The following text derives from a letter published in Parasitology Today (vol 13 no. 11, pp 416-417, November 1997). Copyright in the original article is vested in Elsevier.

A Unified Nomenclature for Filarial Genes

Mark Blaxter, David Guiliano, Alan Scott and Steven Williams
the founding members of F.U.N.K. (the Filarial Unified Nomenclature Kommittee)

The application of advanced molecular methods to the analysis of filarial nematode genes and genomes has led to an explosion in the number of genes and gene products which have been identified and studied. The nature of the scientific discovery process has inevitably led to the same gene being cloned in different laboratories simultaneously. This in turn means that a single gene can have multiple names in the literature leading to unnecessary confusion. The success of expressed sequence tag (EST) projects on Brugia malayi, Onchocerca volvulus and Wuchereria bancrofti means that there are now thousands of identified filarial genes in the public databases [1, 2]. We suggest that the genetic nomenclature for parasitic nematodes proposed by Bird and Riddle [3] should be adopted by the filarial research community as the harvesting of the fruits of the EST and genome sequencing projects begins. Here we outline the basis of the nomenclature and give illustrations of its application.

The goal of the nomenclature system is to ensure that expressed genes are given unique and permanant labels. It is proposed that this occurs at two levels. The first will be at the level of nucleotide sequence where a mechanism for identifying multiple sequences which are derived from a single gene will be used to provide each gene with a unique cluster identifier. As selected genes are characterized and the functional significance of the protein product is appreciated, a second label will be appled that will convey information on the protein's biological role.

The WHO-sponsored Brugia EST project has developed a clustering system for DNA sequences that provides a mechanism for identification and grouping of multiple ESTs derived from a single gene (D Guiliano and J. Callahan, unpublished). The EST sequences are compared to each other and grouped by sequence identity. Each cluster is given a unique and permanent identifier: "BMC00000" where BMc stands for Brugia malayi expressed sequence cluster and 00000 is a five digit number. This cluster identifier can thus be used to refer to all of the subsumed ESTs. The cluster identifiers are permanent, in that a particular BMc cluster designation will only be used for one cluster. Provision is made in the naming scheme for "retiring" cluster names. This can happen when either (1) a cluster is found to be misformed due to erroneous inclusion of members of a closely related gene family or due to a chimaeric sequence (which derives from two distinct genes), or (2) when a cluster is subsequently found to be subsumed by another (when a longer sequence or bridging sequence becomes available). The primary clusters have been "seeded" using gene sequences already available in GenBank, so that ESTs deriving from already cloned genes can be tagged correctly. We propose that similar clustering is carried out on the Onchocerca (OVC00000), Wuchereria (WBC00000) and other filarial datasets. The register of cluster numbers will be held by the Filarial Genome Resource Center (Smith College, MA). The Brugia project is also performing a cluster analysis on lifecycle subsets of the EST data so that numbers of genes expressed in each stage can be assessed: these analyses will be reported with reference to the BM cluster identifiers. The cluster designations will be made public through the Filarial Genome Project world wide web site (http://helios.bto.ed.ac.uk/mbx/fgn/filgennet.html, mirrored at http://math.smith.edu/~sawlab/fgn/filgen1.html).

Genes which are taken futher, perhaps by their being sequenced in full or otherwise studied, should be given single names that communicate a significant aspect of the biological role of the gene product. For this we propose the system first used by the Caenorhabditis elegans community [4, 5] and described for use in parasitic nematodes by Bird and Riddle [3]. The Bird and Riddle scheme includes extensive and complete rules for designation of strains, alleles, chromosomal rearrangements and molecular clones, and should be consulted for details. Here we outline the gene and gene-product naming scheme.

Specific gene families (such as actin or tubulin genes), or a general gene group (such as abundant larval transcripts) are given a three letter designation that should preferably be pronouncable and should not contain the initials of the species or the stage from which it was derived. Designators which include terms such as "nematode" and "worm" are also discouraged. The use of established three-letter designations for conserved gene products (such as myo for myosin or tpx for thioredoxin peroxidase) will be encouraged by the nomenclature committee (Table 1). Thus for the above examples, act for actin and alt for abundant larval transcript would be acceptable. Following the gene name should be an arabic numerical accession numeral separated by a hyphen. Pseudogenes are further designated by the letters ps. Thus we might have act-1, act-2, and act-3ps for three actin genes, one of which is a pseudogene. The taxonomic origin of each gene can be given by a two-letter italicised genus-species designator placed before the gene name (Table 2). The nucleotide sequence of named genes are designated by italicised, lower-case letters: Bm-act-1, for example. The protein products of named genes are designated by a capitalised, nonitalic version of the gene name: Bm-ACT-1 for example.

