Obituary: Walter Fitch and the orthology paradigm

Walter M. Fitch, a towering giant of molecular evolution, passed away on 10 March 2011. His pivotal contributions to the field are manifold, diverse and profound. He developed some of the first algorithms and practical methods for phylogenetic tree construction; pioneered statistical approaches in sequence comparison and phylogenetic analysis; introduced the covarion approach in the study of gene evolution, a simple but powerful concept the full potential of which is not yet realized; and in the final years of his long and enormously productive career, laid the foundation of viral phylogenetics that has become essential for the most practical purpose of predicting the dominant influenza strain in the next epidemics. Fitch’s many fundamental achievements have been succinctly but clearly outlined in a recent Science Retrospective [1]. For the special issue of Briefings in Bioinformatics on orthology and orthologs, it seems most appropriate to focus on a single paper of Fitch in which he introduced the concepts and definitions of orthology and paralogy. Appearing in 1970 in a well-respected but relatively low key journal Systematic Zoology, under the unassuming (at least, at the time) title ‘Distinguishing homologous from analogous proteins’ [2], this paper hardly attracted much attention immediately upon its publication and was quite poorly cited over the next 25 years. This has changed when comparison of gene sets from completely sequenced genomes became the core of comparative and evolutionary genomics (Figure 1). All of a sudden, it became apparent that the straightforward classification of homologs introduced by Fitch in that article was absolutely essential for genomics to make any sense of the pouring genomes, so the citations have been accumulating at a good pace ever since (Figure 1). I would go as far as to submit that Fitch’s paper is the single most important conceptual cornerstone of modern genomics. Indeed, distinguishing orthologs from paralogs is critical for at least three key tasks [3]: