Functional and evolutionary implications of gene orthology

• Published in: Nature reviews. Genetics Vol. 14; no. 5; pp. 360 - 366
• Main Authors: Gabaldón, Toni, Koonin, Eugene V.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2013; Nature Publishing Group
• Subjects: 48; Agriculture; Animal Genetics and Genomics; Animals; Biomedicine; Cancer Research; Comparative analysis; Evolution, Molecular; Evolutionary biology; Gene Function; Genomics; Genomics - methods; Human Genetics; Humans; Models, Animal; Models, Genetic; opinion-2; Phenotype; Phylogeny; Sequence Analysis; United States
• ISSN: 1471-0056; 1471-0064
• DOI: 10.1038/nrg3456

The concepts of orthology and paralogy are fundamental to comparative genomics and are also frequently used for the functional annotation of uncharacterized genes. However, assumptions regarding function have recently been challenged, and the implications of assigning genes as orthologues or paralogues are far from straightforward. Orthologues and paralogues are types of homologous genes that are related by speciation or duplication, respectively. Orthologous genes are generally assumed to retain equivalent functions in different organisms and to share other key properties. Several recent comparative genomic studies have focused on testing these expectations. Here we discuss the complexity of the evolution of gene–phenotype relationships and assess the validity of the key implications of orthology and paralogy relationships as general statistical trends and guiding principles.