Gemmell, P. | bioRxiv Science

bioRxiv2024

Linking phenotypic and genotypic variation: a relaxed phylogenetic approach using the probabilistic programming language Stan

PhyloG2P methods link genotype and phenotype by integrating evidence from across a phylogeny. I introduce a Bayesian approach to jointly modelling a continuous trait and a multiple sequence alignment, given a background tree and substitution rate matrix. The aim is to ask whether faster sequence evolution is linked to faster phenotypic evolution. Per-branch substitution rate multipliers (for the alignment) are linked to per-branch variance rates of a Brownian diffusion process (for the trait) via the flexible logistic function. The Brownian diffusion process can evolve on the same tree used to describe the alignment, or on a second tree, for example a tree with branch lengths in units of time. Simulation studies suggest the model can be well estimated using relatively short alignments and reasonably sized trees. An application of the model in both its one-tree and two-tree variants is provided as an example. Notably, the method is implemented concisely using the general-purpose probabilistic programming language Stan.

bioinformatics↗

bioRxiv2023

A phylogenetic method linking nucleotide substitution rates to rates of continuous trait evolution

Genomes contain conserved non-coding sequences that perform important biological functions, such as gene regulation. We present a phylogenetic method, PhyloAcc-C, that associates nucleotide substitution rates with changes in a continuous trait of interest. The method takes as input a multiple sequence alignment of conserved elements, continuous trait data observed in extant species, and a background phylogeny and substitution process. Gibbs sampling is used to assign rate categories (background, conserved, accelerated) to lineages and explore whether the assigned rate categories are associated with increases or decreases in the rate of trait evolution. We test our method using simulations and then illustrate its application using mammalian body size and lifespan data previously analyzed with respect to protein coding genes. Like other studies, we find processes such as tumor suppression, telomere maintenance, and p53 regulation to be related to changes in longevity and body size. In addition, we also find that skeletal genes, and developmental processes, such as sprouting angiogenesis, are relevant. The R/C++ software package implementing our method is available under an open source license from https://github.com/phyloacc/PhyloAcc-C.

bioinformatics↗