Gene synteny and evolution of genome architecture in trypanosomatids
Introduction
Kinetoplastid protozoan parasites belong to a distinct evolutionary lineage of eukaryotes [1]. Within the kinetoplastids, members of the trypanosomatid family include etiological agents of several tropical diseases such as African sleeping sickness (Trypanosoma brucei), Chagas’ disease (Trypanosoma cruzi), and cutaneous leishmaniasis (Leishmania major). According to the most recent studies, Trypanosoma and Leishmania last shared a common ancestor between 400 and 600 Ma [2], [3], [4], their divergence predating by far the emergence of mammals some 165 Ma [5]. Together, these three pathogens are responsible for more than 20 million human infections annually. They employ different immune evasion strategies with T. brucei undergoing antigenic variation of the surface coat [6], whereas L. major and T. cruzi adopt an intracellular lifestyle and invade host cells. Leishmania species exclusively elect residence within the parasitophorous vacuole of macrophages, whose role is to ingest and kill invaders. The genetic basis for these differences in parasitic modes is unknown.
In a first large-scale comparative genomics study in trypanosomatids, we analyzed the level of synteny (conservation of gene order) among these three organisms by looking at homologous chromosomal segments. Analysis of synteny allows the close examination of the selective and mutational forces that act on chromosomal and genome structure. In addition, comparative gene annotation provides substantial aid in the assignment of orthology of genes across species since genes found in similar locations are frequently orthologous. We report in this paper the existence of a strong conservation of gene order in trypanosomatids and evidence for selective forces that appear to maintain the large directional clusters observed in these organisms [7], [8], [9]. Where differences between the species exist, interruption of synteny and genome rearrangement events are punctuated by the presence of retrotransposon-like elements or members of a gene family that has been shown to contain hot spots for retrotransposon insertion. The data suggest that retrotransposons likely played an important role in shaping trypanosomatid genome organization and evolution.
Section snippets
Strains sequenced
The trypanosomatid reference strains being sequenced as part of multi-center collaborations are T. brucei, stock TREU927/4 single VAT derivative GuTat10.1; L. major MHOM/1L/81/Friedlin; and T. cruzi, CL Brener.
Leishmania major
The sequences used for this study comprise a 119 kb contig from L. major chromosome 12 (LmChr12; GenBank accession AL390114), a 200 kb contig from chromosome 15 (LmChr15; accession AL160371), and a 70 kb contig from chromosome 26 (LmChr26; accession AL160493). All three chromosomes are
Results and discussion
To examine the level of synteny among the trypanosomatids, we identified T. brucei and T. cruzi chromosome segments that are homologous to the first fully sequenced chromosome from this order, L. major chromosome 1 (LmChr1). LmChr1 genes are arranged into two directional gene clusters, transcribed in opposite directions, separated by a 1.6 kb strand-switch region [7]. These alignments reveal that the level of synteny among the three organisms is extensive (Fig. 1a). Of the 79 CDSs reported on Lm
Acknowledgements
The work at the Institute for Genomic Research (TIGR), the Seattle Biomedical Research Institute (SBRI) and the Karolinska Institute was supported by grants from the National Institute for Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH) to N.E.S. (AI43062, AI45038), K.S. (AI49599, AI45039) and B.A. (AI45061). The work at the Sanger Institute was supported by grants from the Wellcome Trust. The authors would like to acknowledge John Donelson and Joanna DaSilva for
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Present address: Case Western Reserve University, OH 44106, USA.