Somatic mutation rates scale with lifespan across mammals

Area of Science:

• Evolutionary biology
• Genetics
• Comparative genomics

Background:

• Somatic mutation rates and patterns in normal tissues are poorly understood across species.
• Comparative analyses are crucial for understanding mutagenesis evolution and its role in cancer and aging.

Purpose of the Study:

• To investigate the landscape of somatic mutations across 16 mammalian species.
• To explore the relationship between somatic mutation rates, lifespan, and other life-history traits.

Main Methods:

• Whole-genome sequencing of 208 intestinal crypts from 56 individuals across 16 mammalian species.
• Analysis of mutational signatures and mutation rates per year.

Main Results:

• Somatic mutagenesis is dominated by endogenous processes (e.g., 5-methylcytosine deamination, oxidative damage) in all species.
• Mutational signatures are conserved across mammals but their relative contributions vary.
• Somatic mutation rate per year shows a strong inverse correlation with species lifespan.
• Somatic mutation burden at the end of lifespan is relatively consistent across species despite wide variations in lifespan and body mass.

Conclusions:

• Mammalian species share common endogenous mutational processes.
• Somatic mutation rates appear evolutionarily constrained.
• Constrained somatic mutation rates may be a contributing factor to aging.