homolog vs paralog?

Edward Braun ebraun at UNM.EDU
Mon Feb 10 13:29:35 EST 1997


HOMOLOG is a general term, simply used to indicate genes or proteins (or
other structures) that are meaningfully related by evolution.  Homologous
proteins may be either ORTHOLOGS or PARALOGS.

For ORTHOLOGS (ortho=exact) the homology is the result of speciation so
that the history of the gene reflects the history of the species (in other
words, this is the case where you are looking at the same exact gene in
different organisms).  Many people use homolog as a synonym for ortholog,
but this is not correct.

On the other hand, for PARALOGS (para=in parallel) the homology is the
result of a gene duplication and the history of the genes does not reflect
the history of the species (in this case you are looking at similar
proteins, potentially within the same organism).

Paralogy does not have any functional connotation - for example, EF-1alpha
and EF-2 act differently in protein synthesis but they are paralogs that
resulted from a gene duplication that was present in the last common
ancestor of all organisms (see Baldauf et al. 1996 PNAS vol. 93: 7749-7754
and refs. therein) although some paralogs do have overlapping functions
(e.g. the 2 EF-1alpha genes in yeast, etc.)  Obviously, the duplication may
be ancient (the EFs) or relatively recent.

Some of the folks at TIGR have used the term ISOLOG (see, for example, the
THC paper in the supplement to Nature, or Fields & Adams, 1994 BBRC vol.
198: 288-291) to indicate homologs where orthology or paralogy is not
clear.  Obviously, this is somewhat superfluous with the term homolog, but
they are probably trying to avoid the confusion over the term homolog that
I mentioned above.

An excellent recent discussion of the terms can be found in:

  Gogarten, J.P. (1994)  What is the most conserved group of proteins?
  Homology-orthology, paralogy, xenology, and the fusion of independent
  lineages.  Journal of Molecular Evolution vol. 39:541-543.

and the terms ortholog and paralog were discussed in:

  Fitch, W.M. (1970)  Distinguishing homologous from analogous proteins.
  Systematic Zoology vol. 19:99-113

>>To: yeast at net.bio.net
>>From: neigeborn at ocelot.rutgers.edu ("Neigeborn, Lenore")
>>Subject: homolog vs paralog?
>>Date: 10 Feb 1997 08:48:37 -0800
>>Sender: daemon at net.bio.net
>>NNTP-Posting-Host: net.bio.net
>>Can someone clarify for me the distinction in usage between the terms homolog
>>and paralog?  Exactly what is a paralog and when is it appropriate to use the
>>term (in lieu of homolog, when all one knows is sequence similarity)?
>>After the last big yeast meeting, I came home with the idea that a paralog
>>was a
>>"homolog within the same species" based on sequence, not necessarily
>>functionality.  Lately, I'm beginning to doubt that this is correct.

- Edward Braun,  UNM Biology.

Edward Braun                             TEL: currently moving!
Castetter Hall                           FAX: (505) 277-0304
Department of Biology                    EMAIL: ebraun at unm.edu
University of New Mexico
Albuquerque, NM 87131

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