One of the most pervasive challenges in molecular phylogenetics is the incongruence between phylogenies obtained using different data sets, such as individual genes. To systematically investigate the ...degree of incongruence, and potential methods for resolving it, we screened the genome sequences of eight yeast species and selected 106 widely distributed orthologous genes for phylogenetic analyses, singly and by concatenation. Our results suggest that data sets consisting of single or a small number of concatenated genes have a significant probability of supporting conflicting topologies. By contrast, analyses of the entire data set of concatenated genes yielded a single, fully resolved species tree with maximum support. Comparable results were obtained with a concatenation of a minimum of 20 genes; substantially more genes than commonly used but a small fraction of any genome. These results have important implications for resolving branches of the tree of life.
The evolution of cis regulatory elements (enhancers) of developmentally regulated genes plays a large role in the evolution of animal morphology. However, the mutational path of enhancer ...evolution--the number, origin, effect, and order of mutations that alter enhancer function--has not been elucidated. Here, we localized a suite of substitutions in a modular enhancer of the ebony locus responsible for adaptive melanism in a Ugandan Drosophila population. We show that at least five mutations with varied effects arose recently from a combination of standing variation and new mutations and combined to create an allele of large phenotypic effect. We underscore how enhancers are distinct macromolecular entities, subject to fundamentally different, and generally more relaxed, functional constraints relative to protein sequences.
In recent years, criticism of the percentage range approach for individualised exercise prescription has intensified and we were concerned that sub-optimal exercise dose (especially intensity) may be ...in part responsible for the variability in the effectiveness of cardiac rehabilitation (CR) programmes in the United Kingdom (UK). The aim was to investigate the fidelity of a structured Phase III CR programme, by monitoring and quantifying exercise training intensity.
Observational study.
The programme comprised 16 sessions over 8 weeks, where patients undertook an interval, circuit training approach within national guidelines for exercise prescription (40-70% heart rate reserve HRR). All patients wore an Apple Watch (Series 0 or 2, Watch OS2.0.1, Apple Inc., California, USA). We compared the mean % heart rate reserve (%HRR) achieved during the cardiovascular training component (%HRR-CV) of a circuit-based programme, with the %HRR during the active recovery phases (%HRR-AR) in a randomly selected cohort of patients attending standard CR. We then compared the mean %HRR-CV achieved with the minimal exercise intensity threshold during supervised exercise (40% HRR) recommended by national governing bodies.
Thirty cardiac patients (83% male; mean age SD 67 10 years; BMI 28.3 4.6 kg∙m-2) were recruited. We captured 332 individual training sessions. The mean %HRR-CV and %HRR-AR were 37 (10) %, and 31 (13) %, respectively. There was weak evidence to support the alternative hypothesis of a difference between the %HRR-CV and 40% HRR. There was very strong evidence to accept the alternative hypothesis that the mean %HRR-AR was lower than the mean %HRR-CV, median standardised effect size 1.1 (95%CI: 0.563 to 1.669), with a moderate to large effect.
Mean exercise training intensity was below the lower limit of the minimal training intensity guidelines for a Phase III CR programme. These findings may be in part responsible for previous reports highlighting the significant variability in effectiveness of UK CR services and poor CRF improvements observed from several prior investigations.
Understanding the mechanisms underlying the morphological divergence of species is one of the central goals of evolutionary biology. Here, we analyze the genetic and molecular bases of the divergence ...of body pigmentation patterns between
Drosophila yakuba and its sister species
Drosophila santomea. We found that loss of pigmentation in
D. santomea involved the selective loss of expression of the
tan and
yellow pigmentation genes. We demonstrate that
tan gene expression was eliminated through the mutational inactivation of one specific
tan cis-regulatory element (CRE) whereas the Tan protein sequence remained unchanged. Surprisingly, we identify three independent loss-of-function alleles of the
tan CRE in the young
D. santomea lineage. We submit that there is sufficient empirical evidence to support the general prediction that functional evolutionary changes at pleiotropic loci will most often involve mutations in their discrete, modular
cis-regulatory elements.
Understanding the genetic basis of the physical and behavioural traits that distinguish humans from other primates presents one of the great new challenges in biology. Of the millions of base-pair ...differences between humans and chimpanzees, which particular changes contributed to the evolution of human features after the separation of the Pan and Homo lineages 5-7 million years ago? How can we identify the 'smoking guns' of human genetic evolution from neutral ticks of the molecular evolutionary clock? The magnitude and rate of morphological evolution in hominids suggests that many independent and incremental developmental changes have occurred that, on the basis of recent findings in model animals, are expected to be polygenic and regulatory in nature. Comparative genomics, population genetics, gene-expression analyses and medical genetics have begun to make complementary inroads into the complex genetic architecture of human evolution.
The primary foundation for contemplating the possible forms of life elsewhere in the Universe is the evolutionary trends that have marked life on Earth. For its first three billion years, life on ...Earth was a world of microscopic forms, rarely achieving a size greater than a millimetre or a complexity beyond two or three cell types. But in the past 600 million years, the evolution of much larger and more complex organisms has transformed the biosphere. Despite their disparate forms and physiologies, the evolution and diversification of plants, animals, fungi and other macroforms has followed similar global trends. One of the most important features underlying evolutionary increases in animal and plant size, complexity and diversity has been their modular construction from reiterated parts. Although simple filamentous and spherical forms may evolve wherever cellular life exists, the evolution of motile, modular mega-organisms might not be a universal pattern.
