From owner-celegans@net.bio.net Fri Jun 21 23:00:00 1996 Path: biosci!ACF2.NYU.EDU!fitch From: fitch@ACF2.NYU.EDU (David H. A. Fitch) Newsgroups: bionet.celegans Subject: Re: homologs, paralogs, orthologs Date: 22 Jun 1996 12:25:30 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 69 Sender: daemon@net.bio.net Distribution: world Message-ID: <9606221920.AA13100@acf2.NYU.EDU> NNTP-Posting-Host: net.bio.net Oliver Hobert writes-- >Hey folks - Can anybody supply me with an explanation what "homologs", >"paralogs" and "orthologs" mean in terms of gene sequence similarity, i.e. >when are two similar genes called homologs, paralogs or orthologs. >Thanks ! >Oliver It's easy...at least theoretically--someone said that "homology, whatever it means, is the most important concept in biology". Homologous features (the official word is "character")--whether they be genes, mechanisms or morphologies--share an evolutionary history. That is, homologs share a character, from which they were derived, in an ancestor. The way the character looks (its "state") is "primitive" if it looks like the ancestral character, and "derived" if it has changed from the ancestral state. Orthologs and paralogs are both homologs, but have more specific meanings (i.e., are subsets of "homolog")--both paralogs and orthologs are characters that share an evolutionary history. Orthologs have diverged because of a speciation event (e.g., when a gene in one species, like Antp in Drosophila, diverges from the same gene in another species, like mab-5 in C. elegans). Paralogs have diverged because of a gene duplication event (e.g., mab-5 and lin-39 are probably paralogs because they probably arose from a gene duplication event in an ancient ancestor). The story can get much more complicated. For example, the gamma-globin genes in the Anthropoidea duplicated before platyrrhine primates (New World monkeys) diverged from the lineage to catarrhines (Old World monkeys, apes and humans). That would make gamma-1-globin (G-gamma in the older nomenclature) and gamma-2-globin (A-gamma) paralogous. And gamma-1 in humans is orthologous to gamma-1 in chimpanzees. But intergenic conversions have occurred between parts of the duplicated genes in all of the lineages, greatly confusing these distinctions. For example, although the 3' noncoding regions retain evidence of independent evolution following the duplication and then the various speciation events, the 5' regulatory region and exon 1 of gamma-2 have been converted by gamma-1 in every lineage. Over these particular regions, the sequence of gamma-1 in humans is not really orthologous to the sequence of gamma-2 in chimpanzees because the gene conversion events occurred after the divergence of these two species. To make matters even worse, people have developed even more names for various types of homologous relationships. For example, xenologous genes are those shared by gene transfer between species, such as through a retroviral vector. For example, P elements appear to have recently invaded D. melanogaster by cross-species transfer from D. willistoni (there is only one base pair difference in the P elements of these two species, but the species are much more divergent). There is a very readable, inexpensive little book about these and many other aspects of molecular evolution: Li and Graur, 1991, Fundamentals of Molecular Evolution (pub. by Sinauer Associates, Sunderland, MA). Hope this helps. Dave ~~~~~~~~~~~~~~~~~~~~~~~~~~~~ ~ ~ - - ~ David Fitch ~ \ / / / ~ Department of Biology ~ \ / / ~ New York University ~ [] / / ~ Main Building, Room 1009 ~ \ / / ~ New York, NY 10003 ~ \ / ~ 212-998-8254 ~ \ / ~ fax 212-995-4015 ~ / ~ fitch@acf2.nyu.edu ~ / ~~~~~~~~~~~~~~~~~~~~~~~~~~~~ .