SOS response promotes horizontal dissemination of antibiotic resistance genes

Mobile genetic elements have a crucial role in spreading antibiotic resistance genes among bacterial populations. Environmental and genetic factors that regulate conjugative transfer of antibiotic resistance genes in bacterial populations are largely unknown. Integrating conjugative elements (ICEs) are a diverse group of mobile elements that are transferred by means of cell-cell contact and integrate into the chromosome of the new host. SXT is a approximately 100-kilobase ICE derived from Vibrio cholerae that encodes genes that confer resistance to chloramphenicol, sulphamethoxazole, trimethoprim and streptomycin. SXT-related elements were not detected in V. cholerae before 1993 but are now present in almost all clinical V. cholerae isolates from Asia. ICEs related to SXT are also present in several other bacterial species and encode a variety of antibiotic and heavy metal resistance genes. Here we show that SetR, an SXT encoded repressor, represses the expression of activators of SXT transfer. The 'SOS response' to DNA damage alleviates this repression, increasing the expression of genes necessary for SXT transfer and hence the frequency of transfer. SOS is induced by a variety of environmental factors and antibiotics, for example ciprofloxacin, and we show that ciprofloxacin induces SXT transfer as well. Thus, we present a mechanism by which therapeutic agents can promote the spread of antibiotic resistance genes.     

Gene flow maintains a large genetic difference in clutch size at a small spatial scale

Understanding the capacity of natural populations to adapt to their local environment is a central topic in evolutionary biology. Phenotypic differences between populations may have a genetic basis, but showing that they reflect different adaptive optima requires the quantification of both gene flow and selection. Good empirical data are rare. Using data on a spatially structured island population of great tits (Parus major), we show here that a persistent difference in mean clutch size between two subpopulations only a few kilometres apart has a major genetic component. We also show that immigrants from outside the island carry genes for large clutches. But gene flow into one subpopulation is low, as a result of a low immigration rate together with strong selection against immigrant genes. This has allowed for adaptation to the island environment and the maintenance of small clutches. In the other area, however, higher gene flow prevents local adaptation and maintains larger clutches. We show that the observed small-scale genetic difference in clutch size is not due to divergent selection on the island, but to different levels of gene flow from outside the island. Our findings illustrate the large effect of immigration on the evolution of local adaptations and on genetic population structure.     

Identification of two genes causing reinforcement in the Texas wildflower Phlox drummondii

Species formation generates biological diversity and occurs when traits evolve that prevent gene flow between populations. Discerning the number and distribution of genes underlying these traits and, in a few cases, identifying the genes involved, has greatly enhanced our understanding over the past 15 years of species formation (reviewed by Noor and Feder and Wolf et al.). However, this work has almost exclusively focused on traits that restrict gene flow between populations that have evolved as a by-product of genetic divergence between geographically isolated populations. By contrast, little is known about the characteristics of genes associated with reinforcement, the process by which natural selection directly favours restricted gene flow during the formation of species. Here we identify changes in two genes that appear to cause a flower colour change in Phlox drummondii, which previous work has shown contributes to reinforcement. Both changes involve cis-regulatory mutations to genes in the anthocyanin biosynthetic pathway (ABP). Because one change is recessive whereas the other is dominant, hybrid offspring produce an intermediate flower colour that is visited less by pollinators, and is presumably maladaptive. Thus genetic change selected to increase prezygotic isolation also appears to result in increased postzygotic isolation.     

Development of specific chromosomal DNA pool for rice field eel and their application to gene mapping

The chromosomes 1, 3, 5, 6, 7, 10 and 12 of rice field eel (Monopterus albus Zuiew) have been microdissected successfully from meiosis Ⅰ diakinesis spreads by using glass microneedle under an inverted microscope. And the DOP-PCR products of the single chromosome dotted on the nylon membrane as “specific chromosomal DNA pool”, have been hybridized with 6 probes to map these genes. The mapping results show that Zfa has been mapped to chromosome 1, rDNA to chromosomes 3 and 7, both Gh and Pdegg to chromosome 10, Hsl to chromosome 5 and Hox genes have been detected on chromosomes 1, 3, 6 and 10 meantime. It has initiatively been suggested that chromosome 10 of rice field eel might possess the commom conserved synteny to that on chromosome 17 of human, chromosome 11 of mouse, chromosome 12 of pig and chromosome 19 of bovine. And so chromosome 3 of rice field eel might also contain the commom conserved synteny to that on chromosome 2 of zebrafish. Our study is an attempt to establish a new and feasible method to advance the study of gene mapping and chromosome evolution in fish, and also to provide a new idea to distinguish each chromosome on the base of molecular markers for fish.     

