Nucleolar dominance and maternal control of 45S rDNA expression.

Using a system of interspecies hybrids, trihybrids, and recombinants with varying proportions of genomes from three distinct Xenopus species, we provide evidence for de novo epigenetic silencing of paternal 45 S ribosomal ribonucleic acid (rRNA) genes and their species-dependent expression dominance that escapes transcriptional inactivation after homologous recombination. The same pattern of imprinting is maintained in the offspring from mothers being genetic males (ZZ) sex-reversed to females, indicating that maternal control of ribosomal deoxyribonucleic acid (rDNA) expression is not sex-chromosome linked. Nucleolar dominance (nucleolus underdevelopment) in Xenopus hybrids appears to be associated with a major non-Mendelian reduction in the number of 45 S rDNA gene copies rather than a specific pattern of their expression. The loss of rRNA gene copies in F1 hybrids was non-random with respect to the parental species, with the transcriptionally dominant variant preferentially removed from hybrid zygotes. This dramatic disruption in the structure and function of 45 S rDNA impacts transcriptome patterns of small nucleolar RNAs and messenger RNAs, with genes from the ribosome and oxidative stress pathways being among the most affected. Unorthodoxies of rDNA inheritance and expression may be interpreted as hallmarks of genetic conflicts between parental genomes, as well as defensive epigenetic mechanisms employed to restore genome integrity.

Divergence of Drosophila melanogaster repeatomes in response to a sharp microclimate contrast in Evolution Canyon, Israel.

Repeat sequences, especially mobile elements, make up large portions of most eukaryotic genomes and provide enormous, albeit commonly underappreciated, evolutionary potential. We analyzed repeatomes of Drosophila melanogaster that have been diverging in response to a microclimate contrast in Evolution Canyon (Mount Carmel, Israel), a natural evolutionary laboratory with two abutting slopes at an average distance of only 200 m, which pose a constant ecological challenge to their local biotas. Flies inhabiting the colder and more humid north-facing slope carried about 6% more transposable elements than those from the hot and dry south-facing slope, in parallel to a suite of other genetic and phenotypic differences between the two populations. Nearly 50% of all mobile element insertions were slope unique, with many of them disrupting coding sequences of genes critical for cognition, olfaction, and thermotolerance, consistent with the observed patterns of thermotolerance differences and assortative mating.

Genome differentiation of Drosophila melanogaster from a microclimate contrast in Evolution Canyon, Israel.

The opposite slopes of "Evolution Canyon" in Israel have served as a natural model system of adaptation to a microclimate contrast. Long-term studies of Drosophila melanogaster populations inhabiting the canyon have exhibited significant interslope divergence in thermal and drought stress resistance, candidate genes, mobile elements, habitat choice, mating discrimination, and wing-shape variation, all despite close physical proximity of the contrasting habitats, as well as substantial interslope migration. To examine patterns of genetic differentiation at the genome-wide level, we used high coverage sequencing of the flies' genomes. A total of 572 genes were significantly different in allele frequency between the slopes, 106 out of which were associated with 74 significantly overrepresented gene ontology (GO) terms, particularly so with response to stimulus and developmental and reproductive processes, thus corroborating previous observations of interslope divergence in stress response, life history, and mating functions. There were at least 37 chromosomal "islands" of interslope divergence and low sequence polymorphism, plausible signatures of selective sweeps, more abundant in flies derived from one (north-facing) of the slopes. Positive correlation between local recombination rate and the level of nucleotide polymorphism was also found.

Functional proteomic pattern identification under low dose ionizing radiation.

OBJECTIVE: High dose radiation has been well known for increasing the risk of carcinogenesis. However, the understanding of biological effects of low dose radiation is limited. Low dose radiation is reported to affect several signaling pathways including deoxyribonucleic acid repair, survival, cell cycle, cell growth, and cell death. The goal of this study is to reveal the proteomic patterns influencing these pathways. METHODS AND MATERIALS: To detect the possibly regulatory proteins/kinases, an emerging reverse-phase protein microarray (RPPM) in conjunction with quantum dots nano-crystal technology is used as a quantitative detection system. The dynamic responses are observed under different time points and radiation doses. To quantitatively determine the responsive protein/kinases and to discover the network motifs, we present a discriminative feature pattern identification system (DFPIS). Instead of simply identifying proteins contributing to the pathways, our methodology takes into consideration of protein dependencies which are represented as strong jumping emerging patterns (SJEPs). Furthermore, infrequent patterns, though occurred, will be considered irrelevant. RESULTS: Computational results using DFPIS to analyze ataxia-telangiectasia mutated (ATM) cells treated under six different ionizing radiation doses (0cGy, 4cGy, 10cGy, 50cGy, 1Gy, and 5Gy) are presented. For each dose, the dynamic response was observed at different time points (1, 6, 24, 48, and 72h). The sets of different responsive proteins/kinases at different dose are reported. For each dose, the SJEPs for ATM-proficient and ATM-deficient cells are shown and compared. CONCLUSION: By using the new RPPM technology and the DFPIS algorithm, we can observe the change of signaling patterns even at a very low radiation dosage where conventional technologies tend to fail.

Biomarker selection and sample prediction for multi-category disease on MALDI-TOF data.

MOTIVATION: Diseases normally progress through several stages. Therefore, biomarkers corresponding to each stage may exist. To deal with such a multi-category problem, including sample stage prediction and biomarker selection, we propose methods for classification and feature selection. The proposed classification method is based on two schemes: error-correcting output coding (ECOC) and pairwise coupling (PWC). The final decision for a test sample prediction is an integration of these two schemes. The biomarker pattern for distinguishing each disease category from another one is achieved by the development of an extended Markov blanket (EMB) feature selection method. RESULTS: In this study, a liver cancer matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) dataset was used, which comprises hepatocellular carcinoma (HCC), cirrhosis, and healthy spectra. Peak patterns were discovered for distinguishing pairwise categories among the three classes. Importance and reliability of individual peaks were presented by the measurements of certain weight values and frequencies. The classification capability of the proposed approach was compared with classical ECOC, random forest, Naive Bayes, and J48 methods. AVAILABILITY: Supplementary materials are available at http://visionlab.uta.edu/biomarker/bioinfo.htm.