The Coordinated Roles of DNA Damage Repair, Genome Stability and Non-Adaptive Radiations in Vertebrate Evolution

A correlation between karyotype diversity and species richness was first observed in mammals in 1980 and subsequently confirmed after controlling for phylogenetic signal. The correlation was attributed to sub-microscopic factors, presumably operating at the level of the nucleus. The identities of these factors, however, remain unknown. Moreover, evidence demonstrating that they play any role in determining a relationship between karyotype diversity and species richness either in mammals or more generally in vertebrates is lacking. Species richness is commonly believed to be the result of diversifying selection occurring during adaptive radiation. Karyotypes, however, appear to evolve neutrally with selection acting primarily but not exclusively on genetic diversity. In 1991, Motoo Kimura proposed a molecular theory of non-adaptive radiation (NAR). Accordingly, genetic drift plays a significant role in speciation, albeit in parallel to and in conjunction with natural selection, suggesting that the nearly neutral evolution of karyotypes might participate in evolutionary dynamics during non-adaptive phases of adaptive radiations. The following will examine the contribution of DNA repair factors to the relationship between species richness and karyotype diversity and, by extension, to the large variation in species richness across the mammalian Tree of Life. Significance: As an integral part of the eukaryote DNA replication timing program (RT), DNA damage detection and repair systems (DDRs), including cell-cycle checkpoint systems and DNA double-strand break (DSB) repair pathways, organize the DNA synthetic phase (S phase) of the cell cycle and serve to coordinate genome duplication with mitosis and cell division. This review examines the role the DDR plays in sustaining and constraining mutation/substitution balance and the corresponding levels of genetic and genomic diversity on which natural selection operates. The efficiency and strength of the DDR, therefore, have important implications not only for genome stability but also for the evolution of genome architecture, karyotype diversity and, potentially, species richness. Many studies have been devoted to the role the DDR plays in cancer prevention and the evolution of body size and lifespan (K vs. r-strategists), but few studies have directly examined the role the DDR plays in speciation and adaptive radiations.