Major effect of retinal short-chain dehydrogenase reductase (RDHE2) on bovine fat colour

Beef with yellow fat is considered undesirable by consumers in most European and Asian markets. β-Carotene is the major carotenoid deposited in the adipose tissue and milk fat of cattle (Bos taurus), which can result in the yellowness. The effects of retinal short-chain dehydrogenase reductase (RDHE2) and β, β-carotene 9',10-dioxygenase (BCO2) were considered jointly as major candidate genes for causing the yellow fat colour, based on their genomic locations in the fat colour quantitative trait loci (QTL) and their roles in the metabolism of β-carotene. In a secondary pathway, BCO2 cleaves β-carotene into retinoic acid, the most potent form of vitamin A. RDHE2 converts trans-retinol to trans-retinal, a less active form of vitamin A. We evaluated the effects of two amino acid variants of the RDHE2 gene (V6A and V33A) along with a mutation in the BCO2 gene that results in a stop codon (W80X) in seven cattle populations. The RDHE2 V6A genotype affected several fat colour traits but the size of the effect varied in the populations studied. The genotype effect of the RDHE2 V33A variant was observed only in New Zealand samples of unknown breed. In general, the individual effects of RDHE2 V6A and V33A SNPs genotypes were greater in the random New Zealand samples than in samples from pedigreed Jersey-Limousin backcross progeny, accounting for 8-17 % of the variance in one population. Epistasis between the BCO2 W80X and RDHE2 variants was observed, and in some populations this explained more of the variation than the effects of the individual RDHE2 variants.     

Quantifying the impact of dependent evolution among sites in phylogenetic inference

Nearly all commonly used methods of phylogenetic inference assume that characters in an alignment evolve independently of one another. This assumption is attractive for simplicity and computational tractability but is not biologically reasonable for RNAs and proteins that have secondary and tertiary structures. Here, we simulate RNA and protein-coding DNA sequence data under a general model of dependence in order to assess the robustness of traditional methods of phylogenetic inference to violation of the assumption of independence among sites. We find that the accuracy of independence-assuming methods is reduced by the dependence among sites; for proteins this reduction is relatively mild, but for RNA this reduction may be substantial. We introduce the concept of effective sequence length and its utility for considering information content in phylogenetics.     

Quantifying the Contribution of Statins to the Decline in Population Mean Cholesterol by Socioeconomic Group in England 1991 - 2012: A Modelling Study

Background

Serum total cholesterol is one of the major targets for cardiovascular disease prevention. Statins are effective for cholesterol control in individual patients. At the population level, however, their contribution to total cholesterol decline remains unclear. The aim of this study was to quantify the contribution of statins to the observed fall in population mean cholesterol levels in England over the past two decades, and explore any differences between socioeconomic groups.

Methods and Findings

This is a modelling study based on data from the Health Survey for England. We analysed changes in observed mean total cholesterol levels in the adult England population between 1991-92 (baseline) and 2011-12. We then compared the observed changes with a counterfactual ‘no statins’ scenario, where the impact of statins on population total cholesterol was estimated and removed. We estimated uncertainty intervals (UI) using Monte Carlo simulation, where confidence intervals (CI) were impractical. In 2011-12, 13.2% (95% CI: 12.5-14.0%) of the English adult population used statins at least once per week, compared with 1991-92 when the proportion was just 0.5% (95% CI: 0.3-1.0%). Between 1991-92 and 2011-12, mean total cholesterol declined from 5.86 mmol/L (95% CI: 5.82-5.90) to 5.17 mmol/L (95% CI: 5.14-5.20). For 2011-12, mean total cholesterol was lower in more deprived groups. In our ‘no statins’ scenario we predicted a mean total cholesterol of 5.36 mmol/L (95% CI: 5.33-5.40) for 2011-12. Statins were responsible for approximately 33.7% (95% UI: 28.9-38.8%) of the total cholesterol reduction since 1991-92. The statin contribution to cholesterol reduction was greater among the more deprived groups of women, while showing little socio-economic gradient among men.