Stability of expression-linked surface antigen gene in Trypanosoma equiperdum

African trypanosomes evade clearance in immune-competent hosts by periodically replacing their major surface glycoprotein with an antigenically different glycoprotein. Expression of many of these variant surface glycoproteins (VSGs) is associated with the duplication and transposition of silent basic copy genes (BCs) into unlinked genomic expression sites. The new expression-linked VSG gene copies (ELCs) are oriented with their 3' ends proximal to chromosome telomeres. Other VSG genes are activated without the production of an ELC. The 3' ends of these VSG genes are near chromosome telomeres both when they are active and when they are inactive. Recently, we have shown that activation of the VSG-1 gene in the BoTaR (Bordeaux trypanozoon antigen repertoire) serodeme of Trypanosoma equiperdum involves the duplication and transposition of a telomeric BC gene into one of at least three unlinked telomeric sites. Here we show that the VSG-1 ELC is inactivated but not eliminated in some antigenic variants derived from a VSG-1 expressor. In addition, a subsequent variant that again expresses VSG-1 has not reactivated the residual VSG-1 ELC (R-ELC), but instead contains a new, active VSG-1 ELC in an unlinked telomeric site. These results show that the simple presence of an ELC in a potential expression site is not sufficient for its expression.     

Mating patterns in seminatural populations of mice influenced by MHC genotype

Because of the central role of major histocompatibility complex (MHC) genes in immune recognition, it is often assumed that parasite-driven selection maintains the unprecendented genetic diversity of these genes. But associations between MHC genotype and specific infectious diseases have been difficult to identify with a few exceptions such as Marek's disease and malaria. Alternatively, MHC-related reproductive mechanisms such as selective abortion and mating preferences could be responsible for the diversity. To determine both the nature and strength of selection operating on MHC genes by we have studied components of selection in seminatural populations of mice (Mus musculus domesticus). Here we assess MHC-related patterns of reproduction and early (preweaning) mortality by analysing 1,139 progeny born in nine populations, and 662 progeny from laboratory matings. Reproductive mechanisms, primarily mating preferences, result in 27% fewer MHC-homozygous offspring than expected from random mating. MHC genotype had no detectable influence on neonatal (preweaning) mortality. These mating preferences are strong enough to account for most of the MHC genetic diversity found in natural populations of Mus.     

DNA sequence and comparative analysis of chimpanzee chromosome 22

Human-chimpanzee comparative genome research is essential for narrowing down genetic changes involved in the acquisition of unique human features, such as highly developed cognitive functions, bipedalism or the use of complex language. Here, we report the high-quality DNA sequence of 33.3 megabases of chimpanzee chromosome 22. By comparing the whole sequence with the human counterpart, chromosome 21, we found that 1.44% of the chromosome consists of single-base substitutions in addition to nearly 68,000 insertions or deletions. These differences are sufficient to generate changes in most of the proteins. Indeed, 83% of the 231 coding sequences, including functionally important genes, show differences at the amino acid sequence level. Furthermore, we demonstrate different expansion of particular subfamilies of retrotransposons between the lineages, suggesting different impacts of retrotranspositions on human and chimpanzee evolution. The genomic changes after speciation and their biological consequences seem more complex than originally hypothesized.     

The genome sequence and structure of rice chromosome 1

The rice species Oryza sativa is considered to be a model plant because of its small genome size, extensive genetic map, relative ease of transformation and synteny with other cereal crops. Here we report the essentially complete sequence of chromosome 1, the longest chromosome in the rice genome. We summarize characteristics of the chromosome structure and the biological insight gained from the sequence. The analysis of 43.3 megabases (Mb) of non-overlapping sequence reveals 6,756 protein coding genes, of which 3,161 show homology to proteins of Arabidopsis thaliana, another model plant. About 30% (2,073) of the genes have been functionally categorized. Rice chromosome 1 is (G + C)-rich, especially in its coding regions, and is characterized by several gene families that are dispersed or arranged in tandem repeats. Comparison with a draft sequence indicates the importance of a high-quality finished sequence.     

