[BiO BB] orthologs vs in-paralogs

Dan Bolser dmb at mrc-dunn.cam.ac.uk
Fri Sep 5 08:15:18 EDT 2003

Boris Steipe said:
> Phil Luo wrote:
>> Dear all,
>> As we know ,there are two kinds of homolog, ortholog and paralog. Genes in two
>> species that have directly evolved from a single gene in the last common
>> ancestor are called orthologs. A set of homologous genes that have diverged from
>> each other as a consequence of genetic duplication are called paralogs. Sometime
>> those paralogs which arose from a duplication after the speciation event are
>> called in-paralogs.
>> My question is how to distinguish the in-paralogs from orthologs.
> Paralogs have different functions. biochemistry, not bioinformatics.

How about redundant functions?

>> Which one is
>> supposed to be more similar, in-paralogs or orthologs?
> To the degree that the evolutionary rates remain the same, the difference will be
> proportional to the time of separation from the common ancestor. For orthologs
> this is the speciation event. For in-paralogs this is the duplication event.
> Accordingly you would expect a situation in which pradoxically a protein and it's
> paralog would be more similar than that protein and its ortholog in another
> species.

I think this should be common in 'lineage specific gene expansion' re: Eugene Koonin.

> That need not be universally true however, since the divergence of an in-paralog
> (post-duplication) may occur under reduced selective pressure since the original
> protein still fulfills its function. Thus the evolutionary rates need not be the
> same.

This has been argued to be one of the major driving forces for evolution (gene
function innovation). I am sorry but I can't remember the reference for this

> Accordingly: if you find paradoxical similarities as above, your best explanation
> will be "in-paralogs". But if you have a duplication event in a species (possible
> evidence could come from comparative genomics) you cannot necessarily conclude
> that the proteins must be unusually similar. In fact, looking for such events
> systematically and analysing divergence rates, would make an interesting project
> to quantify the evolutionary pressure on genes after duplication events.

This has been the focus of study for researchers such as Andras Wagner, looking at
the  innovation of interaction partners after duplication events using the
interactomes of different yeast strains and worm. Eugene Koonin et al have also
looked at this systematically, but I think a general (conceptually clean) framework
for this analysis would be a major step forward.


> Best regards,
> Boris
> ---
> Boris Steipe
> University of Toronto
> Program in Proteomics & Bioinformatics
> Departments of Biochemistry & Molecular and Medical Genetics
> http://biochemistry.utoronto.ca/steipe
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