ortholog and paralog
duret at acnuc.univ-lyon1.fr
Wed Feb 12 04:06:01 EST 1997
In article <Pine.SOL.3.95.970211174614.5421A-100000 at lovelace.infobiogen.fr>, Pierre Pontarotti <pontaro at lovelace.infobiogen.fr> writes:
>I have a semantic question can we say that a gene family in one specie is
>ortholog to the same multigenic family in an other specie
Two genes are said to be orthologous if they diverged after a
speciation event, whereas they are said to be paralogous if
they diverged after a duplication event. If I'm not wrong, the original
quotation is by Fitch (1970 Systematic Zoology 19:99-113):
"Where the homology is the result of gene duplication so that
both copies have descended side by side during the history of
an organism, (for example, alpha and beta hemoglobin) the genes
should be called paralogous (para = in parallel). Where the
homology is the result of speciation so that the history of the
gene reflects the history of the species (for example alpha
hemoglobin in man and mouse) the genes should be called orthologous
(ortho = exact)."
This is also well explained in books such as "Fundamentals of
molecular evolution" by Li & Graur 1991 Ed. Sinauer Associates, Inc.,
Sunderland, Mass., USA.
What terms should be used where there is a speciation event, followed
by duplication events in both lineages ? For example:
| |_________ Rat_gene_2
| _____________ Mouse_gene_1
Mouse |_____________ Mouse_gene_2
where () indicates speciation and X indicates gene duplication
According to Fitch's definition, Mouse_gene_1 and Mouse_gene_2 are
paralogous, as are Rat_gene_1 and Rat_gene_2.
But Rat_gene_1 is orthologous both to Mouse_gene_1 and to Mouse_gene_2,
since Rat_gene_1 and the ancestor of the 2 mouse genes diverged
after a speciation event. Hence we have:
Rat_gene_1 is orthologous to Mouse_gene_1 and to Mouse_gene_2
Rat_gene_2 is orthologous to Mouse_gene_1 and to Mouse_gene_2
Mouse_gene_1 is orthologous to Rat_gene_1 and to Rat_gene_2
Mouse_gene_2 is orthologous to Rat_gene_1 and to Rat_gene_2
Hence, it seems acceptable to say the the mouse gene family
(that includes Mouse_gene_1 and Mouse_gene_2) is orthologous
to the rat gene family (Rat_gene_1 and Rat_gene_2).
Note that many molecular biologists confuse "orthology" and
"functional equivalence". For example Koonin et al. (Trends
in Genetics 1996 12:334-336) wrote:
"By definition, orthologs are genes that are related by vertical
descent from a common ancestor and encode proteins with the same
function in different species. By contrast, paralogs are homologous
genes that have evolved by duplication and code for protein
with similar, but not identical functions."
Does Rat_gene_1 have the same function as Mouse_gene_1 or as
Mouse_gene_2 ? Indeed, THE PHYLOGENETIC ANALYSIS ALLOWS
ONE TO DETERMINE ORTHOLOGY RELATIONSHIPS BUT NOT FUNCTIONAL
In fact, whereas it is likely that two orthologs have similar
function, these functions are not necessarily "identical".
For example, in pufferfish, the alpha-actin isoform that is
expressed in skeletal muscle is orthologous to mammalian
alpha-cardiac actin and not to mammalian alpha-skeletal actin.
Thus, in this case, orthologous genes have acquired different
tissue-specificity in mammals and pufferfish. A contrario, the
pufferfish alpha-actin isoforms expressed in cardiac muscle
are paralogous to mammalian alpha-cardiac actins.
It seems to me that it is important not to confuse "orthology"
with "functional equivalence". Now that the importance of
comparative genomics is well recognized it is essential to
avoid misunderstandings !
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