Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.

The epithelium is the major entry point for many viruses but the processes protecting barrier surfaces against viral infections are incompletely understood. We identify interleukin (IL)-22 produced by group 3 innate lymphoid cells (ILC3s) as an amplifier of interferon (IFN)-λ signaling, a synergism required to curtail replication of rotavirus, the leading cause of childhood gastroenteritis. Cooperation between IL-22 and IFN-λ receptors, both of which are preferentially expressed by intestinal epithelial cells, was required for optimal STAT1 transcription factor activation and expression of interferon-stimulated genes. This data suggests that epithelial cells are protected against virus replication by co-opting two evolutionarily related cytokine networks. These data may inform the design of novel immunotherapies of virus infections that are sensitive to IFNs.

Helicobacter pylori infects the stomachs of one in two humans and can cause sequelae that include ulcers and cancer. Here we sequenced the genomes of 97 H. pylori isolates from 52 members of two families living in rural conditions in South Africa. From each of 45 individuals, two H. pylori strains were isolated from the antrum and corpus parts of the stomach, and comparisons of their genomes enabled us to study within-host evolution. In 5 of these 45 hosts, the two genomes were too distantly related to be derived from each other and therefore represented evidence of multiple infections. From the remaining 40 genome pairs, we estimated that the synonymous mutation rate was 1.38 × 10 −5 per site per year, with a low effective population size within host probably reflecting population bottlenecks and immune selection. Some individuals showed very little evidence for recombination, whereas in others, recombination introduced up to 100-times more substitutions than mutation. These differences may reflect unequal opportunities for recombination depending on the presence or absence of multiple infections. Comparing the genomes carried by distinct individuals enabled us to establish probable transmission links. Transmission events were found significantly more frequently between close relatives, and between individuals living in the same house. We found, however, that a majority of individuals (27/52) were not linked by transmission to other individuals. Our results suggest that transmission does not always occur within families, and that coinfection with multiple strains is frequent and evolutionarily important despite a fast turnover of the infecting strains within-host.

The human stomach is a formidable barrier to orally ingested microorganisms and was long thought to be sterile. The discovery of Helicobacter pylori, a carcinogenic bacterial pathogen that infects the stomach mucosa of more than one half of all humans globally, has started a major paradigm shift in our understanding of the stomach as an ecological niche for bacteria. The special adaptations that enable H. pylori to colonize this well-protected habitat have been intensively studied over the last three decades. In contrast, our knowledge concerning bacteria other than H. pylori in the human stomach is still quite limited. However, a substantial body of evidence documents convincingly that bacteria can regularly be sampled from the stomachs of healthy adults. Commonly detected phyla include Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria, and characteristic genera are Lactobacillus, Streptococcus, and Propionibacterium. In this review, we summarize the available literature about the gastric microbiota in humans and selected model animals, discuss the methods used in its characterization, and identify gaps in our knowledge that need to be addressed to advance our understanding of the bacterial colonization of the different layers of the gastric mucosa and its potential role in health and disease.