Protein Evolution: Structure, Function, and Human Health

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Guest Lecture, Protein Biochemistry course on basics of evolution at the protein level and some applications.

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Protein Evolution: Structure, Function, and Human Health

  1. 1. Protein  Evolu-on   Structure,  Func-on,  and  Human   Health   11/28/2013   Dr.  Daniel  Gaston,  Department   of  Pathology   1  
  2. 2. So,  about  this  evolu-on  thing?   Why  should  I  care?  What  use  is  it?  
  3. 3. Lots  of  reasons   •  Knowledge  for  its  own  sake  is  good   –  Otherwise,  why  do  science  at  all?  
  4. 4. Lots  of  reasons   •  Knowledge  for  its  own  sake  is  good   –  Otherwise,  why  do  science  at  all?   •  Shapes  our  understanding  of  ecology  and   biological  diversity  
  5. 5. Lots  of  reasons   •  Knowledge  for  its  own  sake  is  good   –  Otherwise,  why  do  science  at  all?   •  Shapes  our  understanding  of  ecology  and   biological  diversity   •  Prac-cal  reasons   –  An-bio-c  resistance   –  Microbiome:  Fecal  transplanta-on   –  Cancer   –  Predic-ng  gene/protein  func-on   –  Predic-ng  the  impact  of  muta-ons  for  poten-al  to   cause  human  disease  (Genotype:Phenotype)  
  6. 6. Evolu-on  of  Life  on  Earth   A  (Very)  Brief  Overview  
  7. 7. Eukaryota" Eubacteria" Archaebacteria" ROOT Iwabe et al. 1989 Gogarten et al. 1989
  8. 8. Eukaryota" Eubacteria" Archaebacteria" ROOT Iwabe et al. 1989 Gogarten et al. 1989
  9. 9. Eukaryota" Eubacteria" Archaebacteria" ROOT Iwabe et al. 1989 Gogarten et al. 1989
  10. 10. You  are  here  
  11. 11. A  Brief  History  of  Cells  and  Molecules   •  Origin of the earth ~4.5 billion years ago •  Origin of life: ~3.0-4.0 billion years ago –  –  –  –  –  Origin of self-replicating entities The RNA world (?) Origin of the first genes, proteins & membranes Gave rise to the first cells the Last Universal Common Ancestor (LUCA) of all cells –  Probably had 500-1000 genes •  First microfossils of bacteria: ~3.5 billion years ago (controversial) ~2.7 billion years ago (for certain) •  Oxygenation of the atmosphere: 2.3-2.4 billion years ago (by photosynthetic bacteria) •  Origin of eukaryotes: ~1.0-2.2 billion years ago (probably 1.5) •  Origin of animals: ~0.6-1.0 billion years ago
  12. 12. Some  Defini-ons   •  Homology = descent from a common ancestor –  homology is all or nothing: sequences are either homologous (related) or not homologous (not related) –  Not the same as “similarity” (degrees of similarity are possible)
  13. 13. Some  Defini-ons   •  Divergence = change in two sequences over time (after splitting from a common ancestor) Ancestral sequence T Sequence 1 T Sequence 2 •  Convergence = similarity due to independent evolutionary events –  On the amino acid sequence level, it is relatively rare & difficult to prove (but see an example later)
  14. 14. How does evolutionary change happen in proteins?
  15. 15. Evolu-on:  Two  Groups  of  Processes   •  Muta-on   –  Many  different  processes  that  generate  muta-ons   –  Muta-ons  are  the  raw  materials  needed  for   evolu-on  to  happen   •  Selec-on  and  DriY   –  Muta-ons  happen  in  individuals   –  Evolu-on  happens  in  popula-ons  of  organisms   –  Selec-on  and  Gene-c  DriY  affect  the  frequency  of   muta-ons  in  a  popula-on  over  -me  
  16. 16. Muta-ons  
  17. 17. Point  Muta-ons Unrepaired mispaired base ! ! ! ! AGGTTCCAATTAA! TCCAAGGTCAATT! ! REPLICATION (meiotic or mitotic division) ! AGGTTCCAATTAA ! AGGTTCCAGTTAA ! TCCAAGGTCAATT! TCCAAGGTTAATT! Wild-type alleles ! Mutant allele Mutant Gamete (for multicellular org.) Wild-type Gamete (for multicellular org.)
  18. 18. AGTCCAAGGCCTTAA -------------> AGTTCAAGGCCTTAA point mutation

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