Genome Rearrangements: Structural Inference and Functional Consequences

As genomes evolve over hundreds of millions years, the chromosomes become rearranged, with segments of some chromosomes inverted, while other chromosomes reciprocally exchange chunks from their ends. These rearrangements lead to the scrambling of the elements of one genome with respect to another descended from a common ancestor. Multidisciplinary work undertakes to mathematically model these processes and to develop statistical analyses and mathematical algorithms to understand the scrambling in the chromosomes of two or more related genomes. A major focus is the reconstruction of the gene order of the ancestral genomes. There has been a trend in increasing the phylogenetic scope of genome sequencing without finishing the sequence for each genome. With less interest in completing the sequence, there is an increasing number of genomes being published in scaffold or even contig form. Rearrangement algorithms, including gene order-based phylogenetic tools, require whole genome data on gene order or syntenic block order. Then, for gene order-based comparisons or phylogeny, how can we use rearrangement algorithms to handle genomes available in contig or scaffold form only? For contig data, we develop a model for the behaviour of the genomic distance as a function of evolutionary time, and discuss how to invert this function in order to infer elapsed time. We show how to correct for the effect of chromosomal fragmentation in sets of contigs. We apply our methods to data originating mostly in the 12-genome Drosophila project [15]. We compare ten Drosophila genomes with two other dipteran genomes and two outgroup insect genomes. For scaffolds, our method involves optimally filling in genes missing in the scaffolds, and using the augmented scaffolds directly in the rearrangement algorithms as if they were chromosomes, while making a number of corrections, e.g., we correct for the number of extra fusion/fission operations required to make scaffolds comparable to full assemblies. We model the relationship between scaffold density and genomic distance, and estimate the parameters of this model while comparing the angiosperms genomes Ricinus communis and Vitis vinifera. A separate question arises of what the biological consequences of breakpoint creation are, rather than just their structural aspects. The question I will ask is whether proximity to the site of a breakpoint event changes the activity of a gene. I propose to investigate this by comparing the distribution of distances to the nearest breakpoint of genes that change expression in human versus the distribution of genes that do not change expression in human, compared to other primate species (e.g. macaque or chimpanzee). Keywords: chromosome rearrangement, comparative genomics, phylogenomics, phylogenetic tree, inversion, reciprocal translocation, transposition, DCJ, breakpoint, gene expression