The effects of mispair and nonpair correction in hybrid DNA on base ratios (G + C content) and total amounts of DNA

Base ratios and total DNA amounts can vary substantially between and within higher taxa and genera, and even within species. Gene conversion is one of several mechanisms that could cause such changes. For base substitutions, disparity in conversion direction is accompanied by an equivalent disparity in base ratio at the heterozygous site. Disparity in the direction of gene conversion at meiosis is common and can be extreme. For transitions (which give purine [R]/pyrimidine [Y] mispairs) and for transversions giving unlike R/R and Y/Y mispairs in hybrid DNA, this disparity could give slow but systematic changes in G + C percentage. For transversions giving like R/R and Y/Y mispairs, it could change AT/TA and CG/GC ratios. From the extent of correction direction disparity, one can deduce properties of repair enzymes, such as the ability (1) to excise preferentially the purine from one mispair and the pyrimidine from the other for two different R/Y mispairs from a single heterozygous site and (2) to excise one base preferentially from unlike R/R or Y/Y mispairs. Frame-shifts usually show strong disparity in conversion direction, with preferential cutting of the nonlooped or the looped-out strand of the nonpair in heterozygous h-DNA. The opposite directions of disparity for frame-shifts and their intragenic suppressors as Ascobolus suggest that repair enzymes have a strong, systematic bias as to which strand is cut. The conversion spectra of mutations induced with different mutagens suggest that the nonlooped strand is preferentially cut, so that base additions generally convert to mutant and deletions generally convert to wild-type forms. Especially in nonfunctional or noncoding DNA, this could cause a general increase in DNA amounts. Conversion disparity, selection, mutation, and other processes interact, affecting rates of change in base ratios and total DNA.      

Comparison of historical bottleneck effects and genetic consequences of re‐introduction in a critically endangered island passerine

Re‐introduction is an important tool for recovering endangered species; however, the magnitude of genetic consequences for re‐introduced populations remains largely unknown, in particular the relative impacts of historical population bottlenecks compared to those induced by conservation management. We characterize 14 microsatellite loci developed for the Seychelles paradise flycatcher and use them to quantify temporal and spatial measures of genetic variation across a 134‐year time frame encompassing a historical bottleneck that reduced the species to ~28 individuals in the 1960s, through the initial stages of recovery and across a second contemporary conservation‐introduction‐induced bottleneck. We then evaluate the relative impacts of the two bottlenecks, and finally apply our findings to inform broader re‐introduction strategy. We find a temporal trend of significant decrease in standard measures of genetic diversity across the historical bottleneck, but only a nonsignificant downward trend in number of alleles across the contemporary bottleneck. However, accounting for the different timescales of the two bottlenecks (~40 historical generations versus <1 contemporary generation), the loss of genetic diversity per generation is greater across the contemporary bottleneck. Historically, the flycatcher population was genetically structured; however, extinction on four of five islands has resulted in a homogeneous contemporary population. We conclude that severe historical bottlenecks can leave a large footprint in terms of sheer quantity of genetic diversity lost. However, severely depleted genetic diversity does not render a species immune to further genetic erosion upon re‐introduction. In some cases, the loss of genetic diversity per generation can, initially at least, be greater across re‐introduction‐induced bottlenecks.     

MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake

The Staphylococcus aureus DtxR-like protein, MntR, controls expression of the mntABC and mntH genes, which encode putative manganese transporters. Mutation of mntABC produced a growth defect in metal-depleted medium and increased sensitivity to intracellularly generated superoxide radicals. These phenotypes resulted from diminished uptake of manganese and were rescued by the addition of excess Mn(II). Resistance to superoxide was incompletely rescued by Mn(II) for STE035 (mntA mntH), and the strain had reduced virulence in a murine abscess model of infection. Expression of mntABC was repressed by Mn(II) in an MntR-dependent manner, which contrasts with the expression of mntH that was not repressed in elevated Mn(II) and was decreased in an mntR mutant. This demonstrates that MntR acts as a negative and positive regulator of these loci respectively. PerR, the peroxide resistance regulon repressor, acts with MntR to control the expression of mntABC and manganese uptake. The expression of the PerR-regulated genes, katA (catalase), ftn (ferritin) and fur (ferric uptake regulator), was diminished in STE031 (mntR) when grown in excess Mn(II). Therefore, the control of Mn(II)-regulated members of the PerR regulon and the Fur protein is modulated by MntR through its control of Mn(II) uptake. The co-ordinated regulation of metal ion homeostasis and oxidative stress resistance via the regulators MntR, PerR and Fur of S. aureus is discussed.     

