Molecular evolution of Toll-like receptors in rodents

Toll-like receptors (TLRs), the key sensor molecules in vertebrates, trigger the innate immunity and prime the adaptive immune system. The TLR family of rodents, the largest order of mammals, typically contains 13 TLR genes. However, a clear picture of the evolution of the rodent TLR family has not yet emerged and the TLR evolutionary patterns are unclear in rodent clades. Here, we analyzed the natural variation and the evolutionary processes acting on the TLR family in rodents at both the interspecific and population levels. Our results showed that rodent TLRs were dominated by purifying selection, but a series of positively selected sites (PSSs) primarily located in the ligand-binding domain was also identified. The numbers of PSSs differed among TLRs, and nonviral-sensing TLRs had more PSSs than those in viral-sensing TLRs. Gene-conversion events were found between TLR1 and TLR6 in most rodent species. Population genetic analyses showed that TLR2, TLR8, and TLR12 were under positive selection in Rattus norvegicus and R. tanezumi, whereas positive selection also acted on TLR5 and TLR9 in the former species, as well as TLR1 and TLR7 in the latter species. Moreover, we found that the proportion of polymorphisms with potentially functional change was much lower in viral-sensing TLRs than in nonviral-sensing TLRs in both of these rat species. Our findings revealed the first thorough insight into the evolution of the rodent TLR genetic variability and provided important novel insights into the evolutionary history of TLRs over long and short timescales.