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homologs, paralogs, orthologs

David H. A. Fitch fitch at ACF2.NYU.EDU
Sat Jun 22 14:25:30 EST 1996

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 !

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

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

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.

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