400 45cFibrinopeptides 90 200cLactalbumins 27 670cLysozymes 24 750cRibonucleases 21 850cHemoglobins 12 1.5dAcid proteases 8 2.3dTriosephosphate isomerase 3 6dPhosphoglyceraldehyde dehydrogenase 2 9dGlutamate dehydrogenase 1 18d______________________________________________________________________________________aPAMs, Accepted point mutations.bUseful lookback time = 360 PAMs.cMillion years.dBillion years. Doolittle 1986 Different rates of change for different proteins8Rates of change in protein familiesProtein RateaProtein RateFibrinopeptides 90 Thyrotropin beta chain 7.4Growth hormone 37 Parathyrin 7.3Ig kappa chain C region 37 Parvalbumin 7.0Kappa casein 33 BPTI Protease inhibitors 6.2Ig gamma chain C region 31 Trypsin 5.9Lutropin beta chain 30 Melanotropin beta 5.6Ig lambda chain C region 27 Alpha crystallin A chain 5.0Complement C3a 27 Endorphin 4.8Lactalbumin 27 Cytochrome b54.5Epidermal growth factor 26 Insulin 4.4Somatotropin 25 Calcitonin 4.3Pancreatic ribonuclease 21 Neurophysin 2 3.6Lipotropin beta 21 Plastocyanin 3.5Haptoglobin alpha chain 20 Lactate dehydrogenase 3.4Serum albumin 19 Adenylate cyclase 3.2Phospholipase A219 Triosephosphate isomerase 2.8Protease inhibitor PST1 type 18 Vasoactive intestinal peptide 2.6Prolactin 17 Corticotropin 2.5Pancreatic hormone 17 Glyceraldehyde 3-P DH 2.2Carbonic anydrase C 16 Cytochrome C 2.2Lutropin alpha chain 16 Plant ferredoxin 1.9Hemoglobin alpha chain 12 Collagen 1.7Hemoglobin beta chain 12 Troponin C, skeletal muscle 1.5Lipid-binding protein A-II 10 Alpha crystallin B-chain 1.5Gastrin 9.8 Glucagon 1.2Animal lysozyme 9.8 Glutamate DH 0.9 Myoglobin 8.9 Histone H2B 0.9Amyloid A 8.7 Histone H2A 0.5Nerve growth factor 8.5 Histone H3 0.14Acid proteases 8.4 Ubiquitin 0.1Myelin basic protein 7.4 Histone H4 0.1apercent/100My From (Nei, 1987; Dayhoff et al., 1978)9Beta-globins (orthologues)10 20 30 40M V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L L V V Y P W T Q BG-human- . . . . . . . . N . . . T . . . . . . . . . . . . . . . . . . . . . . . . . . BG-macaque- - M . . A . . . A . . . . F . . . . K . . . . . . . . . . . . . . . . . . . . BG-bovine- . . . S G G . . . . . . N . . . . . . I N . L . . . . . . . . . . . . . . . . BG-platypus. . . W . A . . . Q L I . G . . . . . . . A . C . A . . . A . . . I . . . . . . BG-chicken- . . W S E V . L H E I . T T . K S I D K H S L . A K . . A . M F I . . . . . T BG-shark50 60 70 80R F F E S F G D L S T P D A V M G N P K V K A H G K K V L G A F S D G L A H L D BG-human. . . . . . . . . . S . . . . . . . . . . . . . . . . . . . . . . . . . N . . . BG-macaque. . . . . . . . . . . A . . . . N . . . . . . . . . . . . D S . . N . M K . . . BG-bovine. . . . A . . . . . S A G
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