Simulated pathogenic conformational switch regions matched well with the biochemical findings

Pathogenic conformational conversion is a general causation of many disease, such as transmissible spon- giform encephalopathy (TSE) caused by misfolding of prion, sickle cell anemia, and etc. In such structural changes, misfolding occurs in regions important for the stability of native structure firstly. This destabi- lizes the normal conformation and leads to subsequent errors in folding pathway. Sites involved in the first stage can be deemed switch regions of the protein, and are vital for conformational conversion. Namely it could be a switch of disease at residue level. Here we report an algorithm that can identify such sites computationally with an accuracy of 93%, by calculating the probability of the native structure of a short segment jumping to a mistake one. Knowledge of such switch sites could be used to target clinical therapy, study physiological and pathologic mechanism of protein, and etc.

Cross-species chromosome painting in the Perissodactyla: delimitation of homologous regions in Burchell's zebra (Equus burchellii) and the white (Ceratotherium simum) and black rhinoceros (Diceros bicornis)

Conserved chromosomal segments in the black rhinoceros, Diceros bicornis (DB1, 2n = 84), and its African sister-species the white rhinoceros, Ceratotherim simum (CSI, 2n = 82), were detected using Burchell's zebra (Equus burchellii, EBU, 2n = 44) chromosome-specific painting probes supplemented by a subset of those developed for the horse (Equus caballus, ECA, 2n = 64). In total 41 and 42 conserved autosomal segments were identified in C simum and D. bicornis respectively. Only 21 rearrangements (20 fissions and I fusion) are necessary to convert the Burchell's zebra karyotype into that of the white rhinoceros. One fission distinguishes the D. bicornis and C simum karyotypes which, excluding hetero- chromatic differences, are identical in all respects at this level of resolution. Most Burchell's zebra chromosomes correspond to two rhinoceros chromosomes although in four instances (EBU 18, 19, 20 and 21) whole chromosome synteny has been retained among these species. In contrast, one rhinoceros chromosome (DBI1, CSI1) comprises two separate Burchell's zebra chromosomes (EBU11 and EBU17). In spite of the high diploid numbers of the two rhinoceros species their karyotypes are surprisingly conserved offering a glimpse of the putative ancestral perissodactyl condition and a broader understanding of genome organization in mammals. Copyright (C) 2003 S. Karger AG, Base

Cross-species chromosome painting in the golden mole and elephant-shrew: support for the mammalian clades Afrotheria and Afroinsectiphillia but not Afroinsectivora

Cross-species painting (fluorescence in situ hybridization) with 23 human (Homo sapiens (HSA)) chromosome-specific painting probes (HSA 1-22 and the X) was used to delimit regions of homology on the chromosomes of the golden mole (Ghrysochloris asiaticus) and elephant-shrew (Elephantulus rupestris). A cladistic interpretation of our data provides evidence of two unique associations, HSA 1/19p and 5/21/3, that support Afrotheria. The recognition of HSA 5/3/21 expands on the 3/21 synteny originally designated as an ancestral state for all eutherians. We have identified one adjacent segment combination (HSA2/8p/4) that is supportive of Afroinsectiphillia (aardvark, golden mole, elephant-shrew). Two segmental combinations (HSA 10q/17 and HSA 3/20) unite the aardvark and elephant-shrews as sister taxa. The finding that segmental syntenies in evolutionarily distant taxa can improve phylogenetic resolution suggests that they may be useful for testing sequence-based phylogenies of the early eutherian mammals. They may even suggest clades that sequence trees are not recovering with any consistency and thus encourage the search for additional rare genomic changes among afrotheres.

CpG islands or CpG clusters: how to identify functional GC-rich regions in a genome?

Background: CpG islands (CGIs), clusters of CpG dinucleotides in GC-rich regions, are often located in the 5' end of genes and considered gene markers. Hackenberg et al. ( 2006) recently developed a new algorithm, CpGcluster, which uses a completely diffe

Variety of antimicrobial peptides in the Bombina maxima toad and evidence of their rapid diversification

Antimicrobial peptides secreted by the skin of many amphibians play an important role in innate immunity. From two skin cDNA libraries of two individuals of the Chinese red belly toad (Bombina maxima), we identified 56 different antimicrobial peptide cDNA sequences, each of which encodes a precursor peptide that can give rise to two kinds of antimicrobial peptides, maximin and maximin H. Among these cDNA, we found that the mean number of nucleotide substitution per non-synonymous site in both the maximin and maximin H domains significantly exceed the mean number of nucleotide substitution per synonymous site, whereas the same pattern was not observed in other structural regions, such as the signal and propiece peptide regions, suggesting that these antimicrobial peptide genes have been experiencing rapid diversification driven by Darwinian selection. We cloned and sequenced seven genes amplified from skin or liver genomic DNA. These genes have three exons and share the same gene structure, in which both maximin and maximin H are encoded by the third exon. This suggests that alternative splicing and somatic recombination are less likely to play a role in creating the diversity of maximins and maximin Hs. The gene trees based on different domain regions revealed that domain shuffling or gene conversion among these genes might have happened frequently.