Contrast-FEL—A Test for Differences in Selective Pressures at Individual Sites among Clades and Sets of Branches

A number of evolutionary hypotheses can be tested by comparing selective pressures among sets of branches in a phylogenetic tree. When the question of interest is to identify specific sites within genes that may be evolving differently, a common approach is to perform separate analyses on subsets of sequences and compare parameter estimates in a post hoc fashion. This approach is statistically suboptimal and not always applicable. Here, we develop a simple extension of a popular fixed effects likelihood method in the context of codon-based evolutionary phylogenetic maximum likelihood testing, Contrast-FEL. It is suitable for identifying individual alignment sites where any among the K≥2 sets of branches in a phylogenetic tree have detectably different ω ratios, indicative of different selective regimes. Using extensive simulations, we show that Contrast-FEL delivers good power, exceeding 90% for sufficiently large differences, while maintaining tight control over false positive rates, when the model is correctly specified. We conclude by applying Contrast-FEL to data from five previously published studies spanning a diverse range of organisms and focusing on different evolutionary questions.     

Pinocytic uptake and intracellular degradation of N-(2-hydroxypropyl)methacrylamide copolymers a potential drug delivery system

Synthetic ¹²⁵I-labelled N-(2-hydroxypropyl)methacrylamide copolymers containing four different, potentially degradable peptidyl side chains were incubated with rat visceral yolk sacs cultured in vitro. All copolymers were captured by fluid-phase pinocytosis and three of the side chains were susceptible to lysosomal hydrolysis, resulting in release of [¹²⁵I]iodotyrosine back into the culture medium. Uptake and degradation was completely inhibited by 2,4-dinitrophenol. The thiol-proteinase inhibitor leupeptin did not affect the rate of pinocytosis, but caused different degrees of inhibition of hydrolysis depending on side chain composition.     

Characterization of microsatellite loci for the detection of temporal genetic shifts within a single cohort of the brown demoiselle,Neopomacentrus filamentosus

Neopomacentrus filamentosus, a common damselfish on the Indo–Australian archipelago, undergoes significant shifts in size and mitochondrial genetic structure upon larval settlement and metamorphosis to juvenile stages. We characterized five polymorphic microsatellite loci in order to study temporal genetic shifts within a single generation of N. filamentosus sampled first as larval settlers then again as demersal juvenile recruits. All loci were extremely polymorphic and exhibited high levels of heterozygosity. While all loci from the larval samples conformed to Hardy – Weinberg expectations, significant heterozygote deficiencies were seen in two loci in the juvenile samples, likely due to extreme size‐selective mortality imposed post‐settlement.     

Hepatic DNAJB9 Drives Anabolic Biasing to Reduce Steatosis and Obesity

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Immunosuppression by Mutated Calreticulin Released from Malignant Cells

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Flight loss linked to faster molecular evolution in insects

The loss of flight ability has occurred thousands of times independently during insect evolution. Flight loss may be linked to higher molecular evolutionary rates because of reductions in effective population sizes (N_e) and relaxed selective constraints. Reduced dispersal ability increases population subdivision, may decrease geographical range size and increases (sub)population extinction risk, thus leading to an expected reduction in N_e. Additionally, flight loss in birds has been linked to higher molecular rates of energy-related genes, probably owing to relaxed selective constraints on energy metabolism. We tested for an association between insect flight loss and molecular rates through comparative analysis in 49 phylogenetically independent transitions spanning multiple taxa, including moths, flies, beetles, mayflies, stick insects, stoneflies, scorpionflies and caddisflies, using available nuclear and mitochondrial protein-coding DNA sequences. We estimated the rate of molecular evolution of flightless (FL) and related flight-capable lineages by ratios of non-synonymous-to-synonymous substitutions (dN/dS) and overall substitution rates (OSRs). Across multiple instances of flight loss, we show a significant pattern of higher dN/dS ratios and OSRs in FL lineages in mitochondrial but not nuclear genes. These patterns may be explained by relaxed selective constraints in FL ectotherms relating to energy metabolism, possibly in combination with reduced N_e.     