The independent evolution of morphological similarities is widespread. For simple traits, such as overall body colour, repeated transitions by means of mutations in the same gene may be common. ...However, for more complex traits, the possible genetic paths may be more numerous; the molecular mechanisms underlying their independent origins and the extent to which they are constrained to follow certain genetic paths are largely unknown. Here we show that a male wing pigmentation pattern involved in courtship display has been gained and lost multiple times in a Drosophila clade. Each of the cases we have analysed (two gains and two losses) involved regulatory changes at the pleiotropic pigmentation gene yellow. Losses involved the parallel inactivation of the same cis-regulatory element (CRE), with changes at a few nucleotides sufficient to account for the functional divergence of one element between two sibling species. Surprisingly, two independent gains of wing spots resulted from the co-option of distinct ancestral CREs. These results demonstrate how the functional diversification of the modular CREs of pleiotropic genes contributes to evolutionary novelty and the independent evolution of morphological similarities.
The phylogenetic relationships among most metazoan phyla remain uncertain. We obtained large numbers of gene sequences from metazoans, including key understudied taxa. Despite the amount of data and ...breadth of taxa analyzed, relationships among most metazoan phyla remained unresolved. In contrast, the same genes robustly resolved phylogenetic relationships within a major clade of Fungi of approximately the same age as the Metazoa. The differences in resolution within the two kingdoms suggest that the early history of metazoans was a radiation compressed in time, a finding that is in agreement with paleontological inferences. Furthermore, simulation analyses as well as studies of other radiations in deep time indicate that, given adequate sequence data, the lack of resolution in phylogenetic trees is a signature of closely spaced series of cladogenetic events.
Background Recent concerns have cast doubt over the effectiveness of cardiac rehabilitation CR programmes for improving cardiorespiratory fitness CRF in patients with a history of cardiac disease in ...the United Kingdom UK. We aimed to characterise the weekly progression of exercise training dose over an 8-week Phase III CR programme as we felt this may be partly responsible for the lack of improvement in CRF reported in previous studies. Design Observational study. Methods We evaluated a community-based Phase III CR programme in the UK. During each training session, patients wore an Apple Watch and the weekly progression of exercise training dose/load was quantified. The analysis was based on 332 individual training sessions. Exercise intensity % heart rate reserve during the cardiovascular CV exercise training component %HRR-CV, CV training duration; estimated changes in cardiorespiratory fitness change in estimated metabolic equivalents (METs); session rating of perceived exertion sRPE, sRPE training load sRPE-TL, and exercise training impulse TRIMP were evaluated. Results Thirty cardiac patients 83% male; age SD 67.0 10.0 years; body mass index SD 28.3 4.6 kg#226;m.sup.-2 were recruited to an 8-week programme 16 sessions in total. Bayesian repeated-measures ANOVA indicated anecdotal evidence for the alternative hypothesis for changes in %HRR-CV (BF.sub.10 = 0.61), sRPE (BF.sub.10 = 1.1), and change in estimated METs (BF.sub.10 = 1.2) during CR. Conversely, Bayesian repeated-measures ANOVA showed extreme evidence for changes in CV training duration (BF.sub.10 = 2.438e+26), TRIMP (BF.sub.10 = 71436), and sRPE-TL (BF.sub.10 = 779570). Conclusion The key exercise training principle of progressive overload was only partially applied. Increases observed in exercise dose were due to increases in the duration of CV training, rather than combined with increases in exercise intensity %HRR-CV and sRPE. Accordingly, allied health professionals must ensure that exercise intensity is more consistently progressed to optimise the exercise stimulus and improvements in CRF and patient outcomes.
How do bacteria regulate their cellular physiology in response to starvation? Here, we present a detailed characterization of Escherichia coli growth and starvation over a time-course lasting two ...weeks. We have measured multiple cellular components, including RNA and proteins at deep genomic coverage, as well as lipid modifications and flux through central metabolism. Our study focuses on the physiological response of E. coli in stationary phase as a result of being starved for glucose, not on the genetic adaptation of E. coli to utilize alternative nutrients. In our analysis, we have taken advantage of the temporal correlations within and among RNA and protein abundances to identify systematic trends in gene regulation. Specifically, we have developed a general computational strategy for classifying expression-profile time courses into distinct categories in an unbiased manner. We have also developed, from dynamic models of gene expression, a framework to characterize protein degradation patterns based on the observed temporal relationships between mRNA and protein abundances. By comparing and contrasting our transcriptomic and proteomic data, we have identified several broad physiological trends in the E. coli starvation response. Strikingly, mRNAs are widely down-regulated in response to glucose starvation, presumably as a strategy for reducing new protein synthesis. By contrast, protein abundances display more varied responses. The abundances of many proteins involved in energy-intensive processes mirror the corresponding mRNA profiles while proteins involved in nutrient metabolism remain abundant even though their corresponding mRNAs are down-regulated.
PDF
