Reading: Text 223-236Molecular Evolution: HandoutI. Introduction.Zoology 445 Fall 2006Reading: Text 223-236Molecular Evolution: HandoutI. Introduction.Molecular evolution = Change in nucleotide sequence DNA or amino acid sequence among species = Substitutions in DNA or amino acid sequence.AM Jarosz 1Zol 445 JaroszComparison of the α and  chains showed same pattern:Number of amino acid changesHuman α versus Human  85Carp α versus Human  88Shark α versus Shark  88II. Pattern of DNA substitutions.II. Drift as an explanation. Beginning in the late 1970s Kimura and Crow proposed that the pattern of substitutions was consistent with genetic drift. Their Argument:1. Synonymous substitutions do not affect phenotype. Thus, they are selectively neutral.2. Most mutations that change amino acid sequence are deleterious, AND selection purges them very quickly.3. Genetic drift predicts a constant rate of substitution.a. The chance of a neutral mutation appearing in a population is = 2N where  is the rate at which neutral mutations occur. N is the number of individuals in a population.b. Probability of fixation of that neutral mutation = 1/2NThe rate of substitution = rate at which neutral mutation occur * probability of fixation = 2N * 1/2N = If the neutral mutation rate stays constant, then the rate of substitutions due to drift will be constant.2Zol 445 JaroszIII. Selectionists Counter-argumentA. Measuring rates of substitution is on a per generation basis.IV. Nearly Neutral Model that speculates that some substitutions are fixed by drift even when they are weakly selected against. When s  (1/2Ne) then an allele is effectively neutral even though there is some selection against it.Fig 6.22V. Additional counter-arguments by selectionists. A. Codon Bias Figure 6.24Yeast E. coliB. Some data suggest that non-synonymous replacements are due to positive selection.Detecting positive selection:dN/dS < 1 then most non-synonymous mutations are deleterious. Selection acts to purge them from the species. Those fixed are due to drift because they are neutral or weakly selected against.dN/dS = 1 then non-synonymous mutations are fixed as if they were neutral.dN/dS > 1 then non-synonymous mutations are advantageous and are fixed by positive selection.Where: DN = rate at which non-synonymous mutations are fixed.DS = rate at which synonymous mutations are fixed.3Zol 445 JaroszFig 6.23Conclusion: 1. Molecular evolution is undoubtedly caused by the interaction between mutation rates, genetic drift & selection. 2. Too early to generalize on the relative importance of drift and selection in molecular evolution.\Evolution Zol 445\2006\Molecular Evolution