I.  The Molecular Clock

    A.  Example of molecular evolution: cytochrome C

    B.  Molecular clocks

        1.  Example: molecular clock for  a globin.
 
 

 a.  Time axis is in millions of years
 b.  Each point represents a comparison
      of the indicated species with humans.
 
 
 
 
 
 
 
 
 
 
 

            2.  Mamalian proteins.
 
 

    A.   The Neutralist View.

        1.  The Neutralist view maintains that most protein evolution is due to genetic drift.

        2.  Most mutations are deleterious, and are therefore eliminated by natural selection as soon
                 as they occur.
        3.  Some mutations have negligible effect on fitness, and are therefore effectively neutral. A small
                 but real fraction of these mutations will be fixed by genetic drift and thus cause evolutionary
                 change in protein sequence.
        4.  Mutations that are advantageous are very rare, because organisms are close to optimally
                 adapted and therefore very few "improvments" can be made.

    B.  The Selectionist View

        1.  The Selectionist view maintains that most protein evolution is due to natural selection.

        2.   Most mutations are deleterious, and are therefore eliminated by natural selection as soon
                 as they occur.
        3.  Relatively few mutations have negligible effects on fitness, and are thereby effectively
                 neutral and governed by drift.
        4.  A substantial number of mutations are selectively advantageou and are fixed by natural
                 selection when they arise.  These mutations account for most protein evolution.

     C.  Nature of the disagreement: enzyme functioning
 
 
 

Three-dimensional structure of the enzyme hexokinase.  In (a) the active site of the enzyme lies in the center groove.  (b) portrays the substrate, glucose, in the active site.  Note that complexing with substrate causes a change in enzyme configuration.  (From N. A. Campbell.  1990.  Biology.  Benjamin/Cummings.)
 
 
 
 
 
 
 
 
 
 

III.  Distinguishing between Neutralist and Selectionist Views--The Molecular Clock.

    A.  Explanation of the Molecular Clock by the Neutralists.

        1.  The molecular clock follows directly from the properties of genetic drift

        2.  The rate of fixation of new mutations is just

                    Mutations fixed/generation = (New mutations/generation)  x    (Prob. of fixation)

                                                             = (2N x  m) x  (1/2N)

                                                             =    m .

    B.  Explanation of the Molecular Clock by the Selectionists--unsatisfactory and ad hoc.
 

IV.  Distinguishing between Selectionist and Neutralist Views: Examples of Adaptation

    A.  Example:  Evolution of insulin in rodents.
 

Schematic portrayal of pig insulin monomer.  The location of some of the amino-acid changes separating pigs from guinea pigs are indicated.  Note that many of the changes have occurred in the region of dimer contact. (From J. H. Gillespie.  1991.  The Causes of Molecular Evolution.  Cambridge Univ. Press)
 
 
 
 
 
 
 
 
 
 
 
 
 

Numbers of amino acid substitutions separating the insulin sequence of several species.  The Histricomorph rodents are those surrounded by the dashed line.  Note the greatly accelerated rate of amino-acid substitution in this group, compared to the 3 substitutions separating mouse and pig.  (From J. H. Gillespie.  1991.  The Causes of Molecular Evolution.  Cambridge Univ. Press)
 
 
 
 
 
 
 
 

    B.  Example: Lysozyme
 

Left: phylogeny of pigs and artiodactyls showing accelerated rate of amino-acid substitution in lysozyme between points A and B.  Right:  phylogeny of primates, showing accelerated rate of substitution in Langurs. (From J. H. Gillespie.  1991.  The Causes of Molecular Evolution.  Cambridge Univ. Press)
 
 

    C.  Conclusions

        1.  There are many good examples of adaptive amino-acid substitution, which suggests that much
             protein sequence evolution may be caused by natural selection.

        2.  However, a list of examples can not definitively prove that most amino-acid substitutions occur
             due to selection rather than drift.  One can always claim that the examples aren't representative and
             constitute exceptions to the general pattern.

        3.  Consequently, other methods must be used to distinguish between the neutralist and selectionist