Comparative phylogenetic and expression analysis of small GTPases families in legume and non-legume plants.

BACKGROUND: Small monomeric GTPases act as molecular switches in several processes that involve polar cell growth, participating mainly in vesicle trafficking and cytoskeleton rearrangements. This gene superfamily has largely expanded in plants through evolution as compared with other Kingdoms, leading to the suggestion that members of each subfamily might have acquired new functions associated to plant-specific processes. Legume plants engage in a nitrogen-fixing symbiotic interaction with rhizobia in a process that involves polar growth processes associated with the infection throughout the root hair. To get insight into the evolution of small GTPases associated with this process, we use a comparative genomic approach to establish differences in the Ras GTPase superfamily between legume and non-legume plants. RESULTS: Phylogenetic analyses did not show clear differences in the organization of the different subfamilies of small GTPases between plants that engage or not in nodule symbiosis. Protein alignments revealed a strong conservation at the sequence level of small GTPases previously linked to nodulation by functional genetics. Interestingly, one Rab and three Rop proteins showed conserved amino acid substitutions in legumes, but these changes do not alter the predicted conformational structure of these proteins. Although the steady-state levels of most small GTPases do not change in response to rhizobia, we identified a subset of Rab, Rop and Arf genes whose transcript levels are modulated during the symbiotic interaction, including their spatial distribution along the indeterminate nodule. CONCLUSIONS: This study provides a comprehensive study of the small GTPase superfamily in several plant species. The genetic program associated to root nodule symbiosis includes small GTPases to fulfill specific functions during infection and formation of the symbiosomes. These GTPases seems to have been recruited from members that were already present in common ancestors with plants as distant as monocots since we failed to detect asymmetric evolution in any of the subfamily trees. Expression analyses identified a number of legume members that can have undergone neo- or sub-functionalization associated to the spatio-temporal transcriptional control during the onset of the symbiotic interaction.

The most severe forms of type I autoimmune hepatitis are associated with genetically determined levels of TGF-beta1.

We previously reported that paediatric (PAH) and adult (AAH) forms of type I autoimmune hepatitis (AH) have different HLA-associations and clinical outcome. In the present study we investigated the role of TGF-beta1 genetic polymorphisms in the different outcome of PAH and AAH. We found a significant increase of "high producer" 25GG genotype in PAH and 10CC in AAH. Low inflammation and low fibrosis in AAH was associated with the increase of codon 10CC (high producer) and codon 25CC (low producer) genotypes. The analysis in AAH of the two positions-haplotypes revealed that combined presence of 25GG and 10CC seems to neutralize the 10CC effect which remained in AAH having the 10CC(+)-25GG(-) haplotype. Altogether these results may explain, at least partially, the different clinical outcome of AAH and PAH.

Gender susceptibility to chronic hepatitis C virus infection associated with interleukin 10 promoter polymorphism.

Elevated levels of interleukin 10 (IL-10) were previously described for chronically hepatitis C virus (HCV)-infected patients. We determined by a sequence-specific oligonucleotide probing technique the IL-10 promoter genotypes in 286 Argentinean HCV patients grouped according to disease outcome. The GG genotype (position -1082) is known to be associated with high IL-10 production, GA is considered an intermediate producer, and AA is associated with low IL-10 production. We found an increase in frequency of the GG genotype in female patients who do not eliminate the virus (RNA(+)). In these patients, the GG frequency was 0.19, versus 0.10 in controls (P = 0.03). This association became more significant in those RNA(+) female patients with elevated hepatic transaminases (GG frequency of 0.25; P = 0.0013). Additionally, this genotype frequency was higher in noncirrhotic female patients than in controls (GG frequency for noncirrhotic female patients was 0.31; P = 0.009). In RNA(-) patients, the GA frequency was elevated compared with that in controls (GA frequency of 0.76 in RNA(-) patients versus 0.48 in controls; P = 0.01), that in all HCV patients (GA frequency of 0.43; P = 0.001), and that in RNA(+) patients (GA frequency of 0.40; P = 0.0005). We conclude that a gender effect is observed with women carrying the GG high IL-10 producer genotype. The higher levels of IL-10 present in those individuals are associated with a higher risk of an inefficient clearance of the HCV and the development of a chronic HCV infection together with a lower risk of progression to cirrhosis in female patients.