Leveraging computational genomics to understand the molecular basis of metal homeostasis

Summary Genome‐based data is helping to reveal the diverse strategies plants and algae use to maintain metal homeostasis. In addition to acquisition, distribution and storage of metals, acclimating to feast or famine can involve a wealth of genes that we are just now starting to understand. The fast‐paced acquisition of genome‐based data, however, is far outpacing our ability to experimentally characterize protein function. Computational genomic approaches are needed to fill the gap between what is known and unknown. To avoid misconstruing bioinformatically derived data, which is the root cause of the inaccurate functional annotations that plague databases, functional inferences from diverse sources and contextualization of that evidence with a robust understanding of protein family evolution is needed. Phylogenomic‐ and comparative‐genomic‐based studies can aid in the interpretation of experimental data or provide a spark for the discovery of a new function. These analyses not only lead to novel insight into a target protein’s function but can generate thought‐provoking insights across protein families.