Melvin's digital garden

Reconstructing the evolutionary history of mammalian genomes

CREATED: 200906290232 ** Background

  • blocks comparing human and mouse genomes (source: US DOE)
  • information provided by reconstructed ancestral genomes ** ACYL3, gene lost in human and chimp [[Zhu2007]] ** Human accelerated region 1 [[Pollard2006]]
  • base level reconstruction is fairly accurate given good alignments
  • challenge is chromosomal rearrangements: inversion, translocation, fission, fusion
  • using experimental chromosome painting technique [[Froenicke2006]] ** CARs
  • discrepancy between MGR and chromosome painting result, see Murphy2005, Bourque2005, Froenicke2006, due to differences in resolution, coverage
  • alignment, then partition genomes into synteny blocks (maximum span of homologous blocks whose order and orientation are conserved, may contain large insertions/deletion but no rearrangements) [[Kent2003]]
  • algorithm for contiguous ancestral regions, similar to Fitch’s algorithm, reduces to maximum bipartite path cover problem [[Ma2006]]
  • extend CAR method to include duplications ** Determining the actual operations
  • infinite sites model has an efficient algorithm to reconstruct species tree and ancestral genomes [[Ma2008]]
  • operations allowed: 2-breakpoint operations (DCJ), 3-breakpoint operations, tandem duplication
  • assumptions: exact same breakpoint is never used twice, in each segment there are infinitely many neutrally evolving sites so all pairs of homologus segments can be found and exact distances computed
  • reverse evolution algorithm

find homologous segments (atoms)

build evolutionary trees for atoms

create unified tree for all speciation and duplications

build breakpoint graph

determine when each operation happened

reverse evolution and fill-in

** Open problems

  • application to genome assembly
  • biological implications of the structural changes happened on the branch towards humans
  • study cancer evolution [[Hampton2009]]