A Century of Tuberculosis Epidemiology in the Northern and Southern Hemisphere: The Differential Impact of Control Interventions

Background

Cape Town has one of the highest TB burdens of any city in the world. In 1900 the City of Cape Town, New York City and London had high mortality of tuberculosis (TB). Throughout the 20th century contemporaneous public health measures including screening, diagnosis and treatment were implemented in all three settings. Mandatory notification of TB and vital status enabled comparison of disease burden trajectories.

Methods

TB mortality, notification and case fatality rates were calculated from 1912 to 2012 using annual TB notifications, TB death certifications and population estimates. Notification rates were stratified by age and in Cape Town by HIV status (from 2009 onwards).

Results

Pre-chemotherapy, TB mortality and notification rates declined steadily in New York and London but remained high in Cape Town. Following introduction of combination chemotherapy, mean annual case fatality dropped from 45–60% to below 10% in all three settings. Mortality and notification rates subsequently declined, although Cape Town notifications did not decline as far as those in New York or London and returned to pre-chemotherapy levels by 1980. The proportional contribution of childhood TB diminished in New York and London but remained high in Cape Town. The advent of the Cape Town HIV-epidemic in the 1990s was associated with a further two-fold increase in incidence. In 2012, notification rates among HIV-negatives remained at pre-chemotherapy levels.

Conclusions

TB control was achieved in New York and London but failed in Cape Town. The TB disease burden trajectories started diverging before the availability of combination chemotherapy in 1952 and further diverged following the HIV epidemic in 1990. Chemotherapy impacted case fatality but not transmission, evidenced by on-going high childhood TB rates. Currently endemic TB results from high on-going transmission, which has been exacerbated by the HIV epidemic. TB control will require reducing transmission, which is inexorably linked to prevailing socio-economic factors.     

Conservation by trans-border cooperation: population genetic structure and diversity of geoffroy’s bat (Myotis emarginatus) at its north-western european range edge

Biodiversity and Conservation - In the European Union, all bat species are strictly protected and member states must ensure their conservation. However, if populations are genetically structured,...     

AcmA of Lactococcus lactis is an N-acetylglucosaminidase with an optimal number of LysM domains for proper functioning

AcmA, the major autolysin of Lactococcus lactis MG1363 is a modular protein consisting of an N-terminal active site domain and a C-terminal peptidoglycan-binding domain. The active site domain is homologous to that of muramidase-2 of Enterococcus hirae, however, RP-HPLC analysis of muropeptides released from Bacillus subtilis peptidoglycan, after digestion with AcmA, shows that AcmA is an N-acetylglucosaminidase. In the C-terminus of AcmA three highly similar repeated regions of 45 amino acid residues are present, which are separated by short nonhomologous sequences. The repeats of AcmA, which belong to the lysine motif (LysM) domain family, were consecutively deleted, removed, or, alternatively, one additional repeat was added, without destroying the cell wall-hydrolyzing activity of the enzyme in vitro, although AcmA activity was reduced in all cases. In vivo, proteins containing no or only one repeat did not give rise to autolysis of lactococcal cells, whereas separation of the producer cells from the chains was incomplete. Exogenously added AcmA deletion derivatives carrying two repeats or four repeats bound to lactococcal cells, whereas the derivative with no or one repeat did not. In conclusion, these results show that AcmA needs three LysM domains for optimal peptidoglycan binding and biological functioning.     

The evolution and maintenance of virulence in Staphylococcus aureus: a role for host-to-host transmission?

Despite progress in our understanding of infectious disease biology and prevention, the conditions that select for the establishment and maintenance of microbial virulence remain enigmatic. To address this aspect of pathogen biology, we focus on two members of the Staphylococcus genus - Staphylococcus aureus and Staphylococcus epidermidis - and consider why S. aureus has evolved to become more virulent than S. epidermidis. Several hypotheses to explain this phenomenon are discussed and a mathematical model is used to argue that a complex transmission pathway is the key factor in explaining the evolution and maintenance of virulence in S. aureus. In the case of S. epidermidis, where skin contact affords easier transmission between hosts, high levels of virulence do not offer an advantage to this pathogen.