The role and implications of gene duplication events on vertebrate genome evolution

The annotated genome sequences of the vertebrates human, mouse, rat, chicken, frog, zebrafish, and Tetraodon were the ideal starting point for an analysis of whole-genome duplications. The research presented in this thesis helps to answer three key questions: Did whole-genome duplications occur during vertebrate evolution? If so, what was their role? How do duplicated genes evolve? A first step was to search for genes that originated in these large–scale duplication events, count them and compare them with genes that arose via other, small–scale, duplication events. We applied a method based on phylogenetic trees to identify the duplicated genes and determine their origin. Phylogenetic trees are an attempt to learn more about the evolutionary relationships between genes and are thus a means to detect gene duplicates in a genome. Chapter 2 goes into the detail of the problems we faced when we implemented this technique for a large dataset, and explains different methodologies for the identification of duplication events in the trees. The next chapter (3) presents the results of the quantitative and qualitative analysis of this dataset of more than 10,000 trees. We studied gene loss and retention after duplication events, and identified to what processes these duplicated genes mostly contributed. Chapter 4 describes the identification of some example cases where subfunctionalization, a process that spreads the function of the original genes to the duplicate copies, may have taken place after duplication in the genomes of zebrafish and Tetraodon. Chapter 5 places these findings in the perspective of other published research analyses, and explains other recently discovered features of whole–genome duplications. Briefly, (i) we built a high–throughput pipeline for the automatic construction and reconcili- ation of phylogenetic trees; (ii) we found additional evidence for three whole–genome duplications in vertebrate evolution; (iii) we showed that retained duplicates from large–scale and small–scale duplications have different functions; (iv) we discovered that very old duplicates can still get lost after many millions of years of retention; (v) we studied how subfunctionalization of gene regulation after whole–genome dupli- cation can be detected via in vitro studies