On the correlation between composition and site-specific evolutionary rate: implications for phylogenetic inference.

Model-based phylogenetic reconstruction methods traditionally assume homogeneity of nucleotide frequencies among sequence sites and lineages. Yet, heterogeneity in base composition is a characteristic shared by most biological sequences. Compositional variation in time, reflected in the compositional biases among contemporary sequences, has already been extensively studied, and its detrimental effects on phylogenetic estimates are known. However, fewer studies have focused on the effects of spatial compositional heterogeneity within genes. We show here that different sites in an alignment do not always share a unique compositional pattern, and we provide examples where nucleotide frequency trends are correlated with the site-specific rate of evolution in RNA genes. Spatial compositional heterogeneity is shown to affect the estimation of evolutionary parameters. With standard phylogenetic methods, estimates of equilibrium frequencies are found to be biased towards the composition observed at fast-evolving sites. Conversely, the ancestral composition estimates of some time-heterogeneous but spatially homogeneous methods are found to be biased towards frequencies observed at invariant and slow-evolving sites. The latter finding challenges the result of a previous study arguing against a hyperthermophilic last universal ancestor from the low apparent G + C content of its rRNA sequences. We propose a new model to account for compositional variation across sites. A Gaussian process prior is used to allow for a smooth change in composition with evolutionary rate. The model has been implemented in the phylogenetic inference software PHASE, and Bayesian methods can be used to obtain the model parameters. The results suggest that this model can accurately capture the observed trends in present-day RNA sequences.