A second generation human haplotype map of over 3.1 million SNPs

We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r2 of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r2 of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations.     

Hedgehog signalling controls eye degeneration in blind cavefish

Hedgehog (Hh) proteins are responsible for critical signalling events during development but their evolutionary roles remain to be determined. Here we show that hh gene expression at the embryonic midline controls eye degeneration in blind cavefish. We use the teleost Astyanax mexicanus, a single species with an eyed surface-dwelling form (surface fish) and many blind cave forms (cavefish), to study the evolution of eye degeneration. Small eye primordia are formed during cavefish embryogenesis, which later arrest in development, degenerate and sink into the orbits. Eye degeneration is caused by apoptosis of the embryonic lens, and transplanting a surface fish embryonic lens into a cavefish optic cup can restore a complete eye. Here we show that sonic hedgehog (shh) and tiggy-winkle hedgehog (twhh) gene expression is expanded along the anterior embryonic midline in several different cavefish populations. The expansion of hh signalling results in hyperactivation of downstream genes, lens apoptosis and arrested eye growth and development. These features can be mimicked in surface fish by twhh and/or shh overexpression, supporting the role of hh signalling in the evolution of cavefish eye regression.     

The medaka draft genome and insights into vertebrate genome evolution

Teleosts comprise more than half of all vertebrate species and have adapted to a variety of marine and freshwater habitats. Their genome evolution and diversification are important subjects for the understanding of vertebrate evolution. Although draft genome sequences of two pufferfishes have been published, analysis of more fish genomes is desirable. Here we report a high-quality draft genome sequence of a small egg-laying freshwater teleost, medaka (Oryzias latipes). Medaka is native to East Asia and an excellent model system for a wide range of biology, including ecotoxicology, carcinogenesis, sex determination and developmental genetics. In the assembled medaka genome (700 megabases), which is less than half of the zebrafish genome, we predicted 20,141 genes, including approximately 2,900 new genes, using 5'-end serial analysis of gene expression tag information. We found single nucleotide polymorphisms (SNPs) at an average rate of 3.42% between the two inbred strains derived from two regional populations; this is the highest SNP rate seen in any vertebrate species. Analyses based on the dense SNP information show a strict genetic separation of 4 million years (Myr) between the two populations, and suggest that differential selective pressures acted on specific gene categories. Four-way comparisons with the human, pufferfish (Tetraodon), zebrafish and medaka genomes revealed that eight major interchromosomal rearrangements took place in a remarkably short period of approximately 50 Myr after the whole-genome duplication event in the teleost ancestor and afterwards, intriguingly, the medaka genome preserved its ancestral karyotype for more than 300 Myr.     

Genetic analysis of autoimmune type 1 diabetes mellitus in mice.

Two genes, Idd-3 and Idd-4, that influence the onset of autoimmune type 1 diabetes in the nonobese diabetic mouse have been located on chromosomes 3 and 11, outside the chromosome 17 major histocompatibility complex. A genetic map of the mouse genome, analysed using the polymerase chain reaction, has been assembled specifically for the study. On the basis of comparative maps of the mouse and human genomes, the homologue of Idd-3 may reside on human chromosomes 1 or 4 and Idd-4 on chromosome 17.     

Demasculinization of X chromosomes in the Drosophila genus

X chromosomes evolve differently from autosomes, but general governing principles have not emerged. For example, genes with male-biased expression are under-represented on the X chromosome of D. melanogaster, but are randomly distributed in the genome of Anopheles gambiae. In direct global profiling experiments using species-specific microarrays, we find a nearly identical paucity of genes with male-biased expression on D. melanogaster, D. simulans, D. yakuba, D. ananassae, D. virilis and D. mojavensis X chromosomes. We observe the same under-representation on the neo-X of D. pseudoobscura. It has been suggested that precocious meiotic silencing of the X chromosome accounts for reduced X chromosome male-biased expression in nematodes, mammals and Drosophila. We show that X chromosome genes with male-biased expression are under-represented in somatic cells and in mitotic male germ cells. These data are incompatible with simple X chromosome inactivation models. Using expression profiling and comparative sequence analysis, we show that selective gene extinction on the X chromosome, creation of new genes on autosomes and changed genomic location of existing genes contribute to the unusual X chromosome gene content.     

