Abstract
Mammals have developed different kinds of renal structures during evolution, yet the origin of the renal structural phenotypes and the molecular mechanisms underlying their adaptive evolution remains unclear. Here, we reconstructed the ancestral state of the renal structures across mammals and found that the unilobar kidney was the ancestral character in mammals. The subsequent correlation analyses between renal phenotypes and life history traits revealed that species with a larger body or in aquatic habitats tend to have evolved discrete multirenculate kidneys. To explore the molecular convergent mechanisms among mammals with this most distinct renal structure, the discrete multirenculate kidney, we used 45 genes related to duplex/multiplex kidney diseases to compare the evolutions of species with discrete multirenculate kidneys and with other renal phenotypes. Twelve rapidly evolving genes that were functionally enriched in cilium assembly and centrosome were identified in species with discrete multirenculate kidneys, suggesting that these genes played key roles in the evolution of discrete multirenculate kidneys. In addition, positive selection was detected in six crucial genes which are mainly involved in epithelial tube morphogenesis and regulation of neurogenesis. Finally, 12 convergent amino acid substitutions, six of which are in crucial domain of proteins, were shared by two or more lineages with discrete multirenculate kidneys. These findings could provide some novel insights into the origin and evolution of renal structures across mammals and the pathogenesis of renal diseases in humans.