Identification and Characterization of a Novel Evolutionarily Conserved Lysine-specific Methyltransferase Targeting Eukaryotic Translation Elongation Factor 2 (eEF2)

The components of the cellular protein translation machinery, such as ribosomal proteins and translation factors, are subject to numerous post-translational modifications. In particular, this group of proteins is frequently methylated. However, for the majority of these methylations, the responsible methyltransferases (MTases) remain unknown. The human FAM86A (family with sequence similarity 86) protein belongs to a recently identified family of protein MTases, and we here show that FAM86A catalyzes the trimethylation of eukaryotic elongation factor 2 (eEF2) on Lys-525. Moreover, we demonstrate that the Saccharomyces cerevisiae MTase Yjr129c, which displays sequence homology to FAM86A, is a functional FAM86A orthologue, modifying the corresponding residue (Lys-509) in yeast eEF2, both in vitro and in vivo. Finally, Yjr129c-deficient yeast cells displayed phenotypes related to eEF2 function (i.e. increased frameshifting during protein translation and hypersensitivity toward the eEF2-specific drug sordarin). In summary, the present study establishes the function of the previously uncharacterized MTases FAM86A and Yjr129c, demonstrating that these enzymes introduce a functionally important lysine methylation in eEF2. Based on the previous naming of similar enzymes, we have redubbed FAM86A and Yjr129c as eEF2-KMT and Efm3, respectively.     

Phylogenetic origins of local-scale diversity patterns and the causes of Amazonian megadiversity

What explains the striking variation in local species richness across the globe and the remarkable diversity of rainforest sites in Amazonia? Here, we apply a novel phylogenetic approach to these questions, using treefrogs (Hylidae) as a model system. Hylids show dramatic variation in local richness globally and incredible local diversity in Amazonia. We find that variation in local richness is not explained primarily by climatic factors, rates of diversification (speciation and extinction) nor morphological variation. Instead, local richness patterns are explained predominantly by the timing of colonization of each region, and Amazonian megadiversity is linked to the long-term sympatry of multiple clades in that region. Our results also suggest intriguing interactions between clade diversification, trait evolution and the accumulation of local richness. Specifically, sympatry between clades seems to slow diversification and trait evolution, but prevents neither the accumulation of local richness over time nor the co-occurrence of similar species.     

From Dinosaurs to Modern Bird Diversity: Extending the Time Scale of Adaptive Radiation

What explains why some groups of organisms, like birds, are so species rich? And what explains their extraordinary ecological diversity, ranging from large, flightless birds to small migratory species that fly thousand of kilometers every year? These and similar questions have spurred great interest in adaptive radiation, the diversification of ecological traits in a rapidly speciating group of organisms. Although the initial formulation of modern concepts of adaptive radiation arose from consideration of the fossil record, rigorous attempts to identify adaptive radiation in the fossil record are still uncommon. Moreover, most studies of adaptive radiation concern groups that are less than 50 million years old. Thus, it is unclear how important adaptive radiation is over temporal scales that span much larger portions of the history of life. In this issue, Benson et al. test the idea of a “deep-time” adaptive radiation in dinosaurs, compiling and using one of the most comprehensive phylogenetic and body-size datasets for fossils. Using recent phylogenetic statistical methods, they find that in most clades of dinosaurs there is a strong signal of an “early burst” in body-size evolution, a predicted pattern of adaptive radiation in which rapid trait evolution happens early in a group''s history and then slows down. They also find that body-size evolution did not slow down in the lineage leading to birds, hinting at why birds survived to the present day and diversified. This paper represents one of the most convincing attempts at understanding deep-time adaptive radiations.

