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UNCOVERING PSEUDOGENES AND INTERGENIC PROTEIN-CODING SEQUENCES IN TRITRYPS’ GENOMES
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Fundação Oswaldo Cruz. Vice-Diretoria de Desenvolvimento Tecnológico, Bio-Manguinhos. Instituto de Tecnologia em Imunobiológicos. Laboratório de Tecnologia Imunológica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.
Universidad de la República del Uruguay. Unidad de Genómica Evolutiva, Sección Biomatemática. Montevideo, Uruguay.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Molecular de Microrganismos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Molecular de Microrganismos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.
Universidad de la República del Uruguay. Unidad de Genómica Evolutiva, Sección Biomatemática. Montevideo, Uruguay.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Molecular de Microrganismos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Molecular de Microrganismos. Rio de Janeiro, RJ, Brasil.
Abstract
Trypanosomatids belong to a remarkable group of unicellular, parasitic organisms of the order Kinetoplastida, an early diverging
branch of the phylogenetic tree of eukaryotes, exhibiting intriguing biological characteristics affecting gene expression
(intronless polycistronic transcription, trans-splicing, and RNA editing), metabolism, surface molecules, and organelles (compartmentalization
of glycolysis, variation of the surface molecules, and unique mitochondrial DNA), cell biology and life cycle
(phagocytic vacuoles evasion and intricate patterns of cell morphogenesis). With numerous genomic-scale data of several
trypanosomatids becoming available since 2005 (genomes, transcriptomes, and proteomes), the scientific community can
further investigate the mechanisms underlying these unusual features and address other unexplored phenomena possibly
revealing biological aspects of the early evolution of eukaryotes. One fundamental aspect comprises the processes and mechanisms
involved in the acquisition and loss of genes throughout the evolutionary history of these primitive microorganisms.
Here, we present a comprehensive in silico analysis of pseudogenes in three major representatives of this group: Leishmania
major, Trypanosoma brucei, and Trypanosoma cruzi. Pseudogenes, DNA segments originating from altered genes that lost
their original function, are genomic relics that can offer an essential record of the evolutionary history of functional genes, as
well as clues about the dynamics and evolution of hosting genomes. Scanning these genomes with functional proteins as
proxies to reveal intergenic regions with protein-coding features, relying on a customized threshold to distinguish statistically
and biologically significant sequence similarities, and reassembling remnant sequences from their debris, we found thousands
of pseudogenes and hundreds of open reading frames, with particular characteristics in each trypanosomatid: mutation
profile, number, content, density, codon bias, average size, single- or multi-copy gene origin, number and type of
mutations, putative primitive function, and transcriptional activity. These features suggest a common process of pseudogene
formation, different patterns of pseudogene evolution and extant biological functions, and/or distinct genome organization
undertaken by those parasites during evolution, as well as different evolutionary and/or selective pressures acting on distinct
lineages.
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