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Studying functional diversification and evolution of regulatory sequences after a gene duplication event
Perspectives of extension of this common project to a more ambitious proposal to be submitted to funding agencies : Long term Added value of the cooperation : The Toulouse group has initiated the study of the Ly6 superfamily in Drosophila, and has a strong background in cell biology, imaging technologies (Plateforme Imagerie RIO) and genetics. The Lisboa group is specialised in the study of evolution of genetic networks, dissection of gene regulatory elements and harbours populations of Tribolium and Ceratitis that are necessary for the study of the Ly6 ancestral genes (see below). Thus, the whole project is dependent on the exchange of researchers and skills sharing between the two institutions.
Summary of the proposal :
The profusion of gene paralogues (gene families) that we observe in all metazoan genomes is the signature of the many gene duplication events that took place in the course of evolution. It has been postulated that only when a redundant gene locus is created by duplication it can accumulate formerly “forbidden” mutations affecting both their coding and regulatory sequences, permitting evolution of new genetic functions. Our proposal addresses a fundamental question in biology that ties genome evolution to phenotypic variation through the modulation of developmental programmes: what is the molecular basis for evolution of regulatory enhancers after gene duplication?
For this, we have chosen to study a novel family of Drosophila paralogues recently described by us, and whose members code for different anchored proteins sharing an extracellular motif called Ly6 domain. We have shown that the Drosophila genome encodes for 35 members of this family, which are often grouped in genomic clusters. Preliminary characterisation by the Toulouse partner of their diverse expression patterns indicates that their enhancers and regulatory regions have undergone extensive changes. Our phylogenetic analysis indicates that the Ly6 family has considerably fewer members in other insects: for instance, there are only 11 in the beetle Tribolium. Gene phylogeny reconstruction indicates that several of the Drosophila Ly6 paralogues have arisen very recently on an evolutionary scale (<100 My) by gene duplication.
We will focus on the analysis of a reduced set of Ly6 genes (6 contiguous genes) that have duplicated during the evolution of the drosophilid lineage from a common ancestor that will be characterised in two different species: Tribolium castaneum and, in an intermediate stage, the fly Ceratitis capitata. The requested funding will permit to carry out the characterisation in the laboratory of the Lisboa partner of the expression patterns of the ancestral Ly6 members in Tribolium and Ceratitis, to compare the expression data obtained and prepare a manuscript for publication containing this information and our phylogenetic analysis of the family. After publication of this seminal work, financial aid will be requested from Portuguese, French and European funding bodies for an ambitious joint project that will focus on: 1) Comparing the roles of each single Drosophila Ly6 paralogues with the role of their orthologues (evaluation of sub- or neofunctionalization processes) and 2) Analysing the divergence of their promoter sequences (conservation and/or co-option of specific regulatory modules).
Antonio PINEDA-LUCENA, Valencia Claudio GOMES, Lisboa
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