“It is strikingly noticeable from the fossil record and from its results in the world around us that some time after a rather distinctive new adaptive type has developed it often becomes highly diversified.” – G. G. Simpson ([1], pp. 222–223)

George Gaylord Simpson was the father of modern concepts of adaptive radiation—the diversification of ecological traits in a rapidly speciating group of organisms (Figure 1; [2]). He considered adaptive radiation to be the source of much of the diversity of living organisms on planet earth, in terms of species number, ecology, and body form [1]–[3]. Yet more than 60 years after Simpson''s seminal work, the exact role of adaptive radiation in generating life''s extraordinary diversity is still an open and fundamental question in evolutionary biology [3],[4].Open in a separate windowFigure 1An example of adaptive radiation and early bursts in rates of speciation and phenotypic evolution.(a) The adaptive radiation of the modern bird clade Vanginae, which shows early rapid speciation, morphological diversity, and diversity in foraging behavior and diet [15],[32]. (b) Hypothetical curve of speciation rates through time that would be expected in adaptive radiation. The exponential decline in speciation rates shows that there was an “early burst” of speciation at the beginning of the clade''s history. (c) Hypothetical curve of rates of phenotypic evolution through time that would be expected in adaptive radiation, also showing an early burst of evolution with high initial rates. Part (a) is reproduced from [32] with permission (under CC-BY) from the Royal Society and the original authors.To address this question, researchers have looked for signatures of past adaptive radiation in the patterns of diversity in nature. In particular, it has been suggested that groups that have undergone adaptive radiation should show an “early-burst” signal in both rates of lineage diversification and phenotypic evolution through time—a pattern in which rates of speciation and phenotypic evolution are fast early in the history of groups and then decelerate over time (Figure 1; [3]–[5]). These predictions arise from the idea that clades should multiply and diversify rapidly in species number, ecology, and phenotype in an adaptive radiation and that rates of this diversification should decrease later as niches are successively occupied [2].Early bursts have been sought in both fossils and phylogenies. Few fossil studies have discussed their results in the context of adaptive radiation (but see [6]), but they often have found rapid rises in both taxonomic and morphological diversity early in the history of various groups [7], ranging from marine invertebrates [8] to terrestrial mammals [9]. However, fossils often lack the phylogeny needed to model how evolution has proceeded [7]. On the other hand, studies that test for early bursts in currently existing (extant) species typically use phylogenies, which allow us to model past evolution in groups with few or no fossils [5]. Phylogenies have most often been used to test early bursts in speciation (see, e.g., [10]). However, such tests may be misled by past extinction, which will decay the statistical signal of rapid, early diversification [11]. Furthermore, diverse evolutionary scenarios beyond adaptive radiation can give rise to early bursts in speciation [12]. By contrast, studies of phenotypic diversification may be more robust to extinction [13] and they test the distinguishing feature that separates adaptive from nonadaptive radiation [2],[12].Thus, studies of adaptive radiation in extant organisms increasingly have focused on phylogenetic tests of the early-burst model of phenotypic evolution. Some studies show strong support for this prediction in both birds [14],[15] and lizards [5],[16]. However, the most extensive study to date showed almost no support for the early-burst model. In this study, Harmon et al. [17] examined body size in 49 (and shape in 39) diverse groups of animals, including invertebrates, fishes, amphibians, reptiles, birds, and mammals. They found strong support for the early-burst model in only two of these 88 total datasets.This result raises an important question: if adaptive radiation explains most of life''s diversity [1], how is it possible that there is so little phylogenetic evidence for early bursts of phenotypic evolution? One possibility is that early bursts are hard to detect. This can be due to low statistical power in the most commonly employed tests [18]. It may also be due to a lack of precision in the way “early burst” is defined (and thus tested), as the ecological theory of adaptive radiation suggests that the rate of phenotypic evolution will decrease as species diversity increases in a group, not just over time [14],[16]. Indeed, recent studies [14],[16] detected a decline in rates with species diversity in clades that were also in the Harmon et al. [17] study, yet for which no decline over time was detected.A second possible reason for why early-burst patterns are uncommon is more fundamental: the patterns of phenotypic diversity that result from adaptive radiation may be different at large time scales. Many of the best examples of adaptive radiation are in groups that are relatively young, including Darwin''s finches (2.3 million years old [myr]; [19]) and Lake Malawi and Victoria cichlids (2.3 myr; [20]), whereas most groups that are examined for early bursts in phenotypic evolution are much older (e.g., 47 of 49 in Harmon et al. [17]; mean ± sd = 23.8±29.2 myr). So there may be an inherent difference between what unfolds over the relatively short time scales emphasized by Schluter [2] and what one sees at macroevolutionary time scales (see [21] for an in-depth discussion of this idea as it relates to speciation).The time scale over which adaptive radiations unfold has been little explored. As a result, the link between extant diversity and major extinct radiations remains unclear. Simpson [1] believed that adaptive radiation played out at the population level, but that it should manifest itself at larger scales as well—up to phyla (e.g., chordates, arthropods). He suggested that we should see signals of adaptive radiations in large, old clades because they are effectively small-scale adaptive radiation writ large [1]. Under this view, we should see the signal of adaptive radiation even in groups that diversified over vast time