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

Area of Science:

• Genomics
• Comparative Biology
• Evolutionary Biology

Background:

• Rodents exhibit diverse lifespans and cancer resistance, with mice being short-lived and cancer-susceptible, while mole-rats are long-lived and cancer-resistant.
• Understanding genetic differences in rodents can inform their use as biomedical models.

Purpose of the Study:

• To identify gene pathways with higher similarity between cancer-resistant mole-rats compared to cancer-susceptible mice.
• To explore the evolutionary divergence of these pathways in rodents and humans.

Main Methods:

• Comparative genomic analysis of mouse, mole-rat, and other rodent species genomes.
• Identification of enriched gene pathways, focusing on cell cycle control, stem cell pathways, and ubiquitin-dependent protein degradation.
• Analysis of non-synonymous to synonymous nucleotide substitution ratios (dN/dS) to infer evolutionary rates.

Main Results:

• Cell cycle control pathways, including external signal transduction and stem cell pathways, were prominent in genes more similar between mole-rats than between mice and mole-rats.
• Ubiquitin-dependent protein degradation emerged as a core network, though not exclusive to mole-rats.
• Muroid rodents (e.g., mice, rats) showed distinct genetic features compared to non-muroid rodents and humans, with accelerated evolution in specific pathways.

Conclusions:

• Muroid rodents may not be ideal models for human cell cycle research due to significant genetic divergence in relevant pathways.
• The guinea pig is proposed as a more suitable rodent model for biomedical research involving cell cycle processes.
• Genomic comparisons highlight specific pathways where rodent and human genetic makeup differs, impacting model organism selection.