Subject: Ferritin genes in FlyBase
Dear Michael,
Our interest in Drosophila iron metabolism resulted in description of two
genes encoding ferritin subunits a couple of years ago. Unfortunately, then
we did not know much about these subunits and consequently we helped create
two entries in FlyBase that are not accurate any more. Here is a proposal
for changes that in our view would improve the current situation and will
prevent further perpetuation of our old confusion.
Proposed changes in the nomenclature of the Drosophila ferritin genes
Ferritin is the principal biological iron storage protein. Vertebrate
ferritins are large spherical molecules that are composed of 24 subunits,
generally of two types, designated H (heavy) and L (light), based upon
rather small differences in the size of human subunits. Unfortunately,
these differences in size are reversed in some animals (e. g. in Drosophila
and in other insects), even among the vertebrates, but the terminology, now
based upon sequence similarities, has been retained. Additional subunits
are present in some animals. H and L chains are products of separate, but
related, genes. Insects that have been studied so far also have two types
of subunits, encoded by different genes. D. melanogaster ferritin is
composed of three major subunits with apparent molecular masses of 25, 26,
and 28 kDa that are products of two distinct genes (Charlesworth et al.,
Eur. J. Biochem.,  247:470-475 , 1997). The 25-kDa and 26-kDa subunits are
derived from the same gene. Based on the apparent molecular masses of the
subunits, we initially proposed a nomenclature for these genes which was
adopted by FlyBase: Fer-H, for the 'heavy' 28-kDa chain, and Fer-L, for the
'light' 26-kDa and 25-kDa chains. When the complete sequences of both
subunit types from D. melanogaster were obtained, it became clear that the
sequence of the 'light' chain (FER-L, product of gene Fer-L) is more
similar to the vertebrate H chains and that of the 'heavy' chain (FER-H,
product of gene Fer-H) is closer to the vertebrate L chains. In order to
avoid further confusion and at the same time to conform to the widely
accepted terminology for vertebrate ferritins we adopted a more neutral
designation of the Drosophila ferritin subunits and the corresponding
genes. This is reflected in the GenBank entry for the first Drosophila
ferritin sequence, the one for the 25-kDa and 26-kDa subunits, with
accession number U91524. In this entry we designate the sequence as coding
for the 'ferritin subunit 1', the protein as 'FER1', and the gene as
'Fer1'. This was adopted by other investigators and used in their GenBank
entries with accession numbers Y15629, Y15630, Y15631, Y15632, and Y15633.
The sequence of the 28-kDa subunit, derived from ESTs obtained by BDGP, we
designate as 'ferritin subunit 2', the protein as 'FER2', and the gene as
'Fer2'. In these neutral names for the subunits of Drosophila ferritin (and
similarly for the ferritin subunits of at least two other insect species)
the important fact that they resemble the vertebrate H and L chains
respectively is not evident. This may leave the impression that Drosophila
ferritins are composed of two types of subunits but with sequences more
similar to vertebrate H chains than to vertebrate L chains, as it is the
case in the trematode worm Schistosoma mansoni (Dietzel et al., Molec.
Biochem. Parasitol.,  50:245-254 , 1992) and in the nematode Caenorhabditis
elegans (unpublished observation). Now we know that not only Drosophila,
but other insects as well, have ferritins composed of at least two types of
subunits homologous to vertebrate H and L chains. To indicate this
important finding we propose the neutral names for the Drosophila subunits
to be amended with the descriptions 'heavy chain homologue' and 'light
chain homologue' abbreviated as 'HCH' and 'LCH' respectively. We have
already used the name 'ferritin heavy chain homologue' and the
abbreviations 'FER1 HCH' and 'Fer1 HCH' for the 'ferritin subunit 1' in a
recent publication (Georgieva et al., Proc. Natl. Acad. Sci. USA,
 96:2716-2721 , 1999). We retain the number '1' in the name of the subunit
for two reasons: (1) additional HCH or LCH subunits may be found and
eventually given different numbers and (2) the name 'ferritin subunit 1'
from our original GenBank entry was adopted and used by others, including
in a number of EST entries generated by BDGP.
We propose the following changes in the FlyBase entries for the ferritin genes:
			Current			New
_______________________________________________________________________________
			Gene Fer-L		Gene Fer1HCH
Symbol			Fer-L			Fer1HCH
Full name		Ferritin-Light		Ferritin 1 heavy chain
homologue
Function of product	ferritin light chain	ferritin heavy chain homologue
Cytological location	99F6--11		99F1-2
_______________________________________________________________________________
			Gene Fer-H		Gene Fer2LCH
Symbol			Fer-H			Fer2LCH
Full name		Ferritin-Heavy		Ferritin 2 light chain
homologue
Function of product	ferritin heavy chain	ferritin light chain homologue
Cytological location		-		99F1-2
We believe that the proposed changes fully reflect the current knowledge
on Drosophila and other insect ferritins. In our view the implementation
and dissemination of the new names of the ferritin genes trough FlyBase
will prevent further use of the old inaccurate names that were a result of
our own confusion. We hope that FlyBase will find our arguments solid
enough and will accept the proposed changes.
Sincerely,
Boris C. Dunkov					John H. Law
Department of Biochemistry			Department of Biochemistry
University of Arizona				University of Arizona
BSW 351						BSW 345
Tucson, AZ 85721				Tucson, AZ 85721