Mortality and birth weight in Philadelphia Blacks: an example of stabilizing selection

It has been suggested that as a result of the action of natural selection the mean value of any biological measurement would be the most normal value and associated with the most favorable survival rate. Selection is said to be stabilizing (or normalizing or balancing) if individuals with intermediate values for a given quantitative trait have the highest fitness. Birth weight is perhaps the most clear-cut example of a human character subject to stabilizing selection. This paper presents the distribution of birth weights among 8382 Philadelphia Black infants and the rate of perinatal mortality for the birth weight classes. Using these data, several analyses of stabilizing selection are made. The data were taken from the Collaborative Study on Cerebral Palsy, Mental Retardation, and other Neurological and Sensory Disorders of Infancy and Childhood.     

The SNPs of Melanocortin 4 Receptor (MC4R) Associated with Body Weight in Beagle Dogs

Melanocortin 4 receptor (MC4R), which is associated with inherited human obesity, is involoved in food intake and body weight of mammals. To study the relationships between MC4R gene polymorphism and body weight in Beagle dogs, we detected and compared the nucleotide sequence of the whole coding region and 3′- and 5′- flanking regions of the dog MC4R gene (1214 bp). In 120 Beagle dogs, two SNPs (A420C, C895T) were identified and their relation with body weight was analyzed with RFLP-PCR method. The results showed that the SNP at A420C was significantly associated with canine body weight trait when it changed amino acid 101 of the MC4R protein from asparagine to threonine,while canine body weight variations were significant in female dogs when MC4R nonsense mutation at C895T. It suggested that the two SNPs might affect the MC4R gene’s function which was relative to body weight in Beagle dogs. Therefore, MC4R was a candidate gene for selecting different size dogs with the MC4R SNPs (A420C, C895T) being potentially valuable as a genetic marker.     

A weight of evidence approach for selecting exposure biomarkers for biomonitoring

Context: It is known that there are usually several biomarkers and/or medium combinations that can be applied to answer a specific exposure question. To help determine an appropriate combination for the specific question, we have developed a weight-of-evidence Framework that provides a relative appropriateness score for competing combinations.

Methods: The Framework is based on an expert assessor’s evaluation of the relevance and suitability of the biomarker and medium for the question based on a set of criteria. We provide a computer based modeling tool to guide the researcher through the process.

Results: We present an example with six biomarkers of benzene exposure in one matrix; the six are either the most commonly used biomarkers and/or have recent widespread usage. The example clearly demonstrates the usefulness of the Framework for scoring the choices, as well as the transparency of the method that provides the basis for discussion.

Conclusions: The Framework provides for the first time a method to transparently document the rationale behind selecting, from among a set of alternatives, the most scientifically supportable exposure biomarker to address a specific biomonitoring question, thus providing a reproducible account of expert opinions on the suitability of a biomarker.     

Barley γ3-hordein: Glycosylation at an atypical site,disulfide bridge analysis,and reactivity with IgE from patients allergic to wheat

Post translational modifications of a seed storage protein, barley γ3-hordein, were determined using immunochemical and mass spectrometry methods. IgE reactivity towards this protein was measured using sera from patients diagnosed with allergies to wheat. N-glycosylation was found at an atypical Asn-Leu-Cys site. The observed glycan contains xylose. This indicates that at least some γ3-hordein molecules trafficked through the Golgi apparatus. Disulfide bridges in native γ3-hordein were almost the same as those found in wheat γ46-gliadin, except the bridge involving the cysteine included in the glycosylation site. IgE reacted more strongly towards the recombinant than the natural γ3-hordein protein. IgE binding to γ3-hordein increased when the protein sample was reduced. Glycosylation and disulfide bridges therefore decrease epitope accessibility. Thus the IgE from patients sensitized to wheat cross-react with γ3-hordein due to sequence homology with wheat allergens rather than through shared carbohydrate determinants.     

An Optimized Proteomics Approach Reveals Novel Alternative Proteins in Mouse Liver Development

Alternative ORFs (AltORFs) are unannotated sequences in genome that encode novel peptides or proteins named alternative proteins (AltProts). Although ribosome profiling and bioinformatics predict a large number of AltProts, mass spectrometry as the only direct way of identification is hampered by the short lengths and relative low abundance of AltProts. There is an urgent need for improvement of mass spectrometry methodologies for AltProt identification. Here, we report an approach based on size-exclusion chromatography for simultaneous enrichment and fractionation of AltProts from complex proteome. This method greatly simplifies the variance of AltProts discovery by enriching small proteins smaller than 40 kDa. In a systematic comparison between 10 methods, the approach we reported enabled the discovery of more AltProts with overall higher intensities, with less cost of time and effort compared to other workflows. We applied this approach to identify 89 novel AltProts from mouse liver, 39 of which were differentially expressed between embryonic and adult mice. During embryonic development, the upregulated AltProts were mainly involved in biological pathways on RNA splicing and processing, whereas the AltProts involved in metabolisms were more active in adult livers. Our study not only provides an effective approach for identifying AltProts but also novel AltProts that are potentially important in developmental biology.     

