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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Genetic architecture in Drosophila - The role of the Y chromosome in gene expression across the genome.

Tildelt: kr 3,2 mill.

Understanding genetic architecture, the underlying basis of phenotypic traits, and its relationship to evolutionary change, is a major challenge for evolutionary biologists. Variation in gene expression is one of the most important factors causing phenoty pic variation. We will study the role of the Y chromosome of Drosophila melanogaster in regulation of gene expression on the X chromosome and the autosomes. Widespread regulatory effects of the Y chromosome was discovered in a study published in Science i n 2008 by the Hartl laboratory at Harvard University using Y chromosomes from different populations in the same genetic background and measuring the difference in gene expression. The discovery of Y-linked regulatory variation (YRV) on a genome-wide scale is a new phenomenon that motivates studies of its mechanisms, adaptive significance, and evolutionary dynamics. Our hypothesis is that the polymorphic Y chromosome differs in the number of binding sites that compete with YRV-responsive genes for chromati n-associated proteins that are present in limited amounts in the cells. These binding sites are most likely repetitive sequences that make up the majority of the heterochromatic Y chromosome. We aim to: A) Identify which region(s) on the Y that participat es in the regulation of genes on the X chromosome and the autosomes; B) Develop markers to measure differences in repetitive sequences on the Y; C) Test the involvement of known regulatory pathways in YRV, especially the pathway mediated by suppressors o f PEV (position effect variegation) and that mediated by repeat-associated small inhibitory RNA (rasiRNA); D) Determine which genes are differentially affected by polymorphic Y present in XXY females. Arguing in favor of our hypothesis is the known high d egree of polymorphism in rDNA and Su(Ste) repeats, the effect of the Y chromosome in modulating PEV, and the specificity of binding of key chromatin-associated proteins with microsat sequences on the Y.


FRIMEDBIO-Fri prosj.st. med.,helse,biol