Evidence for variation in the effective population size of animal mitochondrial DNA

Background: It has recently been shown that levels of diversity in mitochondrial DNA are remarkably constant across animals of diverse census population sizes and ecologies, which has led to the suggestion that the effective population of mitochondrial DNA may be relatively constant. Results: Here we present several lines of evidence that suggest, to the contrary, that the effective population size of mtDNA does vary, and that the variation can be substantial. First, we show that levels of mitochondrial and nuclear diversity are correlated within all groups of animals we surveyed. Second, we show that the effectiveness of selection on non-synonymous mutations, as measured by the ratio of the numbers of non-synonymous and synonymous polymorphisms, is negatively correlated to levels of mitochondrial diversity. Finally, we estimate the effective population size of mitochondrial DNA in selected mammalian groups and show that it varies by at least an order of magnitude. Conclusions: We conclude that there is variation in the effective population size of mitochondria. Furthermore we suggest that the relative constancy of DNA diversity may be due to a negative correlation between the effective population size and the mutation rate per generation

Method to Create Arbitrary Sidewall Geometries in 3-Dimensions Using Liga with a Stochastic Optimization Framework

Disclosed herein is a method of making a three dimensional mold comprising the steps of providing a mold substrate; exposing the substrate with an electromagnetic radiation source for a period of time sufficient to render the portion of the mold substrate susceptible to a developer to produce a modified mold substrate; and developing the modified mold with one or more developing reagents to remove the portion of the mold substrate rendered susceptible to the developer from the mold substrate, to produce the mold having a desired mold shape, wherein the electromagnetic radiation source has a fixed position, and wherein during the exposing step, the mold substrate is manipulated according to a manipulation algorithm in one or more dimensions relative to the electromagnetic radiation source; and wherein the manipulation algorithm is determined using stochastic optimization computations

Transformation and fate of microphytobenthos carbon in subtropical, intertidal sediments: potential for long-term carbon retention revealed by ¹³C-labeling

Microphytobenthos (MPB) are ubiquitous in coastal sediments, but the fate of their production (carbon biomass) is poorly defined. The processing and fate of MPB-derived carbon in subtropical intertidal sediments was investigated through in situ labeling with ¹³C-bicarbonate. Of the added ¹³C, 100% was fixed within ~ 4 h, suggesting that MPB productivity was limited by inorganic carbon availability. Although there was rapid transfer of ¹³C to bacteria (within 12 h), a relatively small fraction of ¹³C was transferred to heterotrophs (up to 12.5% of total fixed ¹³C into bacteria and 0.01% into foraminifera). MPB was the major reservoir for ¹³C throughout the study, suggesting that production of extracellular polymeric substances was limited and/or MPB recycled ¹³C. This retention of ¹³C was reflected in remarkably slow estimated turnover times for the MPB community (66–100 d). Over 31 d, ~ 70% of the ¹³C was lost from sediments. This was primarily via resuspension (~ 55%), enhanced by elevated freshwater flow following rainfall. A further ~ 13% was lost via fluxes of dissolved inorganic carbon during inundation. However, ¹³C losses via dissolved organic carbon fluxes from inundated sediments (0.5%) and carbon dioxide fluxes from exposed sediments (<0.1%) were minimal. The retention of ~ 30% of the carbon fixed by MPB within one tidal exposure after > 30 d, despite high resuspension, demonstrates the potentially substantial longer term retention of MPB-derived carbon in unvegetated sediments and suggests that MPB may contribute to carbon burial ("blue carbon")

Protocol for a process-oriented qualitative evaluation of the Waltham Forest and East London Collaborative (WELC) integrated care pioneer programme using the Researcher-in-Residence model

