Genome architecture enables local adaptation of Atlantic cod despite high connectivity

Adaptation to local conditions is a fundamental process in evolution; however, mechanisms maintaining local adaptation despite high gene flow are still poorly understood. Marine ecosystems provide a wide array of diverse habitats that frequently promote ecological adaptation even in species characterized by strong levels of gene flow. As one example, populations of the marine fish Atlantic cod (Gadus morhua) are highly connected due to immense dispersal capabilities but nevertheless show local adaptation in several key traits. By combining population genomic analyses based on 12K single nucleotide polymorphisms with larval dispersal patterns inferred using a biophysical ocean model, we show that Atlantic cod individuals residing in sheltered estuarine habitats of Scandinavian fjords mainly belong to offshore oceanic populations with considerable connectivity between these diverse ecosystems. Nevertheless, we also find evidence for discrete fjord populations that are genetically differentiated from offshore populations, indicative of local adaptation, the degree of which appears to be influenced by connectivity. Analyses of the genomic architecture reveal a significant overrepresentation of a large ~5 Mb chromosomal rearrangement in fjord cod, previously proposed to comprise genes critical for the survival at low salinities. This suggests that despite considerable connectivity with offshore populations, local adaptation to fjord environments may be enabled by suppression of recombination in the rearranged region. Our study provides new insights into the potential of local adaptation in high gene flow species within fine geographical scales and highlights the importance of genome architecture in analyses of ecological adaptation.     

Carnitine-dependent transport of acetyl coenzyme A in Candida albicans is essential for growth on nonfermentable carbon sources and contributes to biofilm formation

In eukaryotes, acetyl coenzyme A (acetyl-CoA) produced during peroxisomal fatty acid beta-oxidation needs to be transported to mitochondria for further metabolism. Two parallel pathways for acetyl-CoA transport have been identified in Saccharomyces cerevisiae; one is dependent on peroxisomal citrate synthase (Cit), while the other requires peroxisomal and mitochondrial carnitine acetyltransferase (Cat) activities. Here we show that the human fungal pathogen Candida albicans lacks peroxisomal Cit, relying exclusively on Cat activity for transport of acetyl units. Deletion of the CAT2 gene encoding the major Cat enzyme in C. albicans resulted in a strain that had lost both peroxisomal and mitochondrion-associated Cat activities, could not grow on fatty acids or C(2) carbon sources (acetate or ethanol), accumulated intracellular acetyl-CoA, and showed greatly reduced fatty acid beta-oxidation activity. The cat2 null mutant was, however, not attenuated in virulence in a mouse model of systemic candidiasis. These observations support our previous results showing that peroxisomal fatty acid beta-oxidation activity is not essential for C. albicans virulence. Biofilm formation by the cat2 mutant on glucose was slightly reduced compared to that by the wild type, although both strains grew at the same rate on this carbon source. Our data show that C. albicans has diverged considerably from S. cerevisiae with respect to the mechanism of intracellular acetyl-CoA transport and imply that carnitine dependence may be an important trait of this human fungal pathogen.     

Genotyping single nucleotide polymorphisms by primer extension and high performance liquid chromatography

We have investigated the possibility of genotyping single nucleotide polymorphisms (SNPs) by primer extension and high performance liquid chromatography (HPLC). Using three polymorphisms of current interest to our group (an A/G polymorphism in the proneurotensin gene and A/G and T/C polymorphisms in the 5HT2a receptor gene), we show that robust signal is obtained using this simple analytic method which has the added advantages that sample loading and analysis are essentially automated, analytic time is brief, and no further purification step after primer extension is required. We also show that all stages of the HPLC-primer extension genotyping can be multiplexed which, together with automation, suggests that this system may be suitable for linkage studies based upon emerging SNP maps. Received: 27 April 1998 / Accepted: 26 November 1998     

Transporters involved in uptake of di- and tricarboxylates in Bacillus subtilis

Di- and tricarboxylates found as intermediates in the tricarboxylic acid cycle can be utilized by many bacteria and serve as carbon and energy source under aerobic and anaerobic conditions. A prerequisite for metabolism is that the carboxylates are transported into the cells across the cytoplasmic membrane. Bacillus subtilis is able to metabolize many di- and tricarboxylates and in this overview the available data on all known and putative di- and tricarboxylate transporters in B. subtilis is summarized. The B. subtilis transporters, that are of the secondary type, are discussed in the context of the protein families to which they belong. Available data on biochemical characterization, regulation of gene expression and the physiological function is summarized. It is concluded that in B. subtilis multiple transporters are present for tricarboxylic acid cycle intermediates. This revised version was published online in June 2006 with corrections to the Cover Date.     

