The Genomic Geography and Evolution of Clusters of Tandemly Duplicated Genes in the Human and Mammal Genomes

Clusters of duplicated genes (CTDGs) are nearly ubiquitous in life's genomes, and are associated with several well-known gene families, such as olfactory receptors, zinc fingers, and immunity-related genes, as well as with several highly variable traits, including olfaction, body plan architecture, and pathogen resistance. However, these observations are usually anecdotal, restricted to specific cases, and lacking evolutionary context. In this study, we use a robust statistical approach to characterize the CTDG repertoire and analyze the distribution of CTDGs across 18 mammal genomes, including human. We found that, on average, 18% of the genes in each species are parts of CTDGs. Although genes in CTDGs are enriched for several biological processes, these tend to be involved in the interactions between the organism and its environment. We further found that mammalian CTDGs are not uniformly distributed across chromosomes and that orthologs of the human chromosome 19 are among the most clustered chromosomes in nearly all mammalian genomes analyzed. We also found evidence that the human chromosome 19 was formed by a fusion event that occurred before the diversification of the rodent and primate lineages and maintained its high density of CTDGs during its subsequent evolution. Finally, using chromosome-level alignments across mammalian genomes, we show how the syntenic regions of the human chromosome 19 have been shrinking, increasing their gene density and possibly increasing the compactness of its CTDGs. These results suggest that CTDGs are a major feature of mammalian genomes and provide novel insights into the origin and evolution of regions with unusually high densities of CTDGs.