Over the past decades the study of induced mutants has revealed major genes affecting lifespan and aging in the fly Drosophila melanogaster and the worm Caenorhabditis elegans. But so far it is unclear if and how gene regulation changes with age and how this is affected by natural variation. High-throughput gene transcription profiling in mutant and wildtype worms and flies showed that gene transcription variation did not decrease with age, suggesting that gene regulation remains constant throughout life. But currently detailed insight into genome-wide regulatory patterns in aging organisms is lacking. Here we present the first study of the temporal dynamics of global gene transcription regulation in a recombinant inbred line population of aging worms. These SNP genotyped recombinant inbred lines (RILs) were derived from a cross between two of the most genetically divergent wildtypes N2 and CB4856. We extracted mRNA from juvenile, reproductive and old worms and measured genome-wide gene expression in all RILs using 60 mer microarrays. In addition we measured average lifespan for all RILs. Genetic mapping of gene transcription (eQTL) revealed age specific as well as age independent eQTLs. The number of eQTL and their effect decreased with age. But the effect of a few eQTL increased with age indicating “old-age” specific transcription regulation. These age dependent transcripts have a different temporal expressiondepending on which parental allele harboring the age eQTL is present. Research is ongoing to see if these time-dependent eQTLs can explain the genetic variation in lifespan across the CB4856 x N2 RILs.
|Title of host publication||European Conference on Complex Systems' 09, Warwick, UK, 21-25 September 2009|
|Place of Publication||Warwick|
|Publication status||Published - 2009|
|Event||European Conference on Complex Systems' 09, GENSYS satellite meeting, Warwick, UK, 21-25 September 2009 - |
Duration: 21 Sep 2009 → 25 Sep 2009
|Conference||European Conference on Complex Systems' 09, GENSYS satellite meeting, Warwick, UK, 21-25 September 2009|
|Period||21/09/09 → 25/09/09|