Ortholog

Orthologs are genes in different species that originated from a single gene in the last common ancestor of those species through a speciation event. They typically retain equivalent functions across species, but functional divergence can occur. Orthology is contrasted with paralogy, where genes are related by duplication within a genome, and xenology, where homology arises from horizontal gene transfer. The term emphasizes a genealogical relationship across species rather than a property of a single gene.

The identification of orthologs relies on phylogenetic analyses that reconcile gene trees with species trees to distinguish speciation from gene duplication events. Practical methods also use sequence similarity and synteny, such as reciprocal best hits and graph-based clustering. Several databases and tools provide orthology predictions, including OrthoMCL, eggNOG, OrthoDB, Ensembl Compara, and others. The concept is used with varying confidence depending on data quality and lineage history.

Orthology yields several relationship types. There are 1-to-1 orthologs (one gene per species), many-to-many orthologs after lineage-specific duplications, and co-orthologs when ancestral genes duplicated before species split. While 1-to-1 orthologs are often the most reliable for inferring conserved function and for functional annotation transfer, orthologous genes can diverge functionally over time.

Applications and limitations: Orthology is central to comparative genomics, enabling transfer of functional information and reconstruction of evolutionary histories. However, gene loss, duplication, rapid evolution, domain shuffling, or incomplete lineage sorting can complicate inference, leading to uncertainty in predicted relationships. Results are typically supported by multiple methods and species sampling.