PNAS March 16, 1999 vol. 96 no. 6 2902-2906
Leishmania major Friedlin chromosome 1 has an unusual distribution of protein-coding genes
Abstract
Leishmania are evolutionarily ancient protozoans (Kinetoplastidae) and important human pathogens that cause a spectrum of diseases ranging from the asymptomatic to the lethal. The Leishmania genome is relatively small [≈34 megabases (Mb)], lacks substantial repetitive DNA, and is distributed among 36 chromosomes pairs ranging in size from 0.3 Mb to 2.5 Mb, making it a useful candidate for complete genome sequence determination. We report here the nucleotide sequence of the smallest chromosome, chr1. The sequence of chr1 has a 257-kilobase region that is densely packed with 79 protein-coding genes. This region is flanked by telomeric and subtelomeric repetitive elements that vary in number and content among the chr1 homologs, resulting in an ≈27.5-kilobase size difference. Strikingly, the first 29 genes are all encoded on one DNA strand, whereas the remaining 50 genes are encoded on the opposite strand. Based on the gene density of chr1, we predict a total of ≈9,800 genes in Leishmania, of which 40% may encode unknown proteins.
The Kinetoplastidae are flagellated protozoans found in terrestrial and aquatic environments that cause diseases in organisms ranging from plants to vertebrates. These diseases result in widespread human suffering and death, as well as considerable economic loss from infection of livestock, wildlife, and crops. In addition, kinetoplastids have been particularly valuable for the study of fundamental molecular and cellular phenomena, such as RNA editing (1), mRNA transsplicing (2), glycosylphosphatidylinositol-anchoring of proteins (3), antigenic variation (4), and telomere organization (5). The early evolutionary divergence of these organisms makes comparison of their sequences with those of other eukaryotes, as well as prokaryotes, useful for the identification of ancient conserved motifs, and their protein sequences may be a useful source of diversity for protein engineering.
The numerous human-infective Leishmania spp. cause a spectrum of diseases with pathologies ranging from the asymptomatic to the lethal, and there are correlations between species and disease type and severity (6). The Leishmania haploid genome content is ≈34 megabases (Mb; ref. 7), consisting of 36 chromosomes ranging in size from 0.3 Mb to 2.5 Mb (8). It contains ≈30% repeated sequence (9), half of which is a series of telomeric hexamer repeats, whereas the remainder comprises other simple sequence repeats, transposons, as well as tandem and dispersed gene families such as rRNA, spliced-leader, tubulin, and gp63. The Leishmania molecular karyotype is conserved between Leishmania strains and species (10) with most genes syntenic among species (8). There are modest chromosome size polymorphisms between strains and larger size polymorphisms between species. Thus, this organism is an ideal candidate for a genome-sequencing project to elucidate its full genetic complement. The Leishmania Genome Network, established with the support of the World Health Organization, initiated a coordinated effort to map and sequence the Leishmania genome (see www.ebi.ac.uk/parasites/leish.html). Leishmania major MHOM/IL/81/Friedlin (LmjF) was selected as the reference strain to be sequenced and a first-generation contig map of the LmjF genome was constructed by cosmid fingerprinting (7). We report here the complete sequencing of chromosome 1 (chr1), the smallest chromosome.
References
- ↵
- Stuart K
(1991) Annu Rev Microbiol 45:327–344, pmid:1720609.
- ↵
- Perry K,
- Agabian N
(1991) Experientia 47:118–128, pmid:2001714.
- ↵
- Krakow J L,
- Hereld D,
- Bangs J D,
- Hart G W,
- Englund P T
(1986) J Biol Chem 261:12147–12153, pmid:3745182.
- ↵
- Borst P,
- Rudenko G
(1994) Science 264:1872–1873, pmid:7516579.
- ↵
- Blackburn E H
(1991) Nature (London) 350:569–573, pmid:1708110.
- ↵
- Shaw J J,
- Lainson R
- Peters W,
- Killick-Kendrick R
(1987) in The Leishmaniases in Biology and Medicine, eds Peters W, Killick-Kendrick R (Academic, London), 1, pp 291–361.
- ↵
- Ivens A C,
- Lewis S M,
- Bagherzadeh A,
- Zhang L,
- Chang H M,
- Smith D F
(1998) Genome Res 8:135–145, pmid:9477341.
- ↵
- Wincker P,
- Ravel C,
- Blaineau C,
- Pages M,
- Jauffret Y,
- Dedet J,
- Bastien P,
- Dedet J P
(1996) Nucleic Acids Res 24:1688–1694, pmid:8649987.
