Génomique comparative

Les objectifs

  1. Aide l'annotation en identifiant les régions fonctionnelles (les régions non fonctionnelles sont non conservées)
  2. Identifier le jeu de gènes de chaque organisme
  3. Comprendre les solutions trouvées par des organismes différents pour une même fonction
  4. Etudier des gènes/fonctions particuliers par comparaison de séquence (voir cours de bioinformatique)
  5. Autres questions spécifiques: adaptation, resistance, pathogénicité, etc.

Document 1:

Parasites go the full monty
PATRICK J. KEELING, Nature 414, 401–402 (22 November 2001)

Parasites are well known for stripping themselves down to the bare essentials, but how far will they go? Microsporidia are one group of single-celled parasites that have taken it to extremes and gone the 'full monty'. On page 450 of this issue1, Katinka and colleagues expose the shocking extent of this striptease in the complete genome sequence of the microsporidian Encephalitozoon cuniculi , which parasitizes a range of mammals, including humans. This genome is a mere shadow of those found in other eukaryotes (organisms with nucleated cells), as it consists of only 2.9 million base pairs — less than 0.1% the size of the human genome. This is even smaller than the genomes of many bacteria. Nevertheless, the genome is a treasure trove of information on the powerful reductive forces that shape these unusual parasites. .... Microsporidia, however, have invented a unique system of core energy metabolism. They use parts of typical mitochondrial metabolic pathways, mixed with pathways found in other organisms that lack mitochondria, resulting in a system that is fundamentally different from either1, 9 . In particular, microsporidia lack pyruvate:ferredoxin oxidoreductase — a key enzyme in other organisms that lack mitochondria, and a common target for anti-parasitic drugs — and use mitochondrial pyruvate dehydrogenase in its place1, 9. Once again, we see François Jacob's image of evolution as a tinkerer10 , using bits and pieces of existing machines to build a completely new one — in this case, something as central to life as a new form of energy metabolism.

Document 2:

Do all organisms use the same gene for the same purpose? 
The answer here is clearly "no". 
 Example: 
   2.When the genome of the archaean Methanococcus jannaschii was sequenced, four of the 20 amino-acyl-tRNA
     synthetases could not be found. 
   3.These enzymes are critical in preparing the tRNAs for protein synthesis. 
   4.Biochemical evidence indicated that glutamine and asparagine are incorporated as transamindated derivatives of
     glutamate and aspartate, so the absence of these tRNA synthetases was not surprising. 
   5.A comparable story was postulated for cysteine, hypothesizing that cysteine-tRNA is produced by trans-sulfuration
     of serine-tRNA. 
   6.But the absence of lysyl tRNA synthetase was unexplained. 
   7.Subsequently the lysine-tRNA synthetase was identified -- it is dissimilar to the other tRNA syntetases, apparently a
     new class. 
   8.Not the product of rapid evolution. 
   9.The bacteriuim Borrelia burgdorferi was subsequently found to have the same kind of lysine-tRNA synthetase as
     that found in M. jannaschii 
  10.Likely explanations: 
     1.Parallel evolution 
     2.Horizontal gene transfer & substitution 

E. coli K12 - 0157:H7 (Nature, 409, 529-533, 2001)