Widespread stable noncanonical peptides identified by integrated analyses of ribosome profiling and ORF features.

Studies have revealed dozens of functional peptides in putative 'noncoding' regions and raised the question of how many proteins are encoded by noncanonical open reading frames (ORFs). Here, we comprehensively annotate genome-wide translated ORFs across five eukaryotes (human, mouse, zebrafish, worm, and yeast) by analyzing ribosome profiling data. We develop a logistic regression model named PepScore based on ORF features (expected length, encoded domain, and conservation) to calculate the probability that the encoded peptide is stable in humans.

Low-input RNase footprinting for simultaneous quantification of cytosolic and mitochondrial translation.

We describe a low-input RNase footprinting approach for the rapid quantification of ribosome-protected fragments with as few as 1000 cultured cells. The assay uses a simplified procedure to selectively capture ribosome footprints based on optimized RNase digestion. It simultaneously maps cytosolic and mitochondrial translation with single-nucleotide resolution.

Dynamic sex chromosome expression in Drosophila male germ cells.

Given their copy number differences and unique modes of inheritance, the evolved gene content and expression of sex chromosomes is unusual. In many organisms the X and Y chromosomes are inactivated in spermatocytes, possibly as a defense mechanism against insertions into unpaired chromatin. In addition to current sex chromosomes, Drosophila has a small gene-poor X-chromosome relic (4) that re-acquired autosomal status.

Heterochromatin Stabilization Requires the Zinc-Finger Protein Small Ovary.

Heterochromatin-mediated repression is essential for controlling the expression of transposons and for coordinated cell type-specific gene regulation. The () locus was identified in a screen for female-sterile mutations in , and mutants show dramatic ovarian morphogenesis defects. We show that the null phenotype is lethal and map the locus to the uncharacterized gene , which encodes a nuclear zinc-finger protein that colocalizes with the essential Heterochromatin Protein 1 (HP1a).

Re-annotation of eight genomes.

The sequenced genomes of the phylogeny are a central resource for comparative work supporting the understanding of the non-mammalian model system. These have also facilitated evolutionary studies on the selected and random differences that distinguish the thousands of extant species of . However, full utility has been hampered by uneven genome annotation.

Drosophila melanogaster positive transcriptional elongation factors regulate metabolic and sex-biased expression in adults.

Background: Transcriptional elongation is a generic function, but is also regulated to allow rapid transcription responses. Following relatively long initiation and promoter clearance, RNA polymerase II can pause and then rapidly elongate following recruitment of positive elongation factors. Multiple elongation complexes exist, but the role of specific components in adult Drosophila is underexplored.

Sxl-Dependent, tra/tra2-Independent Alternative Splicing of the Drosophila melanogaster X-Linked Gene found in neurons.

Somatic sexual determination and behavior in Drosophila melanogaster are under the control of a genetic cascade initiated by Sex lethal (Sxl). In the female soma, SXL RNA-binding protein regulates the splicing of transformer (tra) transcripts into a female-specific form. The RNA-binding protein TRA and its cofactor TRA2 function in concert in females, whereas SXL, TRA, and TRA2 are thought to not function in males.

Expression profile and gene age jointly shaped the genome-wide distribution of premature termination codons in a Drosophila melanogaster population.

Widespread premature termination codon mutations (PTCs) were recently observed in human and fly populations. We took advantage of the population resequencing data in the Drosophila Genetic Reference Panel to investigate how the expression profile and the evolutionary age of genes shaped the allele frequency distribution of PTCs. After generating a high-quality data set of PTCs, we clustered genes harboring PTCs into three categories: genes encoding low-frequency PTCs (≤ 1.

Roles of young serine-endopeptidase genes in survival and reproduction revealed rapid evolution of phenotypic effects at adult stages.

Our recent study found that 30% of young genes were essential for viability that determines development through stages from embryo to pupae in Drosophila melanogaster, revealing rapidly evolving genetic components involved in the evolution of development. Meanwhile, many young genes did not produce complete lethal phenotype upon constitutive knockdown, suggesting that they may not be essential for viability. These genes, nevertheless, were fixed by natural selection, and might play an important functional role in their adult stage.

Increased complexity of gene structure and base composition in vertebrates.

How the structure and base composition of genes changed with the evolution of vertebrates remains a puzzling question. Here we analyzed 895 orthologous protein-coding genes in six multicellular animals: human, chicken, zebrafish, sea squirt, fruit fly, and worm. Our analyses reveal that many gene regions, particularly intron and 3' UTR, gradually expanded throughout the evolution of vertebrates from their invertebrate ancestors, and that the number of exons per gene increased.

Important role of indels in somatic mutations of human cancer genes.

Background: Cancer is clonal proliferation that arises owing to mutations in a subset of genes that confer growth advantage. More and more cancer related genes are found to have accumulated somatic mutations. However, little has been reported about mutational patterns of insertions/deletions (indels) in these genes.

Variation in the ratio of nucleotide substitution and indel rates across genomes in mammals and bacteria.

Rates of nucleotide substitution and insertion/deletion (indel) are known to vary across the functional components of a genome. Little attention has been paid, however, to the quantitative relationship between the two. Here we investigate the ratio of nucleotide substitutions to indels (S/I) in different regions of 4 primates, 70 bacteria, and 8 other genomes.

Evolutionary pattern of protein architecture in mammal and fruit fly genomes.

Mutations, which can alter amino acid constitution, contribute greatly to protein evolution. However, little is reported of their pattern during protein structural evolution. We investigated the distribution of non-synonymous single nucleotide polymorphisms (nsSNPs) and insertions/deletions (indels) along mammal and fruit fly proteins.