Accelerated pathway evolution in mouse-like rodents involves cell cycle control

Abstract

Rodents include both the cancer-susceptible short-lived mouse and the two unrelated cancer-resistant long-lived mole-rats. In this work, their genomes were analyzed with the goal to reveal pathways enriched in genes, which are more similar between the mole-rats than between the mouse and the naked mole-rat. The pathways related to cell cycle control were prominent. They include external signal transduction and all cell cycle stages. There are several stem cell pathways among them. The other enriched pathways involve ubiquitin-dependent protein degradation, immunity, mRNA splicing, and apoptosis. The ubiquitin-dependent protein degradation is a core of network of enriched pathways. However, this phenomenon is not specific for the mouse and the mole-rats. The other muroid species show features similar to the mouse, whereas the non-muroid rodents and the human show features similar to the mole-rats. The higher ratio of non-synonymous to synonymous nucleotide substitutions (dN/dS) indicates the accelerated evolution of revealed pathways in the muroid rodents (except the blind mole-rat). Paradoxically, the dN/dS averaged over the whole genome is lower in the muroids, i.e., the purifying selection is generally stronger in them. In practical sense, these data suggest caveat for using muroid rodents (mouse, rat, and hamsters) as biomedical models of human conditions involving cell cycle and show the network of pathways where muroid genes are most different (compared with non-muroid) from human genes. The guinea pig is emphasized as a more suitable rodent model for biomedical research involving cell cycle.

Molecular Genetic Analysis of Human Endometrial Mesenchymal Stem Cells That Survived Sublethal Heat Shock

“…The biological processes and molecular pathways enriched in differentially expressed genes were found similar to previous works [ 30 , 31 ]. The biological processes were taken from GO database [ 32 ].…”

Somatic polyploidy is associated with the upregulation of c-MYC interacting genes and EMT-like signature

“…We tested the genes from all three data sets (Supplementary Tables S4–S6) with higher and lower expression in polyploid vs diploid tissues and cells, respectively, for enrichment of Gene Ontology (GO) categories and molecular pathways with regard to all human-mouse orthologous genes (13965 genes) and simultaneously with regard to all known orthologous c-MYC – interacting genes (3734 genes). The enriched GO categories and molecular pathways were found using the hypergeometric distribution of probability (implemented in R package) as in the previous work [115, 116]. GO categories were taken from GO database [117].…”

Unraveling the message: insights into comparative genomics of the naked mole-rat

“…On the other hand, multiple pathways associated with proteostasis, genomic stability, and cell cycling are more similar between the naked mole-rat, other nonmuroid rodents (including above-ground dwelling rodents, i.e., guinea pigs, chinchillas, squirrels, and jerboas) and humans than among laboratory mice and rats and these species. These pathways likely underwent accelerated evolutionary change in both rats and mice and much slower divergence in the nonmuroid rodents and humans (Vinogradov 2015 ). This divergence of the Muridae (rats and mice) from the ancestral lineages is thought to reflect a relaxation in purifying selection of these pathways essential for both genomic and proteomic stability (Vinogradov 2015 ).…”

“…These pathways likely underwent accelerated evolutionary change in both rats and mice and much slower divergence in the nonmuroid rodents and humans (Vinogradov 2015 ). This divergence of the Muridae (rats and mice) from the ancestral lineages is thought to reflect a relaxation in purifying selection of these pathways essential for both genomic and proteomic stability (Vinogradov 2015 ). This may explain the greater propensity for cancer and a shorter than expected lifespan predicted on the basis of their body size for muroid rodents (Hulbert et al 2007 ).…”