Conclusions

Our model suggests that statins explained around a third of the substantial falls in total cholesterol observed in England since 1991. Approximately two thirds of the cholesterol decrease can reasonably be attributed non-pharmacological determinants.     

Repeated horizontal gene transfer of GALactose metabolism genes violates Dollo’s law of irreversible loss

Dollo’s law posits that evolutionary losses are irreversible, thereby narrowing the potential paths of evolutionary change. While phenotypic reversals to ancestral states have been observed, little is known about their underlying genetic causes. The genomes of budding yeasts have been shaped by extensive reductive evolution, such as reduced genome sizes and the losses of metabolic capabilities. However, the extent and mechanisms of trait reacquisition after gene loss in yeasts have not been thoroughly studied. Here, through phylogenomic analyses, we reconstructed the evolutionary history of the yeast galactose utilization pathway and observed widespread and repeated losses of the ability to utilize galactose, which occurred concurrently with the losses of GALactose (GAL) utilization genes. Unexpectedly, we detected multiple galactose-utilizing lineages that were deeply embedded within clades that underwent ancient losses of galactose utilization. We show that at least two, and possibly three, lineages reacquired the GAL pathway via yeast-to-yeast horizontal gene transfer. Our results show how trait reacquisition can occur tens of millions of years after an initial loss via horizontal gene transfer from distant relatives. These findings demonstrate that the losses of complex traits and even whole pathways are not always evolutionary dead-ends, highlighting how reversals to ancestral states can occur.     

Molecular assays for detecting Aphanomyces invadans in ulcerative mycotic fish lesions

The pathogenic oomycete Aphanomyces invadans is the primary etiological agent in ulcerative mycosis, an ulcerative skin disease caused by a fungus-like agent of wild and cultured fish. We developed sensitive PCR and fluorescent peptide nucleic acid in situ hybridization (FISH) assays to detect A. invadans. Laboratory-challenged killifish (Fundulus heteroclitus) were first tested to optimize and validate the assays. Skin ulcers of Atlantic menhaden (Brevoortia tyrannus) from populations found in the Pamlico and Neuse River estuaries in North Carolina were then surveyed. Results from both assays indicated that all of the lesioned menhaden (n = 50) collected in September 2004 were positive for A. invadans. Neither the FISH assay nor the PCR assay cross-reacted with other closely related oomycetes. These results provided strong evidence that A. invadans is the primary oomycete pathogen in ulcerative mycosis and demonstrated the utility of the assays. The FISH assay is the first molecular assay to provide unambiguous visual confirmation that hyphae in the ulcerated lesions were exclusively A. invadans.     

Efficacy model for antibody-mediated pre-erythrocytic malaria vaccines

Antibodies to the pre-erythrocytic antigens, circumsporozoite protein (CSP), thrombospondin-related adhesive protein (TRAP) and liver-stage antigen 1, have been measured in field studies of semi-immune adults and shown to correlate with protection from Plasmodium falciparum infection. A mathematical model is formulated to estimate the probability of sporozoite infection as a function of antibody titres to multiple pre-erythrocytic antigens. The variation in antibody titres from field data was used to estimate the relationship between the probability of P. falciparum infection per infectious mosquito bite and antibody titre. Using this relationship, we predict the effect of vaccinations that boost baseline CSP or TRAP antibody titres. Assuming the estimated relationship applies to vaccine-induced antibody titres, then single-component CSP or TRAP antibody-mediated pre-erythrocytic vaccines are likely to provide partial protection from infection, with vaccine efficacy of approximately 50 per cent depending on the magnitude of the vaccine-induced boost to antibody titres. It is possible that the addition of a TRAP component to a CSP-based vaccine such as RTS,S would provide an increase in infection-blocking efficacy of approximately 25 per cent should the problem of immunological interference between antigens be overcome.