- ↵
- Ellis J,
- Crampton J
- Hart D T
(1989) in Leishmaniasis: The Current Status and New Strategies for Control, ed Hart D T (Plenum, New York), pp 589–596.
- ↵
- Bastien P,
- Blaineau C,
- Pagès M
(1992) Subcell Biochem 18:131–187, pmid:1485351.
- ↵
- Ryan K A,
- Dasgupta S,
- Beverley S M
(1993) Gene 131:145–150, pmid:8370535.
- ↵
- Ravel C,
- Macari F,
- Bastien P,
- Pages M,
- Blaineau C
(1995) Mol Biochem Parasitol 69:1–8, pmid:7723776.
- ↵
- Bouffard G G,
- Idol J R,
- Braden V V,
- Iyer L M,
- Cunningham A F,
- Weintraub L A,
- Touchman J W,
- Mohr-Tidwell R M,
- Peluso D C,
- Fulton R S,
- et al.
(1997) Genome Res 7:673–692, pmid:9253597.
- ↵
- Wilson R,
- Ainscough R,
- Anderson K,
- Baynes C,
- Berks M,
- Bonfield J,
- Burton J,
- Connell M,
- Copsey T,
- Cooper J,
- et al.
(1994) Nature (London) 368:32–38, pmid:7906398.
- ↵
- Fu G,
- Barker D C
(1998) Nucleic Acids Res 26:2161–2167, pmid:9547275.
- ↵
- Fu G,
- Barker D C
(1998) BioTechniques 24:386–390, pmid:9526644.
- ↵
- Myler P J,
- Lodes M J,
- Merlin G,
- deVos T,
- Stuart K D
(1994) Mol Biochem Parasitol 66:11–20, pmid:7984172.
- ↵
- Myler P J,
- Venkataraman G M,
- Lodes M J,
- Stuart K D
(1994) Gene 148:187–193, pmid:7958944.
- ↵
- LeBowitz J H,
- Smith H Q,
- Rusche L,
- Beverley S M
(1993) Genes Dev 7:996–1007, pmid:8504937.
-
- Ullu E,
- Matthews K R,
- Tschudi C
(1993) Mol Cell Biol 13:720–725, pmid:8417363.
- ↵
- Matthews K R,
- Tschudi C,
- Ullu E
(1994) Genes Dev 8:491–501, pmid:7907303.
- ↵
- Swindle J,
- Tait A
- Smith D F,
- Parsons M
(1996) in Molecular Biology of Parasitic Protozoa, eds Smith D F, Parsons M (Oxford Univ. Press, Oxford), pp 6–34.
- ↵
- Wong A K C,
- Curotto de Lafaille M A,
- Wirth D F
(1994) J Biol Chem 269:26497–26502, pmid:7929372.
-
- Lee M G S
(1996) Mol Cell Biol 16:1220–1230, pmid:8622666.
- ↵
- Dresel A,
- Clos J
(1997) Exp Parasitol 86:206–212, pmid:9225771.
- ↵
- Pays E,
- Vanhamme L
- Smith D F,
- Parson M
(1996) in Molecular Biology of Parasitic Protozoa, eds Smith D F, Parson M (Oxford Univ. Press, Oxford), pp 88–114.
- ↵
- Ravel C,
- Wincker P,
- Bastien P,
- Blaineau C,
- Pagès M
(1995) Mol Biochem Parasitol 74:31–41, pmid:8719243.
- ↵
- Myler P J,
- Tripp C A,
- Thomas L,
- Venkataraman G M,
- Merlin G,
- Stuart K D
(1993) Mol Biochem Parasitol 62:147–152, pmid:8114820.
- ↵
- Soto M,
- Requena J M,
- Garcia M,
- Gómez L C,
- Navarrete I,
- Alonso C
(1993) J Biol Chem 268:21835–21843, pmid:8408038.
- ↵
- Goffeau A,
- Barrell B G,
- Bussey H,
- Davis R W,
- Dujon B,
- Feldmann H,
- Galibert F,
- Hoheisel J D,
- Jacq C,
- Johnston M,
- et al.
(1996) Science 274:546, pmid:8849441, , 563–567..
- ↵
- Gardner M J,
- Tettelin H,
- Carucci D J,
- Cummings L M,
- Aravind L,
- Koonin E V,
- Shallom S,
- Mason T,
- Yu K,
- Fujii C,
- et al.
(1998) Science 282:1126–1132, pmid:9804551.
- ↵
- The C. elegans Sequencing Consortium
(1998) Science 282:2012–2018, pmid:9851916.
- ↵
- Tait A
(1983) Parasitol 86:29–57, pmid:6346233.
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