scales, particularly if adaptive radiation is as important for explaining life''s diversity as Simpson [1] thought it was.Part of the reason why potential adaptive radiations at deep time scales remain poorly understood is that studies either focus on fossils or phylogenies, but rarely both. In this issue, Benson et al. [22] combine these two types of data to address whether dinosaurs show signs that they adaptively radiated. Unlike most other studies, the temporal scale of the current study is very large—in this case, over 170 million years throughout the Mesozoic era, starting at 240 million years ago in the Triassic period. This characteristic allowed Benson et al. to shed light on deep-time adaptive radiation.The authors estimated body mass from fossils by using measurements of the circumference of the stylopodium shaft (the largest bone of the arm or leg, such as the femur), which shows a consistent scaling relationship with body mass in extant reptiles and mammals [23]. They then combined published phylogenies to obtain a composite phylogeny for the species in their body-size dataset. The authors finally conducted two types of tests of the rate of body-size evolution—tests of early bursts in phenotypic evolution that are the same as those of Harmon et al. [17], as well as an additional less commonly used test that estimates whether differences between estimated body size at adjacent phylogenetic nodes decreases over time.Benson et al. [22] found two striking results. First, in both of their analyses, the early-burst model was strongly supported for most clades of dinosaurs. This early burst began in the Triassic period, indicating that diversification in body size in dinosaurs began before the Triassic-Jurassic mass extinction event would have opened competition-free ecological space (as commonly hypothesized; [24],[25]). Rather, the authors [22] suggest that a key innovation led to this rise in dinosaurs, though it is not clear what this innovation was [26]. In general, though, the finding of an early burst in body-size evolution in most dinosaurs—if a consequence of adaptive evolution—suggests that adaptive radiation may play out over large evolutionary time scales, not just on the short time scales typical of the most well-studied cases of extant groups.Second, one clade—Maniraptora, which is the clade in which modern-day birds are nested—was the only part of the dinosaur phylogeny that did not show such a strong early burst in body-size evolution. Instead, this clade fit a model to a single adaptive peak—an optimum body size, if you will—but also maintained high rates of undirected body-size evolution throughout their history. Benson et al. [22] suggest that this last result connects deep-time adaptive radiation in the dinosaurs, which quickly exhausted the possibility of phenotypic space, with the current radiation in extant birds, which survived to the present day because their constant, high rate of evolution meant that they were constantly undergoing ecological innovation. This gives a glimpse into why modern birds have so many species (an order of magnitude higher than the nonavian dinosaurs) and so much ecological diversity.The use of fossils allowed Benson et al. [22] to address deep-time radiation in dinosaurs and its consequence on present-day bird diversity. Nevertheless, the promise of using fossils to understand adaptive radiation has its limits. The paleontological dataset presented here is exceptional, yet still insufficient to explore major components of adaptive radiations like actual ecological diversification. As in many paleontological studies, Benson et al. used body-size data to represent ecology because body size is one of the few variables that is available for most species. But it is unclear how important body size really is for ecological diversification and niche filling, because body size is important for nearly every aspect of organismal function. Consequently, evolutionary change in body size can result not only from the competition that drives adaptive radiation, but also from predation pressure, reproductive character displacement, and physiological advantages of particular body sizes in a given environment, among other reasons [27].Despite the broad coverage of extinct species presented in Benson et al. [22], the data were insufficient to study another major part of adaptive radiation: early bursts of lineage diversification. While new approaches are becoming available to study diversification with phylogenies containing extinct species [28],[29] or with incomplete fossil data [30], these approaches are limited when many taxa are known from only single occurrences. This is the case in the Benson et al. dataset, and more generally in most fossil datasets.Given that few fossils exist for many extant groups, a major goal for future studies will be the incorporation of incomplete fossil information into analyses primarily focused on traits and clades for which mostly neontological data are available. For example, Slater et al. [31] developed an approach to include fossil information in analyses of phenotypic evolution. They showed that adding just a few fossils (12 fossils in a study of a 135-species clade) drastically increased the power and accuracy of their analyses of extant taxa. Thus, the combination of fossil data and those based on currently living species is important for future studies, as are new approaches that allow analyzing early bursts of lineage diversification along with phenotypic evolution in fossils.So what answers do Benson et al. [22] bring to Simpson''s original question of the importance of adaptive radiation for explaining diversity on earth? The authors present an intriguing and unconventional link between adaptive radiation and the diversity of modern-day birds. They argue that bird diversification was possible because the dinosaur lineage leading to birds did not exhaust niche space, potentially thanks to small body sizes; in contrast, other dinosaur groups adaptively radiated, filled niche space, and thus could not produce the ecological innovation that may have been necessary to survive the Cretaceous-Paleogene mass extinction. This intriguing hypothesis suggests an important role for the relative starting points of successive adaptive radiations in explaining current diversity, giving a new spin to the pivotal question raised by Simpson more than 60 years ago.     