The Filarial Unified Nomenclature Kommittee (Alan Scott, Steven Williams, David Guiliano and Mark Blaxter) will act as oversight committee for the nomenclature, in particular for ensuring that three-letter gene designations are not used more than once, and that a common naming and numbering scheme is used. We encourage all researchers to submit their designations to us for entry into a register of gene names, and we will liase with the Society of Nematologists naming committee to ensure compliance with their rules. The register will be publicly accessible over the world wide web through the Filarial Genome Project site.

We encourage all researchers to use the cluster identifiers and gene names in publications and papers. The gene name should be used in preference to the cluster identifier, but we would suggest that the first time a gene is mentioned, its BM cluster designation is also given, so that others can cross reference to the database. For example, a paper describing actins might include the text "We have designated this gene Bm-act-1 (Brugia malayi actin; EST cluster BMc00001)".

The Filarial Unified Nomeclature Kommittee was formed and met at the Edna McConnell Clark Ochocerciasis meeting at Woods Hole, 6-10 April 1997. Correspondance for FUNK should be addressed to mark.blaxter@ed.ac.uk.

Table 1: Some currently used three-letter gene names
FUNK maintains an up-to-date list of accepted gene names on this WWW site
 

gene name	description	reference
act	actin	6
col	collagen	7-9
alt	abundant larval transcript	10
gpx	glutathione peroxidase	11
tpx	thioredoxin peroxidase
efa-1	elongation factor 1 - alpha	10
spn	serpin	12
cpi	cysteine protease inhibitor (cystatin)	10,13
tub	beta tubulin	14
tua	alpha tubulin	14

Table 2: Proposed abbreviations for species binomen prefix for filarial nematode genes.
 FUNK maintains an up-to-date list of accepted species prefixes on this WWW site
 

Abbreviation	Taxonomic binomial
Av	Acanthocheilonema viteae
Ba	Brugia patei
Bm	Brugia malayi
Bp	Brugia pahangi
Bt	Brugia timori
Di	Dirofilaria immitis
Ll	Loa loa
Ls	Litomosoides sigmodontis = L. carinii
Mp	Mansonella perstans
Ms	Mansonella streptocerca
Oc	Onchocerca cervicalis
Og	Onchocerca gibsoni
Oo	Onchocerca ochengi
Ot	Onchocerca guttarosa
Ov	Onchocerca volvulus
Wb	Wuchereria bancrofti
Wk	Wuchereria kalimantani

References

1 Blaxter, M.L. (1995) The Filarial Genome Project. Parasitology Today 11, 811-812

2 Blaxter, M.L., et al. (1996) Genes expressed in Brugia malayi infective third stage larvae. Mol. Biochem. Parasitol. 77, 77-96

3 Bird, D.M. and D.L. Riddle (1994) A genetic nomenclature for parasitic nematodes. J. Nematol. 26, 138-143

4 Horvitz, H.R., et al. (1979) A uniform genetic nomenclature for the nematode Caenorhabditis elegans. Mol. Gen. Genet. 175, 129-133

5 Hodgkin, J. (1997) Appendix1: Genetics. In D. Riddle, et al. (eds.), C. elegans II, Cold Spring Harbor Press, Cold Spring Harbor, NY pp. 881-1047

6 Zeng, W. and J.E. Donelson (1992) The actin genes of Onchocerca volvulus. Mol. Biochem. Parasitol. 55, 207-216

7 Scott, A.L., et al. (1995) Molecular cloning of the cuticular collagen Bmcol-2 from Brugia malayi. Mol. Biochem. Parasitol. 70, 221-225

8 Bisoffi, M. and B. Betschart (1996) Identification and sequence comparison of a cuticular collagen of Brugia malayi. Parasitology in press,

9 Caulagi, V.R., et al. (1991) Isolation and partial sequence of a collagen gene from the human filarial parasite Brugia malayi. Mol. Biochem. Parasitol. 45, 57-64

10 Gregory, W.F., et al. (1997) Diferentially expressed, abundant, trans-spliced cDNAs from larval Brugia malayi. Mol. Biochem. Parasitol. submitted,

11 Cookson, E., et al. (1992) Identification of the major soluble cuticular glycoprotein of lymphatic filarial nematode parasites as a secretory homologue of glutathione peroxidase. Proceedings of the National Academy of Sciences USA 89, 5837-5841

12 Yenbutr, P. and A.L. Scott (1995) Molecular cloning of a serine proteinase inhibitor from Brugia malayi. Infect. Immun. 63, 1745-1753

13 Lustigman, S., et al. (1992) Molecular cloning and characterisation of onchocystatin, a cysteine protease inhibitor of Onchocerca volvulus. J. Biol. Chem. 267, 17339-17346

14 Maina, C.V., et al. (1987) Dirofilaria immitis: Genomic complexity and characterisation of a structural gene. In A.J. MacInnis (ed.) Molecular Paradigms for Eradicating Helminthic Parasites, Alan R. Liss Inc., New York pp. 193-204