Biogeography of the purple nonsulfur bacterium Rhodopseudomonas palustris

The biogeography of the purple nonsulfur bacterium Rhodopseudomonas palustris on a local scale was investigated. Thirty clones of phototrophic bacteria were isolated from each of five unevenly spaced sampling locations in freshwater marsh sediments along a linear 10-m transect, and a total of 150 clones were characterized by BOX-PCR genomic DNA fingerprinting. Cluster analysis of 150 genomic fingerprints yielded 26 distinct genotypes, and 106 clones constituted four major genotypes that were repeatedly isolated. Representatives of these four major genotypes were tentatively identified as R. palustris based on phylogentic analyses of 16S rRNA gene sequences. The differences in the genomic fingerprint patterns among the four major genotypes were accompanied by differences in phenotypic characteristics. These phenotypic differences included differences in the kinetics of carbon source use, suggesting that there may be functional differences with possible ecological significance among these clonal linages. Morisita-Horn similarity coefficients (C(MH)), which were used to compare the numbers of common genotypes found at pairs of sampling locations, showed that there was substantial similarity between locations that were 1 cm apart (C(MH), >/=0.95) but there was almost no similarity between locations that were >/=9 m apart (C(MH), 相似文献   

Disentangling structural genomic and behavioural barriers in a sea of connectivity

Genetic divergence among populations arises through natural selection or drift and is counteracted by connectivity and gene flow. In sympatric populations, isolating mechanisms are thus needed to limit the homogenizing effects of gene flow to allow for adaptation and speciation. Chromosomal inversions act as an important mechanism maintaining isolating barriers, yet their role in sympatric populations and divergence with gene flow is not entirely understood. Here, we revisit the question of whether inversions play a role in the divergence of connected populations of the marine fish Atlantic cod (Gadus morhua), by exploring a unique data set combining whole‐genome sequencing data and behavioural data obtained with acoustic telemetry. Within a confined fjord environment, we find three genetically differentiated Atlantic cod types belonging to the oceanic North Sea population, the western Baltic population and a local fjord‐type cod. Continuous behavioural tracking over 4 year revealed temporally stable sympatry of these types within the fjord. Despite overall weak genetic differentiation consistent with high levels of gene flow, we detected significant frequency shifts of three previously identified inversions, indicating an adaptive barrier to gene flow. In addition, behavioural data indicated that North Sea cod and individuals homozygous for the LG12 inversion had lower fitness in the fjord environment. However, North Sea and fjord‐type cod also occupy different depths, possibly contributing to prezygotic reproductive isolation and representing a behavioural barrier to gene flow. Our results provide the first insights into a complex interplay of genomic and behavioural isolating barriers in Atlantic cod and establish a new model system towards an understanding of the role of genomic structural variants in adaptation and diversification.     

Non-Linear Characterisation of Cerebral Pressure-Flow Dynamics in Humans

Cerebral metabolism is critically dependent on the regulation of cerebral blood flow (CBF), so it would be expected that vascular mechanisms that play a critical role in CBF regulation would be tightly conserved across individuals. However, the relationships between blood pressure (BP) and cerebral blood velocity fluctuations exhibit inter-individual variations consistent with heterogeneity in the integrity of CBF regulating systems. Here we sought to determine the nature and consistency of dynamic cerebral autoregulation (dCA) during the application of oscillatory lower body negative pressure (OLBNP). In 18 volunteers we recorded BP and middle cerebral artery blood flow velocity (MCAv) and examined the relationships between BP and MCAv fluctuations during 0.03, 0.05 and 0.07Hz OLBNP. dCA was characterised using project pursuit regression (PPR) and locally weighted scatterplot smoother (LOWESS) plots. Additionally, we proposed a piecewise regression method to statistically determine the presence of a dCA curve, which was defined as the presence of a restricted autoregulatory plateau shouldered by pressure-passive regions. Results show that LOWESS has similar explanatory power to that of PPR. However, we observed heterogeneous patterns of dynamic BP-MCAv relations with few individuals demonstrating clear evidence of a dCA central plateau. Thus, although BP explains a significant proportion of variance, dCA does not manifest as any single characteristic BP-MCAv function.     