A linkage map of Atlantic salmon (Salmo salar) reveals an uncommonly large difference in recombination rate between the sexes

A genetic linkage map of the Atlantic salmon (Salmo salar) was constructed, using 54 microsatellites and 473 amplified fragment length polymorphism (AFLP) markers. The mapping population consisted of two full-sib families within one paternal half-sib family from the Norwegian breeding population. A mapping strategy was developed that facilitated the construction of separate male and female maps, while retaining all the information contributed by the dominant AFLP markers. By using this strategy, we were able to map a significant number of the AFLP markers for which all informative offspring had two heterozygous parents; these markers then served as bridges between the male and female maps. The female map spanned 901 cM and had 33 linkage groups, while the male spanned 103 cM and had 31 linkage groups. Twenty-five linkage groups were common between the two maps. The construction of the genetic map revealed a large difference in recombination rate between females and males. The ratio of female recombination rate vs. male recombination rate was 8.26, the highest ratio reported for any vertebrate. This map constitutes the first linkage map of Atlantic salmon, one of the most important aquaculture species worldwide.     

Reproductive timing in Eurasian otters on the coast of Norway

The seasonal distribution of reproductive phases in female otters and the recruitment of cubs were studied by using information from carcasses collected along the central and northern coast of Norway Relationships between available prey and female body condition were investigated Conception, partuntion and rearing of cubs, at least up to the age of 5–6 months, occurred successfully at all times of the year However, the main birth peak occurred in summer and autumn The frequency of all phases of the breeding cycle, from follicle enlargement to early stages of cub rearing, vaned consistently between seasons Food availability when the cubs were c 2 months old, and energetic demands on the female assumed to be greatest, was probably the main ultimate cause of the seasonal vananon in the recruitment of cubs Intrautenne mortality, possibly due to the seasonal vanation in body condition of females, and loss of litters, may have been important mechanisms in creaung the seasonal recruitment patterns Although the prey biomass on average showed seasonal vanation, the peak season shifted among years and locations It is argued that the availability of suitable prey for otters tend to be unrelated to the seasonal productivity in aquatic environments, due to species–specific growth and behavior of prey and restnctions on the hunting capability of otters Continuous reproduction with seasonal vanation in birth rates may have been maintained by selection for reproductive riskreduction in a nutritionally unpredictable, although generally seasonal, environment     

Trajectories of sleepiness and insomnia symptoms in Norwegian nurses with and without night work and rotational work

Numerous cross-sectional studies report high prevalence rates of sleepiness and insomnia in shift workers, but few longitudinal studies exist. We investigated trajectories of sleepiness and insomnia symptoms in a sample of Norwegian nurses across four measurements, spanning a total of four years (sleepiness) and five years (insomnia). The participants completed the Epworth Sleepiness Scale and the Bergen Insomnia Scale at each measurement instance. Latent growth curve models were used to analyse the data. Separate models examined night work (night work, entering and leaving night work) and rotational work (rotational work, entering and leaving rotational work) as predictors for trajectories of sleepiness and insomnia symptoms, respectively. Baseline values of sleepiness and insomnia were higher among rotational shift workers than among workers with fixed shifts (day or night). The results showed that night work throughout the period and entering night work during the period were not associated with different trajectories of sleepiness or insomnia symptoms, compared to not having night work. The same results were found for rotational work and entering rotational work, compared to not having rotational work. Leaving night work and leaving rotational work were associated with a decrease in sleepiness and insomnia symptoms, compared to staying in such work.     

