Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes

Epidemics of drug-resistant bacteria emerge worldwide, even as resistant strains frequently have reduced fitness compared to their drug-susceptible counterparts. Data from model systems suggest that the fitness cost of antimicrobial resistance can be reduced by compensatory mutations; however, there is limited evidence that compensatory evolution has any significant role in the success of drug-resistant bacteria in human populations. Here we describe a set of compensatory mutations in the RNA polymerase genes of rifampicin-resistant M. tuberculosis, the etiologic agent of human tuberculosis (TB). M. tuberculosis strains harboring these compensatory mutations showed a high competitive fitness in vitro. Moreover, these mutations were associated with high fitness in vivo, as determined by examining their relative clinical frequency across patient populations. Of note, in countries with the world's highest incidence of multidrug-resistant (MDR) TB, more than 30% of MDR clinical isolates had this form of mutation. Our findings support a role for compensatory evolution in the global epidemics of MDR TB.     

Fluorescence detection in automated DNA sequence analysis

We have developed a method for the partial automation of DNA sequence analysis. Fluorescence detection of the DNA fragments is accomplished by means of a fluorophore covalently attached to the oligonucleotide primer used in enzymatic DNA sequence analysis. A different coloured fluorophore is used for each of the reactions specific for the bases A, C, G and T. The reaction mixtures are combined and co-electrophoresed down a single polyacrylamide gel tube, the separated fluorescent bands of DNA are detected near the bottom of the tube, and the sequence information is acquired directly by computer.     

Methane drizzle on Titan

Saturn's moon Titan shows landscapes with fluvial features suggestive of hydrology based on liquid methane. Recent efforts in understanding Titan's methane hydrological cycle have focused on occasional cloud outbursts near the south pole or cloud streaks at southern mid-latitudes and the mechanisms of their formation. It is not known, however, if the clouds produce rain or if there are also non-convective clouds, as predicted by several models. Here we show that the in situ data on the methane concentration and temperature profile in Titan's troposphere point to the presence of layered optically thin stratiform clouds. The data indicate an upper methane ice cloud and a lower, barely visible, liquid methane-nitrogen cloud, with a gap in between. The lower, liquid, cloud produces drizzle that reaches the surface. These non-convective methane clouds are quasi-permanent features supported by the global atmospheric circulation, indicating that methane precipitation occurs wherever there is slow upward motion. This drizzle is a persistent component of Titan's methane hydrological cycle and, by wetting the surface on a global scale, plays an active role in the surface geology of Titan.     

The abundances of constituents of Titan's atmosphere from the GCMS instrument on the Huygens probe

Saturn's largest moon, Titan, remains an enigma, explored only by remote sensing from Earth, and by the Voyager and Cassini spacecraft. The most puzzling aspects include the origin of the molecular nitrogen and methane in its atmosphere, and the mechanism(s) by which methane is maintained in the face of rapid destruction by photolysis. The Huygens probe, launched from the Cassini spacecraft, has made the first direct observations of the satellite's surface and lower atmosphere. Here we report direct atmospheric measurements from the Gas Chromatograph Mass Spectrometer (GCMS), including altitude profiles of the constituents, isotopic ratios and trace species (including organic compounds). The primary constituents were confirmed to be nitrogen and methane. Noble gases other than argon were not detected. The argon includes primordial 36Ar, and the radiogenic isotope 40Ar, providing an important constraint on the outgassing history of Titan. Trace organic species, including cyanogen and ethane, were found in surface measurements.     

Mutations in SDHC cause autosomal dominant paraganglioma, type 3

Nonchromaffin paragangliomas (PGLs) are usually benign, neural-crest-derived, slow-growing tumours of parasympathetic ganglia. Between 10% and 50% of cases are familial and are transmitted as autosomal dominant traits with incomplete and age-dependent penetrance.     

The genome sequence of Atlantic cod reveals a unique immune system

Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes. The major histocompatibility complex (MHC)?II is a conserved feature of the adaptive immune system of jawed vertebrates, but we show that Atlantic cod has lost the genes for MHC?II, CD4 and invariant chain (Ii) that are essential for the function of this pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions. We find a highly expanded number of MHC?I genes and a unique composition of its Toll-like receptor (TLR) families. This indicates how the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC?II. These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates.