Proteins and Pathways Associated with Long-Lived Mammals
Although much progress has been made in dissecting the genetics of ageing in model organisms, the genetic basis of species differences in longevity (e.g., why does a mouse cannot live more than 5 years yet humans can live over 100?) remains a major puzzle. The genome sequencing of a large number of species provides new opportunities to gain insights into adaptive genetic changes associated with the evolution of lifespan and this is a rapidly expanding field. We developed a method to identify candidate genes involved in species differences in ageing based on detecting proteins with accelerated evolution in multiple lineages where longevity increased. By applying our method to lineages leading to over 30 mammals of varying lifespans, we discovered both single proteins (~100) and functional categories associated with the evolution of longevity. These include proteins involved in DNA damage response and the proteasome-ubiquitin pathway and thus provide evidence that at least some repair systems were selected for, and arguably optimized, in long-lived species. We also discovered that proteins involved in lipid metabolism and cholesterol catabolism were more prone to have such longevity-associated signature when compared to a random model. This page provides the supplementary material previously described in:
Li Y, de Magalhaes JP (2013) Accelerated protein evolution analysis reveals genes and pathways associated with the evolution of mammalian longevity. Age (Dordr) 35:301-314.
- mammalian_supplement.zip, zipped file with the full results of candidate longevity-selected genes and supplementary methods.