Chromosomes in the Light of Evolution

Chromosome rearrangements are a hallmark of genome evolution and essential for understanding the mechanisms of speciation and adaptation.  Determining the types and chronology of chromosome rearrangements over evolutionary time scales has been a difficult problem due primarily to the lack of high quality, chromosome-scale genome assemblies that are necessary for reliable reconstruction of ancestral genomes.  In addition, for genome-wide comparisons that require resolving large numbers of rearrangements of varying scale, determining ancestral chromosomal states is challenging both methodologically and computationally.  We recently developed a new computational tool for reconstructing ancestral chromosomes at high resolution, called DESCHRAMBLER, which uses syntenic fragments constructed from whole-genome comparisons of both high quality chromosome-scale and fragmented assemblies in a phylogenetic probabilistic framework.  We applied DESCHRAMBLER to sequenced genomes of 21 species that included representatives of 10 eutherian orders.  Seven ancestral genomes leading to human were reconstructed, including the ancestor of all placental mammals.  These reconstructions revealed a detailed history of chromosome rearrangements that occurred during ~105 million years of eutherian evolution.  Our results provide an evolutionary basis for comparison of the genome organization of all eutherians that will facilitate greater understanding of the role of chromosome rearrangements in adaptation, speciation, and the etiology of inherited and spontaneously occurring diseases.  With ongoing efforts to sequence vertebrate genomes from all classes, it will be possible to extend chromosome reconstructions deeper into evolutionary time.  Sequence-based reconstruction of ancestral chromosomes thus provides a new opportunity to bridge the gap between traditional cytogenetics and genomics by illuminating the origins of ancestral synteny and the timing of chromosome rearrangements during evolution.