TY - JOUR
T1 - DNA metabolism and genetic diversity in Trypanosomes
AU - Machado, Carlos Renato
AU - Augusto-Pinto, Luiz
AU - McCulloch, Richard
AU - Teixeira, Santuza M.R.
N1 - Funding Information:
We are indebted to Dr. Carlos Menck (University of São Paulo) for critical reading of the manuscript and valuable suggestions. Work in Carlos Renato Machado and Santuza M.R. Teixeira laboratories is supported by grants from Conselho Nacional de Pesquisas (CNPq), Comissão de Aperfeiçoameno de Pessoal de Nível Superior (CAPES/COFECUB), World Health Organization and Fundação de amparo a pesquisa de Minas Gerais (FAPEMIG). Luiz Augusto-Pinto received a doctoral fellowship from CNPq. Richard McCulloch is a Royal Society University Research Fellow, and work in his lab has been supported by the Wellcome Trust and the Medical Research Council. Figs. 1 and 2 are adapted from Trends in Parasitology, Vol. 20, Issue 3, Richard McCulloch, Antigenic variation in African Trypanosomes: monitoring progress, Pages 117–121, Copyright (2004), with permission from Elsevier.
PY - 2006/1
Y1 - 2006/1
N2 - Trypanosomes are protozoan parasites that cause major diseases in humans and other animals. Trypanosoma brucei and Trypanosoma cruzi are the etiologic agents of African and American Trypanosomiasis, respectively. In spite of large amounts of information regarding various aspects of their biology, including the essentially complete sequences of their genomes, studies directed towards an understanding of mechanisms related to DNA metabolism have been very limited. Recent reports, however, describing genes involved with DNA recombination and repair in T. brucei and T. cruzi, indicated the importance of these processes in the generation of genetic variability, which is crucial to the success of these parasites. Here, we review these data and discuss how the DNA repair and recombination machineries may contribute to strikingly different strategies evolved by the two Trypanosomes to create genetic variability that is needed for survival in their hosts. In T. brucei, two genetic components are critical to the success of antigenic variation, a strategy that allows the parasite to evade the host immune system by periodically changing the expression of a group of variant surface glycoproteins (VSGs). One component is a mechanism that provides for the exclusive expression of a single VSG at any one time, and the second is a large repository of antigenically distinct VSGs. Work from various groups showing the importance of recombination reactions in T. brucei, primarily to move a silent VSG into an active VSG expression site, is discussed. T. cruzi does not use the strategy of antigenic variation for host immune evasion but counts on the extreme heterogeneity of their population for parasite adaptation to different hosts. We discuss recent evidence indicating the existence of major differences in the levels of genomic heterogeneity among T. cruzi strains, and suggest that metabolic changes in the mismatch repair pathway could be an important source of antigenic diversity found within the T. cruzi population.
AB - Trypanosomes are protozoan parasites that cause major diseases in humans and other animals. Trypanosoma brucei and Trypanosoma cruzi are the etiologic agents of African and American Trypanosomiasis, respectively. In spite of large amounts of information regarding various aspects of their biology, including the essentially complete sequences of their genomes, studies directed towards an understanding of mechanisms related to DNA metabolism have been very limited. Recent reports, however, describing genes involved with DNA recombination and repair in T. brucei and T. cruzi, indicated the importance of these processes in the generation of genetic variability, which is crucial to the success of these parasites. Here, we review these data and discuss how the DNA repair and recombination machineries may contribute to strikingly different strategies evolved by the two Trypanosomes to create genetic variability that is needed for survival in their hosts. In T. brucei, two genetic components are critical to the success of antigenic variation, a strategy that allows the parasite to evade the host immune system by periodically changing the expression of a group of variant surface glycoproteins (VSGs). One component is a mechanism that provides for the exclusive expression of a single VSG at any one time, and the second is a large repository of antigenically distinct VSGs. Work from various groups showing the importance of recombination reactions in T. brucei, primarily to move a silent VSG into an active VSG expression site, is discussed. T. cruzi does not use the strategy of antigenic variation for host immune evasion but counts on the extreme heterogeneity of their population for parasite adaptation to different hosts. We discuss recent evidence indicating the existence of major differences in the levels of genomic heterogeneity among T. cruzi strains, and suggest that metabolic changes in the mismatch repair pathway could be an important source of antigenic diversity found within the T. cruzi population.
KW - DNA repair
KW - Genetic variability
KW - Recombination
KW - Trypanosoma
UR - http://www.scopus.com/inward/record.url?scp=29844439384&partnerID=8YFLogxK
U2 - 10.1016/j.mrrev.2005.05.001
DO - 10.1016/j.mrrev.2005.05.001
M3 - Articulo en revista no especializada
C2 - 16040270
AN - SCOPUS:29844439384
SN - 1383-5742
VL - 612
SP - 40
EP - 57
JO - Mutation Research - Reviews in Mutation Research
JF - Mutation Research - Reviews in Mutation Research
IS - 1
ER -