milton_1992_HIV_DvsL

milton_1992_HIV_DvsL - observed-3/2powerdependenceofprob-...

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Unformatted text preview: observed-3/2powerdependenceofprob- abilityongaplength. The final outcome of the exhaustive matchingisareorganizeddatabasethatcan berapidlysearched using the DARWIN (DataAnalysisandRetrievalWithIndexed Nucleotide/Peptide Sequences) system (19).Eachofthe1.7x 106alignedpairsof subsequencesthatresultfromtheexhaus- tive matchingischaracterizedbyanevolu- tionarydistancemeasured inPAM units. DARWIN, takingaPAM distance from the user, rapidly reconstructs the entire databaseintheformofsetsof"connected components," entries joinedbyamatch witheveryotherentryinthecomponentat orbelowthe user-designatedPAM.Because thePAM distancesare accompaniedbya statisticalvariance,evolutionarytrees(20, 21) constructed from these distances by DARWIN arerigorous;theyareaccompa- niedby aprobability scoreforthemost probable connectivity, probabilistic se- quences fortheancestralproteinsatthe nodesofthetree,andamultiplealignment. At very lowPAM distances,thecon- nected components include very similar sequences, multipleentriesinthedatabase, andentriesthatdiffer onlybecauseof se- quencing or entry error. At increasing PAM distances,however,connectedcom- ponentsgrowtoincludefamiliesandsuper- familiesofproteins.Repetitivesequences arethe onlyfeaturethatsignificantlyjoins apparently nonhomologous entries into connected components. From the total numberofconnectedcomponentsplotted asafunctionofPAM distance(Fig.4),the numberofdifferentproteintypesinthe databasecanbe estimated.Evenconserva- tive estimates indicate the existence of severalthousandseparatefamiliesofpro- teins (8). Finally,from theseconnected components,proteins andmetabolismscan bereconstructedforvariousancestorsof modem organisms (10). Several ofthese reconstructedancient proteinshave now been preparedandstudiedintheselabora- tories(22). REFERENCES AND NOTES 1. R.F.Doolittle,Science214,149 (1981). 2.A.W. F.Edwards and L.L.Cavalli-Sforza,Ann. Hum. Genet. 27, 104 (1963); E. Zuckerkandl, ProtidesBiol.Fluids12,102(1964); andL. Pauling,inEvolvingGenesandProteins,V.Bry- sonandH.J.Vogel,Eds.(AcademicPress,New York,1965),p.97;J.S.Farris,Syst.Zool.19,83 (1970);W.Fitch,ibid.20,406(1971). 3. R. F. Doolittle, Ed., Methods Enzymol. 183, 1 (1990). 4. S.A. Benner,Adv.EnzymeRegul.28,219(1989); _ andD.Gerloff,ibid.31,121 (1991). 5. D.R.Knightonetal.,Science 253,407(1991);J. M. Thornton, T. P. Flores, D. T. Jones, M. B. Swindells,Nature354,105(1991). 6.T.NiermannandK.Kirschner,Protein Eng.4,137 (1990). 7.T.L.Blundell,B.L. Sibanda,M.J.E.Stemberg, J.M.Thomton, Nature326,347(1987). 8.W.R.Taylor,MethodsEnzymol.183,456(1990); R.L.Doritetal.,Science250,1377(1990). 9.T.D.Yager,D.A.Nickerson,L.E.Hood, Trends Biochem.Sci.16,454(1991);M.C.Rechsteiner, ibid.,p.455....
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This note was uploaded on 05/28/2010 for the course WE BIBI010000 taught by Professor Marnikvuylsteke during the Spring '10 term at Ghent University.

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milton_1992_HIV_DvsL - observed-3/2powerdependenceofprob-...

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