Stage-specific expressions of four different ribonuclease H genes in Leishmania

The human pathogen of the genus Leishmania cause worldwide morbidity and infection of visceral organs by some species may be lethal. Lack of rational chemotherapy against these pathogens dictates the study of differential biochemistry and molecular biology of the parasite as compared to its human host. The ubiquitous enzyme ribonuclease H (RNase H, EC 3.1.26.4) cleaves the RNA from a RNA:DNA duplex and is critical for the replication of DNA in the nucleus and the mitochondria. We have characterized four RNase H genes from Leishmania: one is of type I (LRNase HI) and three others are of type II (LRNase HIIA, -HIIB and -HIIC). In contrast human cells have only one type I and one type II RNase H. All the four RNase H genes in Leishmania are single copy and located in discrete chromosomes. When expressed inside RNase H-deficient E. coli, all of the four Leishmania RNase H were capable to complement the genetic defect of the E. coli, indicating their identity as RNase H. The enzymes are differentially expressed in the promastigotes and the amastigotes, the forms that thrives in entirely different physico-chemical conditions in nature. Nucleotide sequences of the 5'-UTRs of three of these mRNAs have upstream open reading frames. Understanding the regulation of these four distinct ribonuclease H genes in Leishmania will help us better understand leishmanial parasitism and may help us to design rational chemotherapy against the pathogen

Evolution of ribonuclease H genes in prokaryotes to avoid inheritance of redundant genes

<p>Abstract</p> <p>Background</p> <p>A theoretical model of genetic redundancy has proposed that the fates of redundant genes depend on the degree of functional redundancy, and that functionally redundant genes will not be inherited together. However, no example of actual gene evolution has been reported that can be used to test this model. Here, we analyzed the molecular evolution of the ribonuclease H (RNase H) family in prokaryotes and used the results to examine the implications of functional redundancy for gene evolution.</p> <p>Results</p> <p>In prokaryotes, RNase H has been classified into RNase HI, HII, and HIII on the basis of amino acid sequences. Using 353 prokaryotic genomes, we identified the genes encoding the RNase H group and examined combinations of these genes in individual genomes. We found that the RNase H group may have evolved in such a way that the RNase HI and HIII genes will not coexist within a single genome – in other words, these genes are inherited in a mutually exclusive manner. Avoiding the simultaneous inheritance of the RNase HI and HIII genes is remarkable when RNase HI contains an additional non-RNase H domain, double-stranded RNA, and an RNA-DNA hybrid-binding domain, which is often observed in eukaryotic RNase H1. This evolutionary process may have resulted from functional redundancy of these genes, because the substrate preferences of RNase HI and RNase HIII are similar.</p> <p>Conclusion</p> <p>We provide two possible evolutionary models for RNase H genes in which functional redundancy contributes to the exclusion of redundant genes from the genome of a species. This is the first empirical study to show the effect of functional redundancy on changes in gene constitution during the course of evolution.</p