tic distribu tion. As can be seen in Figure 1 and in the Additional file 6, in which we also analyzed the alleles present in preliminary assemblies of the JR cl4 and Esmeraldo cl3 genomes, 70 out of a total of 94 SNPs, were located in a natively unstructured C terminal tail. Besides being present in all trypanosomatids, this gene is also present in Trichomonas and in a a few other organisms www.selleckchem.com/products/chir-99021-ct99021-hcl.html such as Caenorhabditis, Cryptosporidium, and in one plant. Another interesting gene showing a striking accu mulation of non synonymous changes in a natively unstructured domain is the A2Rel like protein of T. cruzi, which was first des cribed in Leishmania. In this case the majority of SNPs identified are located in a disordered N terminal domain, as predicted by IUPred. Assessment of selection pressure in T.
Cruzi coding genes Because SNPs identified in this work represent variation observed within a species, we decided to use the nucleotide diversity indicator �� as an estimate of selection. In our set of high quality alignments, �� ranged between 0 and 0. 15. Not taking Inhibitors,Modulators,Libraries into account loci corresponding to singleton sequences, the remaining loci with nil values of �� were those for which we could not identify high quality SNPs. As seen in Figure 2, there is an ap parent enrichment of alignments with no SNPs identified. By inspecting the annotation of these genes, it is clear that many of these cases correspond to alignments containing highly identical copies of genes from large families. It has been observed already that many of these genes are organized in tandem arrays, where copies of the array display unusually Inhibitors,Modulators,Libraries high nucleotide identity values.
It Inhibitors,Modulators,Libraries is clear that the diversity observed in one of these alignments is not representative of the overall diversity that can be seen at the family level. Apart from these cases, alignments with low �� values were those of ribosomal proteins, histones and cytochromes among others. To assess the functional relevance of the nucleotide diver sity indicator, we looked at the distribution of �� in differ ent functional contexts, the functional annotation of the T. cruzi genome using the Molecular Function ontology, and the functional map ping of T. cruzi enzymes in metabolic pathways accor ding to the KEGG Metabolic Pathways database.
First, using a subset of terms from the Gene Ontology we grouped 2,158 alignments containing GO annotation into 27 broad Inhibitors,Modulators,Libraries classes as defined by their parent GO terms from the Molecular Entinostat Func tion ontology. There were significant differences in the �� values when comparing all classes using the non parametric Kruskal Wallis test. The categories showing less diversity were those with functions in oxidative stress response, protein ubiquitination, and those involved in RNA processing and translation. On the other extreme, classes showing a high nucleotide diversity moreover were those corresponding to integral membrane proteins, ion binding and retro transposons. In all cases, we observed a significant disper sio