Orthologs

Orthologs are genes in different species that originated from a single gene in the last common ancestor through speciation. After speciation, the gene copies may diverge in sequence and sometimes in function, but they often retain equivalent roles in their respective organisms. Orthologs are a fundamental concept in comparative genomics and are frequently used to infer gene function across species. For example, a human gene and its mouse ortholog may perform related biological roles.

Orthology is distinct from paralogs, which arise by gene duplication within the same lineage and can evolve new or specialized functions. Xenologs refer to genes acquired by horizontal gene transfer between species. The study of orthologs is central to functional annotation transfer: researchers use orthologous relationships to predict the function of genes in model organisms and to compare pathways and phenotypes across species. However, functional conservation is not guaranteed, particularly after duplications or lineage-specific innovations.

Identifying orthologs involves phylogenetic analysis of gene families and reconciliation with species trees, sometimes supported by synteny or gene neighborhood information. Methods range from tree-based reconciliation to clustering and network approaches. Relationships can be one-to-one, one-to-many, or many-to-many, reflecting duplication events in the evolutionary history of the species involved.

Orthology has broad applications in evolution, comparative genomics, and biomedical research, enabling cross-species annotation of gene function, the study of conserved pathways, and the selection of appropriate model organisms for studying human biology and disease.