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DNA to the defense

n to diversify its repertoire of VSG genes. Most of these genes are concentrated in subtelomeric regions, which in T. brucei, are hemizygous: only one copy of this region is present in the chromosome. In contrast, the gene-rich cores of T. brucei chromosomes are diploid, meaning that the standard two copies are present.

"The main observation from our work is that subtelomeres can dominate a chromosome to such an extent that a very small proportion of a chromosome is truly diploid," Melville explains. "These huge subtelomeres are largely non-coding DNA, yet they contain 'contingency genes' that the parasite multiplies and diversifies for future use."

In previous studies, Melville's group showed that trypanosome chromosomes were quite variable in size. "The range of size variation we observe in African trypanosomes far exceeds anything reported in other organisms to date," Melville says. "This, coupled with the potential size of the VSG repertoire in these huge subtelomeres suggests an unrivalled capacity for new immune-resistant strains of African trypanosomes."

Analysis of the genome sequence of T. brucei was published just last year, amid increasing calls for research into new control strategies for this neglected disease. The current study underscores this parasite's reputation as a master of adaptation, devoting unprecedented resources to avoiding immune attack. Since the VSG coat appears to prevent access to other non-variable parasite proteins, such capacity for variation further dims hopes for an effective vaccine for affected populations in rural Africa.


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Contact: Maria Smit
smit@cshl.edu
516-422-4127
Cold Spring Harbor Laboratory
3-Aug-2006


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