A genomic predictor of lifespan in vertebrates

Abstract

Biological ageing and its mechanistic underpinnings are of immense biomedical and ecological significance. Ageing involves the decline of diverse biological functions and places a limit on a species' maximum lifespan. Ageing is associated with epigenetic changes involving DNA methylation. Furthermore, an analysis of mammals showed that the density of CpG sites in gene promoters, which are targets for DNA methylation, is correlated with lifespan. Using 252 whole genomes and databases of animal age and promotor sequences, we show a pattern across vertebrates. We also derive a predictive lifespan clock based on CpG density in a selected set of promoters. The lifespan clock accurately predicts maximum lifespan in vertebrates (R² = 0.76) from the density of CpG sites within only 42 selected promoters. Our lifespan clock provides a wholly new method for accurately estimating lifespan using genome sequences alone and enables estimation of this challenging parameter for both poorly understood and extinct species.

Figure 1

Lifespan Estimation from CpG density with lifespan loci. The correlation between the known and predicted lifespan in the (a) training and (b) testing data set. Colours denote the class of each species. The R² value and p-value are given above each plot.

Figure 2

Performance and characterisation of the lifespan loci. Box plots show the (a) Absolute error rate, (b) relative error rate of each species in the training and testing data sets. Each dot point overlayed on the box plots represent an individual species.

Figure 3

Weighting and correlation coefficients of the lifespan loci. (a) Weighting of each lifespan loci in order from most positive to negative in magnitude. (b) Pearson correlation compared to the weight of each lifespan loci.

Figure 4

Principle component analysis using the CpG density in the lifespan loci which shows the species separate based on their known lifespans. Species are coloured by increasing lifespan.