Phylogeny Derived from Coding Retroviral Genome Organization

When divergence between viral species is large, the analysis and comparison of nucleotide or protein sequences are dependent on mutation biases and multiple substitutions per site leading, among other things, to the underestimation of branch lengths in phylogenetic trees. To avoid the problem of multiply substituted sites, a method not directly based on the nucleic or protein sequences has been applied to retroviruses. It consisted of asking questions about genome structure or organization, and gene function, the series of answers creating coded sequences analyzed by phylogenic software. This method recovered the principal retroviral groups such as the lentiviruses and spumaviruses and highlighted questions and answers characteristic of each group of retroviruses. In general, there was reasonable concordance between the coded genome methodology and that based on conventional phylogeny of the integrase protein sequence, indicating that integrase was fixing mutations slowly enough to marginalize the problem of multiple substitutions at sites. To a first approximation, this suggests that the acquisition of novel genetic features generally parallels the fixation of amino acid substitutions. Received: 18 May 2001 / Accepted: 7 September 2001     

The effect of single nucleotide polymorphism identification strategies on estimates of linkage disequilibrium

At present there is tremendous interest in characterizing the magnitude and distribution of linkage disequilibrium (LD) throughout the human genome, which will provide the necessary foundation for genome-wide LD analyses and facilitate detailed evolutionary studies. To this end, a human high-density single-nucleotide polymorphism (SNP) marker map has been constructed. Many of the SNPs on this map, however, were identified by sampling a small number of chromosomes from a single population, and inferences drawn from studies using such SNPs may be influenced by ascertainment bias (AB). Through extensive simulations, we have found that AB is a potentially significant problem in estimating and comparing LD within and between populations. Specifically, the magnitude of AB is a function of the SNP discovery strategy, number of chromosomes used for SNP discovery, population genetic characteristics of the particular genomic region considered, amount of gene flow between populations, and demographic history of the populations. We demonstrate that a balanced SNP discovery strategy (where equal numbers of chromosomes are sampled from multiple subpopulations) is the optimal study design for generating broadly applicable SNP resources. Finally, we validate our theoretical predictions by comparing our results to publicly available data from ten genes sequenced in 24 African American and 23 European American individuals.     

Meta-analysis,funnel plots and sensitivity analysis

Publication bias is a major problem, perhaps the major problem, in meta-analysis (or systematic reviews). Small studies are more likely to be published if their results are 'significant' than if their results are negative or inconclusive, and so the studies available for review are biased in favour of those with positive outcomes. Correcting for this bias is not possible without making untestable assumptions. In this paper, a sensitivity analysis is suggested which is based on fitting a model to the funnel plot. Some examples are discussed.     

Meta-analysis in applied ecology

This overview examines research synthesis in applied ecology and conservation. Vote counting and pooling unweighted averages are widespread despite the superiority of syntheses based on weighted combination of effects. Such analyses allow exploration of methodological uncertainty in addition to consistency of effects across species, space and time, but exploring heterogeneity remains controversial. Meta-analyses are required to generalize in ecology, and to inform evidence-based decision-making, but the more sophisticated statistical techniques and registers of research used in other disciplines must be employed in ecology to fully realize their benefits.     

What are we missing with only ground‐level mist nets? Using elevated nets at a migration stopover site

ABSTRACT Mist nets deployed in a standard ground‐level fashion capture birds approximately 0.5–2.6 m above the ground. In habitats where the vegetation extends above this height, standard mist net deployment may inadequately sample the targeted avian community and age‐ and sex‐classes within species. Such sampling biases may raise questions regarding studies based on data from mist‐net captures. To determine if birds were equally likely to be captured by mist nets at different heights, we constructed a series of paired ground‐level and elevated mist nets (hereafter “net rigs”) at a research station in western New York State. Net rigs were operated during 14 migration seasons from 2000 to 2006 (spring and fall each year), and 19,735 birds of 118 species were captured. Capture rates were significantly higher in ground‐level nets, but 12 species were only captured in elevated nets. Of 44 species with at least 50 captures, 25 species were more likely to be captured in the ground‐level nets and two species in the elevated nets. For four of 18 species, more birds were captured in the elevated nets during fall migration than during spring migration. We conclude that standard ground‐level net placement was more efficient in capturing birds in the secondary growth habitats that we sampled. However, ground‐level nets may not adequately sample the entire targeted community or all age‐ or sex‐classes within species.     

