Molecular Evolution of Proteins

 

1.  DNA bases can mutate by random processes producing amino acid changes

·      Oxidation

·      Deaminations

·      Replication problems

 

2. Effect of mutation on the protein

 

·      Some mutations are neutral, for example Asn for Asp on a surface loop

·      Some may be deleterious and may inactivate the protein

Catalytic residues, say Ser in catalytic triad of trypsin and many others

Folding residues – conversion of a core Leu to Arg may prevent folding

·      Some mutations may improve a protein, either mechanistically, structurally or for regulation.  Hemoglobins will be covered in class

 

3.  A common ancestor may give rise to several separate breeding populations, each under different selective stresses and with different chance alterations.  The protein sequences may diverge and the longer they have been separated, the greater the sequence differences will be.

·      Plant Chitinase are closely related and show abut 75% sequence identity

·      RIPs are clearly related, but only key residues are left invariant; overall identity is only about 25% between species

·      Chitinases and lysozymes have no statistically significant relationship, but 3D structure is more conservative and shows ancient peptide fold.

 

4.  Sequences can be aligned and patterns discerned

·      look for identical sequence runs

·      catalytic residues are conserved

·      Hydrophobic core is conserved, as to type (Leu . Ile . Val etc)

·      Gly and Pro are often conserved to allow turns and helix boundaries

·      Insertions and deletions often occur on surface loops