Aspectos moleculares da evolução do gene DARC em primatas / Molecular aspects of DARC gene evolution in primates

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

Genes involved in pathogen-host interactions are strongly affected by positive natural selection. The gene of blood Duffy antigen, also known as DARC (Duffy Antigen Receptor for Chemokines), has an important role in the invasion of red blood cells by the parasites that cause malaria, Plasmodium vivax in humans and Plasmodium knowlesi in other primates. The structure of the DARC gene is known, it was mapped in 1q22-q23 region of chromosome 1, and is composed by two exons separated by a large intron. In an African population a nucleic acid deletion in GATA-1 of the gene promoter is responsible for the non-expression of DARC on red blood cells and the resistance to invasion by P. vivax. Moreover, the DARC antigen acts as a promiscuous receptor for chemokines and is expressed in red blood cells, endothelial venules cells and other tissues. Because of this dual role, in this study we sequenced homologous regions of the DARC gene in monkeys of the New and Old World and using statistical methods we tried to detect positive natural selection in their evolutionary history. New mutations were not found at promoter or in coding region. The phylogenetic trees by the methods of maximum parsimony, maximum likelihood and neighbor-join showed similar topologies with three large monophyletic clades recognizable and with the Macaca fascicularis showing a poliphyletic profile. The test of positive selection by the methods of Nei-Gojobori, maximum likelihood by branchs and maximum likelihood by sites not shown, statistically, the action of positive selection on the DARC gene. But the maximum likelihood test using sites divided in domains showed that some regions of the DARC gene are subject to different selective pressures, but also failed to detect the signature of positive selection. The results indicate the presence of darwinian selection on P. vivax binding region, but the maximum likelihood tests used, apparently, do not have enough power to detect its signature. Moreover, the results suggest that P. vivax binding region is under the influence of two opposing selective pressures (positive selection exerted by the parasite and purifying selection exerced by chemokines) that can also explain the non-detection of positive selection.

ASSUNTO(S)

evolução gene darc seqüência gene darc evolution gene darc sequence gene darc

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