Regulatory and functional evolution upon gene duplication – EVOGENDUP

We use the fruit fly Drosophila and its sib species as a model system for understanding how genomes have been shaped during evolution. We can introduce in flies genomic sequences coming from other species and visualise their activity in the whole organism: the function of the DNA is translated into images that we can compare to identify which changes have occurred during evolution.

We analysed in fruit flies the evolutionary path followed by a gene family that we have selected as a study case. The multiple members of this gene family appeared after different events of gene duplication. After each event, the two new copies have diverged and developed new features. We have shown that this functional divergence occurs in general in a asymmetric way, with one copy assuming the roles of the ancestral gene and the other copy being free to assume new functions and rapidly diverge. We are now analysing the molecular changes that have determined this divergence process at the level of the DNA sequence of the two copies.

The structure and, consequently, the function of the genomes of all living beings is the result of contingent processes whose deep logic remains largely unknown. The most important aspect of the basic research we conduct is to develop experimental systems where to dissect the underlying mechanisms that shape genomes over time. Our work is aimed at understanding the biological codes that allow translating the information contained in the lineal sequence of DNA into structures, dimensions and biological functions.

We have already published in a scientific journal some of our latest discoveries ! This publication is available to all the public by clicking the following link :
mbe.oxfordjournals.org/content/32/7/1730.long

Enjoy your reading !

The profusion of gene paralogues (gene families) that are observed in all 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 is it permitted to accumulate formerly forbidden mutations and emerge as a new gene with a hitherto unknown function” (Ohno, 1970). Thus, the question of how gene duplication and subsequent divergence contributes to genetic novelty and adaptation has become a hot topic in evolutionary studies. This is not only due to the role of gene duplications as a catalyser of genetic innovation, but also because the growing knowledge of gene networks and their intrinsic logic has revealed that many properties of these networks, such as redundancy, co-option and modularity must be rooted on ancient duplication events.

Not surprisingly, for more than 30 years the question of how gene duplication and divergence contribute to genetic novelty and adaptation has been intensely debated. However, while many theoretical developments have greatly enriched the discussion, few experimental approaches have played a prominent role in the debate.

We thus propose to develop a novel experimental contribution focusing on the analysis of a reduced set of gene duplicates originated during the evolution of the diptera lineage, with the double objective of characterising their roles, (i.e., their functional fates), and analysing the divergence of their promoter sequences, all in a highly amenable system for both genetic and cis-regulation analysis: the fly Drosophila melanogaster. For this, we have chosen to focus a novel family of Drosophila paralogues recently described by us, whose members code for different GPI-anchored proteins sharing a conserved extracellular motif called Three Finger Domain (TFD).

Preliminary work carried out by the two groups involved in the proposal has already allowed to first, characterise the evolutionary history of the different TFD paralogues within the diptera lineage and, second, to establish that their expression patterns have undergone considerable changes during paralogue divergence. Thus, this experimental set-up constitutes a promising system to study cis-regulatory evolution, allowing direct evaluation of processes such as degeneration/conservation and/or co-option of specific regulatory modules. In parallel and using the large arsenal of genetic and technical resources available in Drosophila, we will also perform a functional analysis of the different TFD paralogues in order to establish their cellular role(s) during development.

This particular combination of structural (sequence analysis) and functional (gene expression/mutant analysis) studies will serve as a platform for inferring on the evolutionary paths undertaken by each gene duplicate, namely their neo- and/or subfunctionalization. In addition, we expect that the data set stemming from this project will be suitable to approach the nature and genesis of some of the properties of gene regulation and structure, such as modularity and its internal logic, enhancer sharing and co-option.