Hemizygous subtelomeres of an African trypanosome chromosome may account for over 75% of chromosome length

Abstract

African trypanosomes are parasitic protozoa that infect a wide range of mammals, including humans. These parasites remain extracellular in the mammalian bloodstream, where antigenic variation allows them to survive the immune response. The Trypanosoma brucei nuclear genome sequence has been published recently. However, the significant chromosome size polymorphism observed among strains and subspecies of T. brucei, where total DNA content may vary up to 30%, necessitates a comparative study to determine the underlying basis and significance of such variation between parasites. In addition, the sequenced strain (Tb927) presents one of the smallest genomes analyzed among T. brucei isolates; therefore, establishing polymorphic regions will provide essential complementary information to the sequencing project. We have developed a Tb927 high-resolution DNA microarray to study DNA content variation along chromosome I, one of the most size-variable chromosomes, in different strains and subspecies of T. brucei. Results show considerable copy number polymorphism, especially at subtelomeres, but are insufficient to explain the observed size difference. Additional sequencing reveals that >50% of a larger chromosome I consists of arrays of variant surface glycoprotein genes (VSGs), involved in avoidance of acquired immunity. In total, the subtelomeres appear to be three times larger than the diploid core. These results reveal that trypanosomes can utilize subtelomeres for amplification and divergence of gene families to such a remarkable extent that they may constitute most of a chromosome, and that the VSG repertoire may be even larger than reported to date. Further experimentation is required to determine if these results are applicable to all size-variable chromosomes.

Histone Deacetylase Activity Regulates Chemical Diversity in Aspergillus

“…1). Subtelomere lengths vary considerably among eukaryotes; while Kluyveromyces lactis subtelomeres span only about 30 kb (17), those of humans may reach over 300 kb in length (33), and in trypanosomes, subtelomeric regions may make up the majority of the chromosome (13). Production of SMs and expression of biosynthetic genes in the ⌬hdaA mutant.…”

Immune system recognition of Trypanosoma cruzi

“…And this may be only part of the story, as additional scanning of the assembled sequence reveals nearly 2000 additional ts homologous sequences ranging in size from 100 bases to >3000 bases (Weatherly et al, unpublished). Many of these ts genes and pseudogenes appear to be located at the ends of chromosomes, a position that is known to facilitate recombination in related trypanosomatids [29]. The potential for substantial variation in the ts genes is supported by the documentation of differences in different parasite strains in the complement of ts genes and it is hypothesized that these differences account for variation in immunodominance patterns following infection of mice with different parasite strains [20 ].…”

African trypanosomes: the genome and adaptations for immune evasion

“…While some VSGs are found in silent ESs, silent or basic copy VSGs are also present in extensive subtelomeric arrays as aneuploid single-copy regions attached to diploid chromosome cores [27] (Figure 4). Although the VSG repertoires of different T. brucei strains contain many common VSG variants [28], there is nonetheless strain-specific divergence of these VSG repertoires, presumably facilitating superinfection of a host by multiple strains of trypanosomes [29,30].…”