ABSTRACT
The adult human intestine contains trillions of bacteria, representing hundreds of species and thousands of subspecies. Little is known about the selective pressures that have shaped and are shaping this community's component species, which are dominated by members of the Bacteroidetes and Firmicutes divisions. To examine how the intestinal environment affects microbial genome evolution, we have sequenced the genomes of two members of the normal distal human gut microbiota, Bacteroides vulgatus and Bacteroides distasonis, and by comparison with the few other sequenced gut and non-gut Bacteroidetes, analyzed their niche and habitat adaptations. The results show that lateral gene transfer, mobile elements, and gene amplification have played important roles in affecting the ability of gut-dwelling Bacteroidetes to vary their cell surface, sense their environment, and harvest nutrient resources present in the distal intestine. Our findings show that these processes have been a driving force in the adaptation of Bacteroidetes to the distal gut environment, and emphasize the importance of considering the evolution of humans from an additional perspective, namely the evolution of our microbiomes.
Subject(s)
Bacteroides/genetics , Evolution, Molecular , Intestines/microbiology , Symbiosis/genetics , Adaptation, Physiological , Bacteriophages/genetics , Bacteroides/physiology , Bacteroides/virology , Conjugation, Genetic , DNA Transposable Elements , Ecosystem , Gene Duplication , Gene Transfer, Horizontal , Genetic Variation , Genome, Bacterial , Humans , Molecular Sequence Data , Phylogeny , Polysaccharides, Bacterial/biosynthesis , Polysaccharides, Bacterial/genetics , RNA, Bacterial/genetics , RNA, Ribosomal, 16S/genetics , Species SpecificityABSTRACT
Helicobacter pylori produces acute superficial gastritis in nearly all of its human hosts. However, a subset of individuals develops chronic atrophic gastritis (ChAG), a condition characterized in part by diminished numbers of acid-producing parietal cells and increased risk for development of gastric adenocarcinoma. Previously, we used a gnotobiotic transgenic mouse model with an engineered ablation of parietal cells to show that loss of parietal cells provides an opportunity for a H. pylori isolate from a patient with ChAG (HPAG1) to bind to, enter, and persist within gastric stem cells. This finding raises the question of how ChAG influences H. pylori genome evolution, physiology, and tumorigenesis. Here we describe the 1,596,366-bp HPAG1 genome. Custom HPAG1 Affymetrix GeneChips, representing 99.6% of its predicted ORFs, were used for whole-genome genotyping of additional H. pylori ChAG isolates obtained from Swedish patients enrolled in a case-control study of gastric cancer, as well as ChAG- and cancer-associated isolates from an individual who progressed from ChAG to gastric adenocarcinoma. The results reveal a shared gene signature among ChAG strains, as well as genes that may have been lost or gained during progression to adenocarcinoma. Whole-genome transcriptional profiling of HPAG1's response to acid during in vitro growth indicates that genes encoding components of metal uptake and utilization pathways, outer membrane proteins, and virulence factors are among those associated with H. pylori's adaptation to ChAG.
Subject(s)
Gastritis, Atrophic/microbiology , Genome, Bacterial/genetics , Helicobacter pylori/genetics , Adenocarcinoma/microbiology , Base Pairing , Chronic Disease , Disease Progression , Gene Expression Profiling , Gene Expression Regulation, Bacterial , Genomic Instability , Genotype , Helicobacter pylori/drug effects , Helicobacter pylori/growth & development , Humans , Hydrogen-Ion Concentration , Molecular Sequence Data , Oligonucleotide Array Sequence Analysis , Sequence Analysis, DNA , Stomach Neoplasms/microbiologyABSTRACT
Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.