Female sticklebacks count alleles in a strategy of sexual selection explaining MHC polymorphism.

The origin and maintenance of polymorphism in major histocompatibility complex (MHC) genes in natural populations is still unresolved. Sexual selection, frequency-dependent selection by parasites and pathogens, and heterozygote advantage have been suggested to explain the maintenance of high allele diversity at MHC genes. Here we argue that there are two (non-exclusive) strategies for MHC-related sexual selection, representing solutions to two different problems: inbreeding avoidance and parasite resistance. In species prone to inadvertent inbreeding, partners should prefer dissimilar MHC genotypes to similar ones. But if the goal is to maximize the resistance of offspring towards potential infections, the choosing sex should prefer mates with a higher diversity of MHC alleles. This latter strategy should apply when there are several MHC loci, as is the case in most vertebrates. We tested the relative importance of an 'allele counting' strategy compared to a disassortative mating strategy using wild-caught three-spined sticklebacks (Gasterosteus aculeatus) from an interconnected system of lakes. Here we show that gravid female fish preferred the odour of males with a large number of MHC class-IIB alleles to that of males with fewer alleles. Females did not prefer male genotypes dissimilar to their own.     

Evolutionary diversification of TTX-resistant sodium channels in a predator-prey interaction

Understanding the molecular genetic basis of adaptations provides incomparable insight into the genetic mechanisms by which evolutionary diversification takes place. Whether the evolution of common traits in different lineages proceeds by similar or unique mutations, and the degree to which phenotypic evolution is controlled by changes in gene regulation as opposed to gene function, are fundamental questions in evolutionary biology that require such an understanding of genetic mechanisms. Here we identify novel changes in the molecular structure of a sodium channel expressed in snake skeletal muscle, tsNa(V)1.4, that are responsible for differences in tetrodotoxin (TTX) resistance among garter snake populations coevolving with toxic newts. By the functional expression of tsNa(V)1.4, we show how differences in the amino-acid sequence of the channel affect TTX binding and impart different levels of resistance in four snake populations. These results indicate that the evolution of a physiological trait has occurred through a series of unique functional changes in a gene that is otherwise highly conserved among vertebrates.     

Human genes for U2 small nuclear RNA map to a major adenovirus 12 modification site on chromosome 17

U2 RNA is one of the abundant, highly conserved species of small nuclear RNA (snRNA) molecules implicated in RNA processing. As is typical of mammalian snRNAs, human U1 and U2 are each encoded by a multigene family. In the human genome, defective copies of the genes (pseudogenes) far outnumber the authentic genes. The majority or all of the 35 to 100 bona fide U1 genes have at least 20 kilobases (kb) of nearly perfect 5' and 3' flanking homology in common with each other; these U1 genes are clustered loosely in chromosome band 1p36 (refs 5, 7) with intergenic distances exceeding 44 kb. In contrast, the 10 to 20 U2 genes are clustered tightly in a virtually perfect tandem array which has a strict 6-kb repeating unit. We report here the assignment, by in situ hybridization, of the U2 gene cluster to chromosome 17, bands q21-q22. Surprisingly, this region is one of three major adenovirus 12 modification sites which undergo chromosome decondensation ('uncoiling') in permissive human cells infected by highly oncogenic strains of adenovirus. The two other major modification sites, 1p36 and 1q21, coincide with the locations of U1 genes and class I U1 pseudogenes, respectively. We suggest that snRNA genes are the major targets of viral chromosome modification.     

Identification and mapping to chromosome 1 of a susceptibility locus for periinsulitis in non-obese diabetic mice

Insulin-dependent diabetes mellitus (IDDM) is a polygenic disease caused by autoimmune destruction of insulin-producing beta cells in the islets of Langerhans. Its onset is preceded by a long and variable period in which lymphoid cells infiltrate the pancreas but first remain outside the islets (peri-insulitis) before invading them (insulitis). Among susceptibility loci, only the major histocompatibility complex (MHC) has been clearly assigned. Genetic study of the nonobese diabetic (NOD) mouse model for insulin-dependent diabetes mellitus has revealed genetic linkage of insulitis and of early onset diabetes with two non-MHC loci mapping to chromosome 3 and 11 respectively. Here we report a close association of periinsulitis with a third non-MHC locus mapping to chromosome 1. Successive stages in the progression of diabetic disease thus appear to be controlled by distinct genes or sets of genes.