Histological Analysis of Extracranial Carotid Artery Aneurysms

Introduction

Extracranial carotid artery aneurysms (ECAA) are rare but may be accompanied with significant morbidity. Previous studies mostly focused on diagnostic imaging and treatment. In contrast, the pathophysiological mechanisms and natural course of ECAA are largely unknown. Understanding the pathophysiological background may add to prediction of risk for adverse outcome and need for surgical exclusion. The aim of this study was to investigate the histopathological characteristics of ECAA in patients who underwent complete surgical ECAA resection.

Material and Methods

From March 2004 till June 2013, 13 patients were treated with open ECAA repair. During surgery the aneurysm sac was resected and processed for standardized histological analysis. Sections were stained with routine hematoxylin and eosin and special stains to detect elastin, collagen, different types of inflammatory cells, vascular smooth muscle cells and endothelial cells.

Results

Histopathological characterization revealed two distinct categories: dissection (abrupt interruption of the media; n = 3) and degeneration (general loss of elastin fibers in the media; n = 10). In the degenerative samples the elastin fibers in the media were fragmented and were partly absent. Inflammatory cells were observed in the vessel wall of the aneurysms.

Conclusion

Histological analysis in this small sample size revealed dissection and degeneration as the two distinct underlying mechanisms in ECAA formation.     

StartReact Effects Support Different Pathophysiological Mechanisms Underlying Freezing of Gait and Postural Instability in Parkinson’s Disease

Introduction

The pathophysiology underlying postural instability in Parkinson’s disease is poorly understood. The frequent co-existence with freezing of gait raises the possibility of shared pathophysiology. There is evidence that dysfunction of brainstem structures contribute to freezing of gait. Here, we evaluated whether dysfunction of these structures contributes to postural instability as well. Brainstem function was assessed by studying the StartReact effect (acceleration of latencies by a startling acoustic stimulus (SAS)).

Methods

We included 25 patients, divided in two different ways: 1) those with postural instability (HY = 3, n = 11) versus those without (HY<3, n = 14); and 2) those with freezing (n = 11) versus those without freezing (n = 14). We also tested 15 matched healthy controls. We tested postural responses by translating a balance platform in the forward direction, resulting in backward balance perturbations. In 25% of trials, the start of the balance perturbation was accompanied by a SAS.

Results

The amplitude of automatic postural responses and length of the first balance correcting step were smaller in patients with postural instability compared to patients without postural instability, but did not differ between freezers and non-freezers. In contrast, the StartReact effect was intact in patients with postural instability but was attenuated in freezers.

Discussion

We suggest that the mechanisms underlying freezing of gait and postural instability in Parkinson’s disease are at least partly different. Underscaling of automatic postural responses and balance-correcting steps both contribute to postural instability. The attenuated StartReact effect was seen only in freezers and likely reflects inadequate representation of motor programs at upper brainstem level.     

Phytoplankton responses to repeated pulse perturbations imposed on a trend of increasing eutrophication

While eutrophication remains one of the main pressures acting on freshwater ecosystems, the prevalence of anthropogenic and nature‐induced stochastic pulse perturbations is predicted to increase due to climate change. Despite all our knowledge on the effects of eutrophication and stochastic events operating in isolation, we know little about how eutrophication may affect the response and recovery of aquatic ecosystems to pulse perturbations. There are multiple ways in which eutrophication and pulse perturbations may interact to induce potentially synergic changes in the system, for instance, by increasing the amount of nutrients released after a pulse perturbation. Here, we performed a controlled press and pulse perturbation experiment using mesocosms filled with natural lake water to address how eutrophication modulates the phytoplankton response to sequential mortality pulse perturbations; and what is the combined effect of press and pulse perturbations on the resistance and resilience of the phytoplankton community. Our experiment showed that eutrophication increased the absolute scale of the chlorophyll‐a response to pulse perturbations but did not change the proportion of the response relative to its pre‐event condition (resistance). Moreover, the capacity of the community to recover from pulse perturbations was significantly affected by the cumulative effect of sequential pulse perturbations but not by eutrophication itself. By the end of the experiment, some mesocosms could not recover from pulse perturbations, irrespective of the trophic state induced by the press perturbation. While not resisting or recovering any less from pulse perturbations, phytoplankton communities from eutrophying systems showed chlorophyll‐a levels much higher than non‐eutrophying ones. This implies that the higher absolute response to stochastic pulse perturbations in a eutrophying system may increase the already significant risks for water quality (e.g., algal blooms in drinking water supplies), even if the relative scale of the response to pulse perturbations between eutrophying and non‐eutrophying systems remains the same.