Genome‐wide scans to detect positive selection in Large White and Tongcheng pigs

Due to the direction, intensity, duration and consistency of genetic selection, especially recent artificial selection, the production performance of domestic pigs has been greatly changed. Therefore, we reasoned that there must be footprints or selection signatures that had been left during domestication. In this study, with porcine 60K BeadChip genotyping data from both commercial Large White and local Chinese Tongcheng pigs, we calculated the extended haplotype homozygosity values of the two breeds using the long‐range haplotype method to detect selection signatures. We found 34 candidate regions, including 61 known genes, from Large White pigs and 25 regions comprising 57 known genes from Tongcheng pigs. Many selection signatures were found on SSC1, SSC4, SSC7 and SSC14 regions in both populations. According to quantitative trait loci and network pathway analyses, most of the regions and genes were linked to growth, reproduction and immune responses. In addition, the average genetic differentiation coefficient F_ST was 0.254, which means that there had already been a significant differentiation between the breeds. The findings from this study can contribute to further research on molecular mechanisms of pig evolution and domestication and also provide valuable references for improvement of their breeding and cultivation.     

Some factors affecting the composition of tropical ichneumonid faunas

An increasing accumulation of data shows that tropical ichneumonid faunas are no more species-rich than extra-tropical ones, despite the fact that most of their host groups show increased tropical species-richness. This lack of increase in ichneumonid species-richness can be attributed to the absence of groups whose hosts are not present (e.g. Ctenopelmatinae) and poor tropical representation by many groups of diurnal koinobionts (e.g. Campopleginae). Low host density has been postulated as a barrier to tropical koinobiont species-richness, but it is here suggested that this is not the only limiting factor as groups of nocturnal koinobionts, such as the Ophioninae, show increased tropical species-richness. It is postulated that koinobionts have the capability of being able to locate sparse hosts, but as they host-search in flight, a prolonged daytime host-searching period in the tropics would expose them to a high level of predation pressure. By being active at night koinobionts can avoid diurnally active predators. It is also postulated that sparse hosts may be located more easily at night and more habitats may be climatically suitable for ichneumonid activity when they are not subject to direct sunlight. Idiobionts, such as the Mesostenini and Pimplini, are more species-rich and morphologically diverse in the tropics than they are in extra-tropical regions. It is suggested that this results from the fact that tropical idiobionts can be active during the whole of the diapausing period, when their hosts are available, whereas activity by temperate idiobionts is prevented by inclement weather. Although many idiobionts are probably less exposed to predators than koinobionts, many have evolved obvious protective devices.     

Substrate specifity of the hexose carrier in the plasmalemma of Chenopodium suspension cells probed by transmembrane exchange diffusion

Substrate specifity of the proton-driven hexose cotransport carrier in the plasmalemma of photoautotrophic suspension cells of Chenopodium rubrum L. has been studies through the short-term perturbation of ¹⁴C-labelled efflux of 3-O-methyl-d-glucose. Efflux, occurring exclusively via carrier-mediated exchange diffusion, is trans-stimulated by the substrate and trans-inhibited by the glucose-transport inhibitors phlorizin (K _1/2=7.9 mM) and its aglucon phloretin (K _1/2=84 μM); with both inhibitors, 3-O-methyl-d-glucose efflux may be blocked completely. Trans-stimulation of efflux (up to fourfold) by a variety of the d-enantiomers of neutral hexoses, including glucose (K _1/2=48 μM), 3-O-methyl-d-glucose (K _1/2=139 μM), and fructose (K _1/2=730 μM), but not by, for instance, d-allose, and l-sorbose, shows that carrier-substrate interaction critically involves the axial position at C-1 and C-3, respectively. We suggest that substrate binding by the Chenopodium hexose carrier involves both hydrophobic interaction with the pyran-ring and hydrogen-ion bonding at C-1 and C-3 of the d-glucose conformation.