Computational comparative genomics: inferring and analyzing ancestral genomes architectures

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The central problem that I will address is the inference of ancestral genome architectures. Due to DNA decay, most ancestral genomes cannot be obtained directly by sequencing (from fossils for example). Instead, they must be inferred through the comparison of the genomes of their extant descendants, an approach which was pioneered by cytogeneticists. More recently, following the sequencing and assembly of a growing number of eukaryotic genomes, this approach was investigated by computational biologists. This resulted in a lively methodological debate between both communities, which has now been more or less settled, at least in the case of mammalian genomes. The next bottleneck, for vertebrate genomes, is now to infer the genome structure of the amniote ancestor, and of older ancestors, which is the starting point of my research program. The main motivation for inferring ancient eukaryote ancestors is to push further our current understanding of the evolutionary forces that shape today's genomes. The proposed research program has two main goals: 1. To develop methodologies and efficient algorithms for inferring ancestral genome architectures, composed of Contiguous Ancestral Regions (CARs) and Ancestral Link age Groups (ALGs), both at a high resolution (on the order of a few hundreds kbs). The originality of my approach will be to rigorously combine principles and concepts from different problems: physical mapping, comparative genome assembly, genome rearrangements methods, synteny conservation models, phylogenomics. 2. To infer ancestral genomes in important groups such as vertebrate genomes and angiosperms, and to combine these ancestral genomes with extant genomes to address important questions related to the evolution of eukaryotic genomes. I will investigate problems such as the inference reliable genome rearrangement events, mapping of breakpoint regions and regulatory regions on ancestral chromosomes to evaluate the link between gene regulation and synteny breakage, and measuring the correlation between GC content and chromosomes size.