Subject(s)
Chromosomes, Human, Pair 2/genetics , Chromosomes, Human, Pair 4/genetics , Animals , Base Composition , Base Sequence , Centromere/genetics , Conserved Sequence/genetics , CpG Islands/genetics , Euchromatin/genetics , Expressed Sequence Tags , Gene Duplication , Genetic Variation/genetics , Genomics , Humans , Molecular Sequence Data , Physical Chromosome Mapping , Polymorphism, Genetic/genetics , Primates/genetics , Proteins/genetics , Pseudogenes/genetics , RNA, Messenger/analysis , RNA, Messenger/genetics , RNA, Untranslated/analysis , RNA, Untranslated/genetics , Recombination, Genetic/genetics , Sequence Analysis, DNAABSTRACT
Human chromosome 7 has historically received prominent attention in the human genetics community, primarily related to the search for the cystic fibrosis gene and the frequent cytogenetic changes associated with various forms of cancer. Here we present more than 153 million base pairs representing 99.4% of the euchromatic sequence of chromosome 7, the first metacentric chromosome completed so far. The sequence has excellent concordance with previously established physical and genetic maps, and it exhibits an unusual amount of segmentally duplicated sequence (8.2%), with marked differences between the two arms. Our initial analyses have identified 1,150 protein-coding genes, 605 of which have been confirmed by complementary DNA sequences, and an additional 941 pseudogenes. Of genes confirmed by transcript sequences, some are polymorphic for mutations that disrupt the reading frame.
Subject(s)
Chromosomes, Human, Pair 7 , Animals , Base Sequence , Gene Duplication , Humans , Mice , Molecular Sequence Data , Physical Chromosome Mapping , Proteins/genetics , Pseudogenes , RNA, Untranslated , Sequence Analysis, DNA , Species Specificity , Williams Syndrome/geneticsABSTRACT
The male-specific region of the Y chromosome, the MSY, differentiates the sexes and comprises 95% of the chromosome's length. Here, we report that the MSY is a mosaic of heterochromatic sequences and three classes of euchromatic sequences: X-transposed, X-degenerate and ampliconic. These classes contain all 156 known transcription units, which include 78 protein-coding genes that collectively encode 27 distinct proteins. The X-transposed sequences exhibit 99% identity to the X chromosome. The X-degenerate sequences are remnants of ancient autosomes from which the modern X and Y chromosomes evolved. The ampliconic class includes large regions (about 30% of the MSY euchromatin) where sequence pairs show greater than 99.9% identity, which is maintained by frequent gene conversion (non-reciprocal transfer). The most prominent features here are eight massive palindromes, at least six of which contain testis genes.
Subject(s)
Chromosomes, Human, Y/genetics , Evolution, Molecular , Sex Determination Processes , Transducin , Chromosomes, Human, X/genetics , Crossing Over, Genetic/genetics , DNA Transposable Elements/genetics , Euchromatin/genetics , Female , Gene Amplification/genetics , Gene Conversion/genetics , Genes/genetics , Heterochromatin/genetics , Humans , In Situ Hybridization, Fluorescence , Male , Models, Genetic , Multigene Family/genetics , Organ Specificity , Pseudogenes/genetics , Sequence Homology, Nucleic Acid , Sex Characteristics , Species Specificity , Testis/metabolism , Transcription, Genetic/geneticsABSTRACT
Eight palindromes comprise one-quarter of the euchromatic DNA of the male-specific region of the human Y chromosome, the MSY. They contain many testis-specific genes and typically exhibit 99.97% intra-palindromic (arm-to-arm) sequence identity. This high degree of identity could be interpreted as evidence that the palindromes arose through duplication events that occurred about 100,000 years ago. Using comparative sequencing in great apes, we demonstrate here that at least six of these MSY palindromes predate the divergence of the human and chimpanzee lineages, which occurred about 5 million years ago. The arms of these palindromes must have subsequently engaged in gene conversion, driving the paired arms to evolve in concert. Indeed, analysis of MSY palindrome sequence variation in existing human populations provides evidence of recurrent arm-to-arm gene conversion in our species. We conclude that during recent evolution, an average of approximately 600 nucleotides per newborn male have undergone Y-Y gene conversion, which has had an important role in the evolution of multi-copy testis gene families in the MSY.