SERT and uncertainty: serotonin transporter expression influences information processing biases for ambiguous aversive cues in mice

The long allele variant of the serotonin transporter (SERT, 5‐HTT) gene‐linked polymorphic region (5‐HTTLPR) is associated with higher levels of 5‐HTT expression and reduced risk of developing affective disorders. However, little is known about the mechanisms underlying this protective effect. One hypothesis is that 5‐HTT expression influences aversive information processing, with reduced negative cognitive bias present in those with higher 5‐HTT expression. Here we investigated this hypothesis using genetically‐modified mice and a novel aversive learning paradigm. Mice with high levels of 5‐HTT expression (5‐HTT over‐expressing, 5‐HTTOE mice) and wild‐type mice were trained to discriminate between three distinct auditory cues: one cue predicted footshock on all trials (CS+); a second cue predicted the absence of footshock (CS?); and a third cue predicted footshock on 20% of trials (CS20%), and was therefore ambiguous. Wild‐type mice exhibited equivalently high levels of fear to the CS+ and CS20% and minimal fear to the CS?. In contrast, 5‐HTTOE mice exhibited high levels of fear to the CS+ but minimal fear to the CS? and the CS20%. This selective reduction in fear to ambiguous aversive cues suggests that increased 5‐HTT expression reduces negative cognitive bias for stimuli with uncertain outcomes.     

Kinship and similarity in residency status structure female social networks in black‐and‐white colobus monkeys (colobus vellerosus)

Kinship shapes female social networks in many primate populations in which females remain in their natal group to breed. In contrast, it is unclear to which extent kinship affects the social networks in populations with female dispersal. Female Colobus vellerosus show routine facultative dispersal (i.e., some females remain philopatric and others disperse). This dispersal pattern allowed us to evaluate if facultative dispersed females form social networks shaped by an attraction to kin, to social partners with a high resource holding potential, or to similar social partners in terms of maturational stage, dominance rank, and residency status. During 2008 and 2009, we collected behavioral data via focal and ad libitum sampling of 61 females residing in eight groups at Boabeng‐Fiema, Ghana. We determined kinship based on partial pedigrees and genotypes at 17 short tandem repeat loci. Kinship influenced coalition and affiliation networks in three groups consisting of long‐term resident females with access to a relatively high number of female kin. In contrast, similar residency status was more important than kinship in structuring the affiliation network in one of two groups that contained recent female immigrants. In populations with female dispersal, the occurrence of kin structured social networks may not only depend on the kin composition of groups but also on how long the female kin have resided together. We found no consistent support for females biasing affiliation toward partners with high resource holding potential, possibly due to low levels of contest competition and small inter‐individual differences in resource holding potential. Am J Phys Anthropol 153:365–376, 2014. © 2013 Wiley Periodicals, Inc.     

The Effect of Mutation and Selection on Codon Adaptation in Escherichia coli Bacteriophage

Studying phage codon adaptation is important not only for understanding the process of translation elongation, but also for reengineering phages for medical and industrial purposes. To evaluate the effect of mutation and selection on phage codon usage, we developed an index to measure selection imposed by host translation machinery, based on the difference in codon usage between all host genes and highly expressed host genes. We developed linear and nonlinear models to estimate the C→T mutation bias in different phage lineages and to evaluate the relative effect of mutation and host selection on phage codon usage. C→T-biased mutations occur more frequently in single-stranded DNA (ssDNA) phages than in double-stranded DNA (dsDNA) phages and affect not only synonymous codon usage, but also nonsynonymous substitutions at second codon positions, especially in ssDNA phages. The host translation machinery affects codon adaptation in both dsDNA and ssDNA phages, with a stronger effect on dsDNA phages than on ssDNA phages. Strand asymmetry with the associated local variation in mutation bias can significantly interfere with codon adaptation in both dsDNA and ssDNA phages.     

Optimization protein productivity of human interleukin-2 through codon usage,gene copy number and intracellular tRNA concentration in CHO cells

Transfer RNA (tRNA) abundance is one of the critical factors for the enhancement of protein productivity in prokaryotic and eukaryotic hosts. Gene copy number of tRNA and tRNA codon usage bias are generally used to match tRNA abundance of protein-expressing hosts and to optimize the codons of recombinant proteins. Because sufficient concentration of intracellular tRNA and optimized codons of recombinant proteins enhanced translation efficiency, we hypothesized that sufficient supplement of host’s tRNA improved protein productivity in mammalian cells. First, the small tRNA sequencing results of CHO-K1 cells showed moderate positive correlation with gene copy number and codon usage bias. Modification of human interleukin-2 (IL-2) through codons with high gene copy number and high codon usage bias (IL-2 HH, modified on Leu, Thr, Glu) significantly increased protein productivity in CHO-K1 cells. In contrast, modification through codons with relatively high gene copy number and low codon usage bias (IL-2 HL, modified on Ala, Thr, Val), or relatively low gene copy number and low codon usage bias (IL-2 LH, modified on Ala, Thr, Val) did not increase IL-2 productivity significantly. Furthermore, supplement of the alanine tRNA or threonine tRNA increased IL-2 productivity of IL-2 HL. In summary, we revealed a potential strategy to enhance productivity of recombinant proteins, which may be applied in production of protein drug or design of DNA vaccine.