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Supplementary Data
Additional Evolutionary Analyses of KLF14
In addition to the pairwise (single human haplotype versus primates) analyses presented in the Results, we simultaneously investigated whether there was significant elevation in the human dN/dS using all of the human haplotypes. For this analysis we created a haplotype tree using the neighbour-joining method within MEGA3 ADDIN EN.CITE Kumar200439639617Kumar, S.Tamura, K.Nei, M.Life Sciences A-351, The Biodesign Institute, Tempe, AZ 85287-4501, USA. s.kumar@asu.eduMEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignmentBrief BioinformBrief Bioinform150-6352Databases, Genetic*Evolution, MolecularInternetPhylogenyResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.*Sequence Alignment/methodsSequence Analysis, DNASequence Analysis, Protein*Software2004Jun15260895http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15260895 [72]. One caveat is that this haplotype tree does not represent the true evolution of the haplotypes. Due to the diploid nature of DNA, haplotypes often evolve by recombination, as well as mutation. As a result, the tree constructed by this analysis is a similarity tree, which we assumed as a best guess for the evolution of the haplotypes. We used PAML ADDIN EN.CITE Yang199838238217Yang, Z.Department of Biology, University College, London, United Kingdom. z.yang@ucl.ac.ukLikelihood ratio tests for detecting positive selection and application to primate lysozyme evolutionMol Biol EvolMol Biol Evol568-73155Animals*Evolution, Molecular*Likelihood FunctionsModels, BiologicalMuramidase/*physiologyPrimates/*physiology*Selection (Genetics)Variation (Genetics)1998May9580986http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9580986 [39] to investigate whether there is evidence for positive selection in the branches of the haplotype tree. Multiple two-ratio and three-ratio tests were performed (data not shown). Although some lineages had dN/dS values that suggested positive selection, they were not significantly >1 when tested using the likelihood ratio test.
We also used PAML to look for positive selection at individual amino acid sites within specific lineages of the human haplotype tree ADDIN EN.CITE Yang200039739717Yang, Z.Nielsen, R.Goldman, N.Pedersen, A. M.Department of Biology, University College London, London NW1 2HE, United Kingdom. z.yang@ucl.ac.ukCodon-substitution models for heterogeneous selection pressure at amino acid sitesGeneticsGenetics431-491551Amino Acid Substitution*Amino AcidsAnimals*CodonDrosophila/geneticsGene Products, vif/geneticsGenes, polGlobins/geneticsHIV Envelope Protein gp120/geneticsHemagglutinin Glycoproteins, Influenza Virus/geneticsHumansMembrane Glycoproteins/geneticsMitochondria*Models, GeneticPeptide Fragments/geneticsResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.*Selection (Genetics)Vertebrates/geneticsViral Envelope Proteins/geneticsViral Nonstructural Proteins/genetics2000May10790415http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10790415 Yang200239839817Yang, Z.Nielsen, R.Galton Laboratory, Department of Biology, University College London. z.yang@ucl.ac.ukCodon-substitution models for detecting molecular adaptation at individual sites along specific lineagesMol Biol EvolMol Biol Evol908-17196Angiosperms/geneticsAnimalsCodon/*genetics*Evolution, MolecularGenes, BRCA1HumansLikelihood Functions*Models, Genetic*Multigene FamilyMuramidase/genetics*MutationPhylogenyPhytochrome/geneticsPrimates/geneticsResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.2002Jun12032247http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12032247 [77,78]. Multiple models that look for variable dN/dS ratios among sites within lineages did not detect sites that showed significant evidence for positive selection using the likelihood ratio test. Thus, our extensive searches for positive selection using PAMLs maximum likelihood methods did not yield significant results. We are therefore unable to reject the hypothesis of neutral evolution in the human lineage.
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