tracking the genetic legacy of past human populations through the grid
DESCRIPTION
Tracking the genetic legacy of past human populations through the grid. Nicolas Ray University of Geneva & UNEP/GRID-Europe. Swiss Grid Day, Bern, November 26 th 2009. Adapted from Cavalli-Sforza & Feldman, 2003. Human migrations. [12,000]. [55,000]. Homo sapiens sapiens. - PowerPoint PPT PresentationTRANSCRIPT
Swiss Grid Day, Bern, November 26th 2009
Human migrationsHuman migrations
Adapted from Cavalli-Sforza & Feldman, 2003
[12,000]
[55,000]
Homo sapiens sapiens
1. Better understand human evolution
• Origin of modern human (when, where, how many?)
• Relationship with other members of the Homo genus
2. Distinguish between the effect of demography and those
of selection (biomedical applications)
Why aiming at a good demographic Why aiming at a good demographic modelmodel
Gene-specific factorsmutationsrecombinationselection
A complex past demographyfluctuation in effective pop. sizesubstructuremigrations
Observed patterns of genetic diversity in contemporary populations
A complex demographyA complex demography
Adapted from Cavalli-Sforza & Feldman, 2003
[10,000]
[55,000]
demographic and spatial expansions
population bottlenecks
fast migration events
population isolation
secondary contacts
SPLATCHESPLATCHESPatiaL And Temporal Coalescences in Heterogeneous Environment
(http://cmpg.unibe.ch/software/splatche)
From environment to demographyFrom environment to demography
Spatial resolution: 100 km
low
high
Carrying capacity
low
high
Friction
From environment to demographyFrom environment to demography
Demographic simulationsDemographic simulations
stepping-stone model (cellular automata)
Cell or deme
Pop
. si
ze
time
Demography and spatial expansionDemography and spatial expansion
Population density
Genetic simulationsGenetic simulations
Simulated genealogySimulated genealogy
MutationModèle de mutation
AC
CTA
GTA
CA
ATC
GG
TA
ATG
CC
ATTG
GT
TCCTTGTA…ATTGGT
ACCGAGTA…GTTGGT
Summary statistics– Within population:
• S, – Between populations
• Pairwise FST
• Global FST
– Globally• S,
1-10 mio.
Computer clusters
UBELIX (>500 nodes)
Zooblythii (~40 nodes)
APPROXIMATE BAYESIAN APPROXIMATE BAYESIAN COMPUTATIONS (ABC) COMPUTATIONAL COMPUTATIONS (ABC) COMPUTATIONAL ISSUESISSUES
Computational issuesComputational issues
A fully spatially-explicit model using 500 loci in 800 individuals:
10 CPU-years
Adding long-distance dispersal:
20 CPU-years
SPLATCHE on the gridSPLATCHE on the grid
early 2005: joined the Biomed VO of the EGEE project
mid 2005: tested on GILDA test bed, and deployed on the Grid
since mid 2006: production mode and optimization
Use of SPLATCHE on the gridUse of SPLATCHE on the grid
N simulations
Independent simulations: - the more CPUs, the better- job failures are not that bad
GRID
Posterior distribution of demographic/genetic parameters of interest
Statistical tools
OptimizationsOptimizations
5 mio. simulations
GRID
Reduction of the number of simulations (Daniel Wegmann)By MCMC. Promising results (~50 times less sims)
Submission timemulti-threaded application using up to 30 RBs (used for the WISDOM project)
Fetching time of job outputsin-house multi-threaded solution for checking status and getting outputs
Geographic origin of human dispersalGeographic origin of human dispersal
Ray et al. (2005) Genome Research
Interactions among populationsInteractions among populations
Interaction between modern humans and Neanderthals in Europe
Currat & Excoffier (2004), PLoS Biol.
Plausible introduction site 1LAGOON CREEK (first sight: 1979)
Initial introduction site in AustraliaGORDONVALE (1935)
KDM
NW
B
T
RE
120 0 120 240 360Kilometers
19991982
19881992
1995
1996
1997
1998
Plausible introduction site 2NORMANTON (first sight: 1964)
Cane toad invasion in AustraliaCane toad invasion in Australia
Estoup, A., Baird, S. J. E., Ray, N., Currat, M., Cornuet, J.-M., Santos, F., Beaumont, M. A. and L. Excoffier. Combining genetic, historical and geographic data to reconstruct the dynamics of the bioinvasion of cane toad Bufo marinus. Submitted
Take-home messageTake-home message