Analysis of covariance patterns in gene expression data and FT-IR spectra

The aim of this study was to detect and interpret correlation patterns in several large data matrices from the same biological system using Partial Least Squares Regression (PLSR) in order to get information on the system under investigation. To do this, DNA microarray data and Fourier Transform Infrared (FT-IR) spectra from a designed study where Campylobacter jejuni was exposed to environmental stress conditions, were used. The experimental design included variation in atmospheric conditions, temperature and time. PLSR was first used to analyse each of the two data types separately in order to explore the effect of the experimental parameters on the data. The results showed that both the gene expression and FT-IR spectra were affected by the variations in atmosphere, temperature and time, but that the effect was different for the two types of data. When the DNA microarray data and FT-IR spectra were linked together by PLSR, covariation due to temperature was seen. Both specific genes and ranges in the FT-IR spectra that were connected to the variation in temperature were detected. Some of these are possibly connected to properties of the cell wall of the bacteria. The results in this study show the potential of PLSR for investigation of covariance structures in biological data. By doing this, valuable information about the biological system can be detected and interpreted. It was also shown that the use of FT-IR spectroscopy provided important information about the stress responses in the bacteria, information that was not detected from the DNA microarray data.     

Experimental evaluation of the relationship between lethal or non-lethal virulence and transmission success in malaria parasite infections

Background  

Evolutionary theory suggests that the selection pressure on parasites to maximize their transmission determines their optimal host exploitation strategies and thus their virulence. Establishing the adaptive basis to parasite life history traits has important consequences for predicting parasite responses to public health interventions. In this study we examine the extent to which malaria parasites conform to the predicted adaptive trade-off between transmission and virulence, as defined by mortality. The majority of natural infections, however, result in sub-lethal virulent effects (e.g. anaemia) and are often composed of many strains. Both sub-lethal effects and pathogen population structure have been theoretically shown to have important consequences for virulence evolution. Thus, we additionally examine the relationship between anaemia and transmission in single and mixed clone infections.     

Dynamic patterns of circulating seasonal and pandemic A(H1N1)pdm09 influenza viruses from 2007-2010 in and around Delhi, India

Influenza surveillance was carried out in a subset of patients with influenza-like illness (ILI) presenting at an Employee Health Clinic (EHS) at All India Institute of Medical Sciences (AIIMS), New Delhi (urban) and pediatric out patients department of civil hospital at Ballabhgarh (peri-urban), under the Comprehensive Rural Health Services Project (CRHSP) of AIIMS, in Delhi region from January 2007 to December 2010. Of the 3264 samples tested, 541 (17%) were positive for influenza viruses, of which 221 (41%) were pandemic Influenza A(H1N1)pdm09, 168 (31%) were seasonal influenza A, and 152 (28%) were influenza B. While the Influenza viruses were detected year-round, their types/subtypes varied remarkably. While there was an equal distribution of seasonal A(H1N1) and influenza B in 2007, predominance of influenza B was observed in 2008. At the beginning of 2009, circulation of influenza A(H3N2) viruses was observed, followed later by emergence of Influenza A(H1N1)pdm09 with co-circulation of influenza B viruses. Influenza B was dominant subtype in early 2010, with second wave of Influenza A(H1N1)pdm09 in August-September, 2010. With the exception of pandemic H1N1 emergence in 2009, the peaks of influenza activity coincided primarily with monsoon season, followed by minor peak in winter at both urban and rural sites. Age group analysis of influenza positivity revealed that the percent positivity of Influenza A(H1N1)pdm09 influenza virus was highest in >5–18 years age groups (OR 2.5; CI = 1.2–5.0; p = 0.009) when compared to seasonal influenza. Phylogenetic analysis of Influenza A(H1N1)pdm09 from urban and rural sites did not reveal any major divergence from other Indian strains or viruses circulating worldwide. Continued surveillance globally will help define regional differences in influenza seasonality, as well as, to determine optimal periods to implement influenza vaccination programs among priority populations.