Weight Change in Adult Life and Health Outcomes

Objective: To investigate the relationship between weight change in adult life and subsequent mortality and cancer incidence in women. Research Methods and Procedures: In 1994 to 1995, all women (age range, 42 to 81) still under general practitioner observation in the United Kingdom's Royal College of General Practitioners Oral Contraception Study (n = 12 303) were sent a health survey asking about health and lifestyle issues, including current weight and weight at age 30. The main outcome measures were 6‐year all‐cause mortality and cancer incidence among different weight change deciles. Cox regression was used to calculate hazard ratios that were adjusted for: social class at recruitment, BMI at age 30, and age group, parity, smoking status, and hormone replacement therapy status in 1995. Results: Women who had been obese at age 30 were more likely to die and significantly more likely to develop cancer in the 6 years after the health survey than non‐obese respondents. Women reporting weight gains between age 30 and 1995 were significantly less likely to die during the 6 years after the health survey than those with a stable weight, whereas those with weight loss did not fare any better than those in the stable‐weight group. Discussion: Although obesity at young age was associated with subsequent mortality and cancer incidence, weight gain over a time period of 12 to 51 years appeared to be beneficial when compared with women with stable weight over the same time period. Further research is needed to confirm or refute our findings and to allow detailed examination of potential explanations for them.     

Morphological variation associated with dispersal capacity in a tree‐killing bark beetle Dendroctonus ponderosae Hopkins

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Comparative population genomics identified genomic regions and candidate genes associated with fruit domestication traits in peach

Crop evolution is a long‐term process involving selection by natural evolutionary forces and anthropogenic influences; however, the genetic mechanisms underlying the domestication and improvement of fruit crops have not been well studied to date. Here, we performed a population structure analysis in peach (Prunus persica) based on the genome‐wide resequencing of 418 accessions and confirmed the presence of an obvious domestication event during evolution. We identified 132 and 106 selective sweeps associated with domestication and improvement, respectively. Analysis of their tissue‐specific expression patterns indicated that the up‐regulation of selection genes during domestication occurred mostly in fruit and seeds as opposed to other organs. However, during the improvement stage, more up‐regulated selection genes were identified in leaves and seeds than in the other organs. Genome‐wide association studies (GWAS) using 4.24 million single nucleotide polymorphisms (SNPs) revealed 171 loci associated with 26 fruit domestication traits. Among these loci, three candidate genes were highly associated with fruit weight and the sorbitol and catechin content in fruit. We demonstrated that as the allele frequency of the SNPs associated with high polyphenol composition decreased during peach evolution, alleles associated with high sugar content increased significantly. This indicates that there is genetic potential for the breeding of more nutritious fruit with enhanced bioactive polyphenols without disturbing a harmonious sugar and acid balance by crossing with wild species. This study also describes the development of the genomic resources necessary for evolutionary research in peach and provides the large‐scale characterization of key agronomic traits in this crop species.     

A metabolome‐based core hybridisation strategy for the prediction of rice grain weight across environments

Marker‐based prediction holds great promise for improving current plant and animal breeding efficiencies. However, the predictabilities of complex traits are always severely affected by negative factors, including distant relatedness, environmental discrepancies, unknown population structures, and indeterminate numbers of predictive variables. In this study, we utilised two independent F₁ hybrid populations in the years 2012 and 2015 to predict rice thousand grain weight (TGW) using parental untargeted metabolite profiles with a partial least squares regression method. A stable predictive model for TGW was built based on hybrids from the population in 2012 (r = 0.75) but failed to properly predict TGW for hybrids from the population in 2015 (r = 0.27). After integrating hybrids from both populations into the training set, the TGW of hybrids could be predicted but was largely dependent on population structures. Then, core hybrids from each population were determined by principal component analysis and the TGW of hybrids in both environments were successfully predicted (r > 0.60). Moreover, adjusting the population structures and numbers of predictive analytes increased TGW predictability for hybrids in 2015 (r = 0.72). Our study demonstrates that the TGW of F₁ hybrids across environments can be accurately predicted based on parental untargeted metabolite profiles with a core hybridisation strategy in rice. Metabolic biomarkers identified from early developmental stage tissues, which are grown under experimental conditions, may represent a workable approach towards the robust prediction of major agronomic traits for climate‐adaptive varieties.