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Euk.genes that function and live together

Paul J Travers p_travers at icrf.icnet.uk
Wed Jun 21 12:26:35 EST 1995

In article
<Pine.SUN.3.91.950621083011.27504A-100000 at bonjour.cc.columbia.edu>,
Christopher G Winter <cgw1 at columbia.edu> wrote:

> What evidence is there that genes whose products
> function together, and are unrelated in sequence, are co-localized in the 
> genome -- a la operonic genes in prok's? 

There is a nice example in the MHC, where components of the proteasome
(which generates peptides), a peptide transporter (which transports
peptides from the cytosol into the ER) and the MHC class I molecules
(which binds peptides transported by the transporter and transports them
to the cell surface for recognition by CD8 T cells) are co-localised.  The
proteasome and peptide transporter genes lie less than a kb apart.  

   This is a particularly interesting example as there are two proteasome
components (called Lmp2 and Lmp7) and two genes (TAP1 and TAP2) encoding
each chain of a two chain peptide transporter, a member of the ABC family
of transporters.  The gene order is Lmp-TAP-Lmp-TAP (can't remember off
hand which number is where, I think it is Lmp2-TAP1-Lmp7-Tap2) but this
does not appear to arise by duplication of an ancestral Lmp-TAP unit.  The
Lmp subunits are induced by interferon and replace two constitutive
subunits in the proteasome, whose genes are elsewhere in the genome and
unlinked; the Lmp's are more closely related to their constitutive
counterparts than they are to each other.  

   So did the Lmp's duplicate from an Lmp-TAP unit and then the individual
Lmp's become duplicated and translocated to give rise to the constitutive
subunits?  Or did the constitutive subunits become duplicated and
translocated next to the TAP's?  Answers on a postcard please and the best
answer wins a major prize.

Although not conforming to your criteria, because they are related in
sequence, the DM genes in the MHC have a function, as yet not clearly
defined, in facilitating peptide binding to the MHC class II molecules. 


Paul J Travers                          phone : +44-(0)71-631-6862 (office)
ICRF Structural Biology Unit             "       "       "    6868 (lab)
Birkbeck College                          fax : +44-(0)71-631-6803
Malet Street
London WC1E 7HX                         email :  p_travers at icrf.icnet.uk
England                                    or :  paul at histo.cryst.bbk.ac.uk

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