From Trees to Traits: A Review of Advances in PhyloG2P Methods and Future Directions.

Mapping genotypes to phenotypes is a fundamental goal in biology. Phylogenetic Genotype to Phenotype mapping methods are a relatively new set of tools that aim to identify genomic regions associated with trait variation between species. Here, we review recent developments in Phylogenetic Genotype to Phenotype mapping methods, focusing on three key areas: methods based on replicated substitutions at individual amino acid sites; methods detecting changes in evolutionary rates; and methods analyzing gene duplication and loss. We discuss how trait definition and measurement can impact these methods, as well as the genetic mechanisms that can give rise to trait variation between lineages. We examine the strengths and limitations of different approaches, highlighting the importance of explicit modeling of evolutionary processes. Finally, we outline promising future directions, including the integration of within-species variation, as well as epigenetic and environmental information. Since no single method is likely to identify all genomic regions of interest, we encourage users to apply a representative range of methods that are capable of detecting different types of associations. Overall, this review provides practitioners a roadmap for understanding and applying Phylogenetic Genotype to Phenotype mapping approaches.