INTRODUCTION: The integration of health and social care in England is widely accepted as the answer to fragmentation, financial concerns and system inefficiencies, in the context of growing and ageing populations with increasingly complex needs. Despite an expanding body of literature, there is little evidence yet to suggest that integrated care can achieve the benefits that its advocates claim for it. Researchers have often adopted rationalist and technocratic approaches to evaluation, treating integration as an intervention rather than a process. Results have usually been of limited use to practitioners responsible for health and social care integration. There is, therefore, a need to broaden the evidence base, exploring not only what works but also how integrated care can most successfully be implemented and delivered. For this reason, we are carrying out a formative evaluation of the Waltham Forest and East London Collaborative (WELC) integrated care pioneer programme. Our expectation is that this will add value to the literature by focusing on the processes by which the vision and objectives of integrated care are translated through phases of development, implementation and delivery from a central to a local perspective, and from a strategic to an operational perspective. METHODS AND ANALYSIS: The qualitative and process-oriented evaluation uses an innovative participative approach-the Researcher-in-Residence model. The evaluation is underpinned by a critical ontology, an interpretive epistemology and a critical discourse analysis methodology. Data will be generated using interviews, observations and documentary gathering. ETHICS AND DISSEMINATION: Emerging findings will be interpreted and disseminated collaboratively with stakeholders, to enable the research to influence and optimise the effective implementation of integrated care across WELC. Presentations and publications will ensure that learning is shared as widely as possible. The study has received ethical approval from University College London's Research Ethics Committee and has all appropriate NHS governance clearances

The role of mutation rate variation and genetic diversity in the architecture of human disease

Background We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher in genes associated with disease, unless all genes that could cause disease have already been identified. Results Consistent with our predictions we find that genes associated with Mendelian and complex disease are substantially longer than non-disease genes. However, we find that both Mendelian and complex disease genes are found in regions of the genome with relatively low mutation rates, as inferred from intron divergence between humans and chimpanzees, and they are predicted to have similar rates of non-synonymous mutation as other genes. Finally, we find that disease genes are in regions of significantly elevated genetic diversity, even when variation in the rate of mutation is controlled for. The effect is small nevertheless. Conclusions Our results suggest that gene length contributes to whether a gene is associated with disease. However, the mutation rate and the genetic architecture of the locus appear to play only a minor role in determining whether a gene is associated with disease

A non-linear optimal estimation inverse method for radio occultation measurements of temperature, humidity and surface pressure

An optimal estimation inverse method is presented which can be used to retrieve simultaneously vertical profiles of temperature and specific humidity, in addition to surface pressure, from satellite-to-satellite radio occultation observations of the Earth's atmosphere. The method is a non-linear, maximum {\it a posteriori} technique which can accommodate most aspects of the real radio occultation problem and is found to be stable and to converge rapidly in most cases. The optimal estimation inverse method has two distinct advantages over the analytic inverse method in that it accounts for some of the effects of horizontal gradients and is able to retrieve optimally temperature and humidity simultaneously from the observations. It is also able to account for observation noise and other sources of error. Combined, these advantages ensure a realistic retrieval of atmospheric quantities. A complete error analysis emerges naturally from the optimal estimation theory, allowing a full characterisation of the solution. Using this analysis a quality control scheme is implemented which allows anomalous retrieval conditions to be recognised and removed, thus preventing gross retrieval errors. The inverse method presented in this paper has been implemented for bending angle measurements derived from GPS/MET radio occultation observations of the Earth. Preliminary results from simulated data suggest that these observations have the potential to improve NWP model analyses significantly throughout their vertical range.Comment: 18 (jgr journal) pages, 7 figure

Reduced performance of native infauna following recruitment to a habitat-forming invasive marine alga

Despite well-documented negative impacts of invasive species on native biota, evidence for the facilitation of native organisms, particularly by habitat-forming invasive species, is increasing. However, most of these studies are conducted at the population or community level, and we know little about the individual fitness consequences of recruitment to habitat-forming invasive species and, consequently, whether recruitment to these habitats is adaptive. We determined the consequences of recruitment to the invasive green alga Caulerpa taxifolia on the native soft-sediment bivalve Anadara trapezia and nearby unvegetated sediment. Initially, we documented the growth and survivorship of A. trapezia following a natural recruitment event, to which recruitment to C. taxifolia was very high. After 12 months, few clams remained in either habitat, and those that remained showed little growth. Experimental manipulations of recruits demonstrated that all performance measures (survivorship, growth and condition) were significantly reduced in C. taxifolia sediments compared to unvegetated sediments. Exploration of potential mechanisms responsible for the reduced performance in C. taxifolia sediments showed that water flow and water column dissolved oxygen (DO) were significantly reduced under the canopy of C. taxifolia and that sediment anoxia was significantly higher and sediment sulphides greater in C. taxifolia sediments. However, phytoplankton abundance (an indicator of food supply) was significantly higher in C. taxifolia sediments than in unvegetated ones. Our results demonstrate that recruitment of native species to habitat-forming invasive species can reduce growth, condition and survivorship and that studies conducted at the community level may lead to erroneous conclusions about the impacts of invaders and should include studies on life-history traits, particularly juveniles. © 2008 Springer-Verlag

How and why DNA barcodes underestimate the diversity of microbial eukaryotes

Background: Because many picoplanktonic eukaryotic species cannot currently be maintained in culture, direct sequencing of PCR-amplified 18S ribosomal gene DNA fragments from filtered sea-water has been successfully used to investigate the astounding diversity of these organisms. The recognition of many novel planktonic organisms is thus based solely on their 18S rDNA sequence. However, a species delimited by its 18S rDNA sequence might contain many cryptic species, which are highly differentiated in their protein coding sequences. Principal Findings: Here, we investigate the issue of species identification from one gene to the whole genome sequence. Using 52 whole genome DNA sequences, we estimated the global genetic divergence in protein coding genes between organisms from different lineages and compared this to their ribosomal gene sequence divergences. We show that this relationship between proteome divergence and 18S divergence is lineage dependant. Unicellular lineages have especially low 18S divergences relative to their protein sequence divergences, suggesting that 18S ribosomal genes are too conservative to assess planktonic eukaryotic diversity. We provide an explanation for this lineage dependency, which suggests that most species with large effective population sizes will show far less divergence in 18S than protein coding sequences. Conclusions: There is therefore a trade-off between using genes that are easy to amplify in all species, but which by their nature are highly conserved and underestimate the true number of species, and using genes that give a better description of the number of species, but which are more difficult to amplify. We have shown that this trade-off differs between unicellular and multicellular organisms as a likely consequence of differences in effective population sizes. We anticipate that biodiversity of microbial eukaryotic species is underestimated and that numerous ''cryptic species'' will become discernable with the future acquisition of genomic and metagenomic sequences

Temporal dynamics of aquatic communities and implications for pond conservation

Conservation through the protection of particular habitats is predicated on the assumption that the conservation value of those habitats is stable. We test this assumption for ponds by investigating temporal variation in macroinvertebrate and macrophyte communities over a 10-year period in northwest England. We surveyed 51 ponds in northern England in 1995/6 and again in 2006, identifying all macrophytes (167 species) and all macroinvertebrates (221 species, excluding Diptera) to species. The alpha-diversity, beta-diversity and conservation value of these ponds were compared between surveys. We find that invertebrate species richness increased from an average of 29. 5 species to 39. 8 species between surveys. Invertebrate gamma-diversity also increased between the two surveys from 181 species to 201 species. However, this increase in diversity was accompanied by a decrease in beta-diversity. Plant alpha-, beta and gamma-diversity remained approximately constant between the two periods. However, increased proportions of grass species and a complete loss of charophytes suggests that the communities are undergoing succession. Conservation value was not correlated between sampling periods in either plants or invertebrates. This was confirmed by comparing ponds that had been disturbed with those that had no history of disturbance to demonstrate that levels of correlation between surveys were approximately equal in each group of ponds. This study has three important conservation implications: (i) a pond with high diversity or high conservation value may not remain that way and so it is unwise to base pond conservation measures upon protecting currently-speciose habitats; (ii) maximising pond gamma-diversity requires a combination of late and early succession ponds, especially for invertebrates; and (iii) invertebrate and plant communities in ponds may require different management strategies if succession occurs at varying rates in the two groups

Evidence for Pervasive Adaptive Protein Evolution in Wild Mice

The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years. The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protein evolution in certain taxa. For example, estimates of the proportion of adaptive amino acid substitutions (alpha) are 50% or more in enteric bacteria and Drosophila. In contrast, recent estimates of alpha for hominids have been at most 13%. Here, we estimate alpha for protein sequences of murid rodents based on nucleotide polymorphism data from multiple genes in a population of the house mouse subspecies Mus musculus castaneus, which inhabits the ancestral range of the Mus species complex and nucleotide divergence between M. m. castaneus and M. famulus or the rat. We estimate that 57% of amino acid substitutions in murids have been driven by positive selection. Hominids, therefore, are exceptional in having low apparent levels of adaptive protein evolution. The high frequency of adaptive amino acid substitutions in wild mice is consistent with their large effective population size, leading to effective natural selection at the molecular level. Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans