Author: biota

Slotte T, Hazzouri KM, Stern D, Andolfatto P, Wright SI

Evolution 2012 May;66(5):1360-74

PubMed PMID: 22519777

Abstract

The transition from outcrossing to predominant self-fertilization is one of the most common evolutionary transitions in flowering plants. This shift is often accompanied by a suite of changes in floral and reproductive characters termed the selfing syndrome. Here, we characterize the genetic architecture and evolutionary forces underlying evolution of the selfing syndrome in Capsella rubella following its recent divergence from the outcrossing ancestor C. grandiflora. We conduct genotyping by multiplexed shotgun sequencing and map floral and reproductive traits in a large (N= 550) F2 population. Our results suggest that in contrast to previous studies of the selfing syndrome, changes at a few loci, some with major effects, have shaped the evolution of the selfing syndrome in Capsella. The directionality of QTL effects, as well as population genetic patterns of polymorphism and divergence at 318 loci, is consistent with a history of directional selection on the selfing syndrome. Our study is an important step toward characterizing the genetic basis and evolutionary forces underlying the evolution of the selfing syndrome in a genetically accessible model system.

Brito-Melo GE, Nicolato R, de Oliveira AC, Menezes GB, Lélis FJ, Avelar RS, Sá J, Bauer ME, Souza BR, Teixeira AL, Reis HJ

J Psychiatr Res 2012 Jun;46(6):738-42

PubMed PMID: 22497994

Abstract

Schizophrenia is characterized by a slow deteriorating mental illness. Although the pathophysiology mechanisms are not fully understood, different studies have suggested a role for the immune system in the pathogenesis of schizophrenia. To date, an altered expression or signaling of neurotransmitters receptors is observed in immune cells during psychiatric disorders. In the present study, we investigated the expression of different serotonin and dopamine receptors in T-cells of schizophrenic and control patients. We used flow cytometry to determine the pattern of expression of dopamine (D2 and D4) and serotonine receptors (SR1A, SR1C, SR2A, SR2B), as well as serotonin transporter (ST), in T-cell subsets (CD4 and CD8). Expression of serotonin receptors and ST in T-cells of schizophrenic patients were not different from controls. However, the percentages of CD4+D4+ and CD8+D4+ were increased in schizophrenic patients as compared to controls. In addition, increased percentages of CD8+D2+ cells were also observed in schizophrenic patients, albeit this population revealed lower CD4+D2+ cells in comparison to controls. Interestingly, a relationship between clinical symptoms and immunological parameters was also observed. We showed that the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS) and the Abnormal Involuntary Movement Scale (AIMS) were positively related to CD8+D2+ cells, though AIMS was inversely related to CD4+D4+ cells. In conclusion, the alteration in the pattern of cell population and molecules expressed by them might serve as a promising biomarker for diagnosis of schizophrenia.

Maughan H, Cunningham KS, Wang PW, Zhang Y, Cypel M, Chaparro C, Tullis DE, Waddell TK, Keshavjee S, Liu M, Guttman DS, Hwang DM

Pulm Med 2012;2012:746358

PubMed PMID: 22448327

Abstract

Background. Recurrent bacterial infections play a key role in the pathogenesis of bronchiectasis, but conventional microbiologic methods may fail to identify pathogens in many cases. We characterized and compared the pulmonary bacterial communities of cystic fibrosis (CF) and non-CF bronchiectasis patients using a culture-independent molecular approach. Methods. Bacterial 16S rRNA gene libraries were constructed from lung tissue of 10 non-CF bronchiectasis and 21 CF patients, followed by DNA sequencing of isolates from each library. Community characteristics were analyzed and compared between the two groups. Results. A wide range of bacterial diversity was detected in both groups, with between 1 and 21 bacterial taxa found in each patient. Pseudomonas was the most common genus in both groups, comprising 49% of sequences detected and dominating numerically in 13 patients. Although Pseudomonas appeared to be dominant more often in CF patients than in non-CF patients, analysis of entire bacterial communities did not identify significant differences between these two groups. Conclusions. Our data indicate significant diversity in the pulmonary bacterial community of both CF and non-CF bronchiectasis patients and suggest that this community is similar in surgically resected lungs of CF and non-CF bronchiectasis patients.

Nguyen Ba AN, Yeh BJ, van Dyk D, Davidson AR, Andrews BJ, Weiss EL, Moses AM

Sci Signal 2012 Mar;5(215):rs1

PubMed PMID: 22416277

Abstract

At least 30% of human proteins are thought to contain intrinsically disordered regions, which lack stable structural conformation. Despite lacking enzymatic functions and having few protein domains, disordered regions are functionally important for protein regulation and contain short linear motifs (short peptide sequences involved in protein-protein interactions), but in most disordered regions, the functional amino acid residues remain unknown. We searched for evolutionarily conserved sequences within disordered regions according to the hypothesis that conservation would indicate functional residues. Using a phylogenetic hidden Markov model (phylo-HMM), we made accurate, specific predictions of functional elements in disordered regions even when these elements are only two or three amino acids long. Among the conserved sequences that we identified were previously known and newly identified short linear motifs, and we experimentally verified key examples, including a motif that may mediate interaction between protein kinase Cbk1 and its substrates. We also observed that hub proteins, which interact with many partners in a protein interaction network, are highly enriched in these conserved sequences. Our analysis enabled the systematic identification of the functional residues in disordered regions and suggested that at least 5% of amino acids in disordered regions are important for function.

Lumba S, Tsuchiya Y, Delmas F, Hezky J, Provart NJ, Shi Lu Q, McCourt P, Gazzarrini S

BMC Biol. 2012;10:8

PubMed PMID: 22348746

Abstract

BACKGROUND: The embryonic temporal regulator FUSCA3 (FUS3) plays major roles in the establishment of embryonic leaf identity and the regulation of developmental timing. Loss-of-function mutations of this B3 domain transcription factor result in replacement of cotyledons with leaves and precocious germination, whereas constitutive misexpression causes the conversion of leaves into cotyledon-like organs and delays vegetative and reproductive phase transitions.

RESULTS: Herein we show that activation of FUS3 after germination dampens the expression of genes involved in the biosynthesis and response to the plant hormone ethylene, whereas a loss-of-function fus3 mutant shows many phenotypes consistent with increased ethylene signaling. This FUS3-dependent regulation of ethylene signaling also impinges on timing functions outside embryogenesis. Loss of FUS3 function results in accelerated vegetative phase change, and this is again partially dependent on functional ethylene signaling. This alteration in vegetative phase transition is dependent on both embryonic and vegetative FUS3 function, suggesting that this important transcriptional regulator controls both embryonic and vegetative developmental timing.

CONCLUSION: The results of this study indicate that the embryonic regulator FUS3 not only controls the embryonic-to-vegetative phase transition through hormonal (ABA/GA) regulation but also functions postembryonically to delay vegetative phase transitions by negatively modulating ethylene-regulated gene expression.

McCann HC, Nahal H, Thakur S, Guttman DS

Proc. Natl. Acad. Sci. U.S.A. 2012 Mar;109(11):4215-20

PubMed PMID: 22323605

Abstract

The innate immune system is an ancient and broad-spectrum defense system found in all eukaryotes. The detection of microbial elicitors results in the up-regulation of defense-related genes and the elicitation of inflammatory and apoptotic responses. These innate immune responses are the front-line barrier against disease because they collectively suppress the growth of the vast majority of invading microbes. Despite their critical role, we know remarkably little about the diversity of immune elicitors. To address this paucity, we reasoned that hosts are more likely to evolve recognition to “core” pathogen proteins under strong negative selection for the maintenance of essential cellular functions, whereas repeated exposure to host-defense responses will impose strong positive selective pressure for elicitor diversification to avoid host recognition. Therefore, we hypothesized that novel bacterial elicitors can be identified through these opposing forces of natural selection. We tested this hypothesis by examining the genomes of six bacterial phytopathogens and identifying 56 candidate elicitors that have an excess of positively selected residues in a background of strong negative selection. We show that these positively selected residues are atypically clustered, similar to patterns seen in the few well-characterized elicitors. We then validated selected candidate elicitors by showing that they induce Arabidopsis thaliana innate immunity in functional (virulence suppression) and cellular (callose deposition) assays. These finding provide targets for the study of host-pathogen interactions and applied research into alternative antimicrobial treatments.

Cutter AD, Wang GX, Ai H, Peng Y

Mol. Ecol. 2012 Mar;21(6):1345-59

PubMed PMID: 22320847

Abstract

Molecular hyperdiversity has been documented in viruses, prokaryotes and eukaryotes. Such organisms undermine the assumptions of the infinite-sites mutational model, because multiple mutational events at a site comprise a non-negligible portion of polymorphisms. Moreover, different sampling schemes of individuals from species with subdivided populations can profoundly influence resulting patterns and interpretations of molecular variation. Inspired by molecular hyperdiversity in the nematode Caenorhabditis sp. 5, which exhibits average pairwise differences among synonymous sites of >5% as well as modest population structure, we investigated via coalescent simulation the joint effects of a finite-sites mutation (FSM) process and population subdivision on the variant frequency spectrum. From many demes interconnected through a stepping-stone migration model, we constructed local samples from a single deme, pooled samples from several demes and scattered samples of a single individual from numerous demes. Compared with a single panmictic population at equilibrium, we find that high population mutation rates induce a deficit of rare variants (positive Tajima’s D) under a FSM model. Population structure also induces such a skew for local samples when migration is high and for pooled samples when migration is low. Contrasts of sampling schemes for C. sp. 5 imply high mutational input coupled with high migration. We propose that joint analysis of local, pooled and scattered samples for species with subdivided populations provides a means of improving inference of demographic history, by virtue of the partially distinct patterns of polymorphism that manifest when sequences are analyzed according to differing sampling schemes.

Krogan NT, Ckurshumova W, Marcos D, Caragea AE, Berleth T

New Phytol. 2012 Apr;194(2):391-401

PubMed PMID: 22320407

Abstract

Combinatorial interactions of AUXIN RESPONSE FACTORs (ARFs) and auxin/indole acetic acid (Aux/IAA) proteins through their common domains III and IV regulate auxin responses, but insight into the functions of individual proteins is still limited. As a new tool to explore this regulatory network, we generated a gain-of-function ARF genotype by eliminating domains III and IV from the functionally well-characterized ARF MONOPTEROS(MP)/ARF5. This truncated version of MP, termed MP?, conferred complementing MP activity, but also displayed a number of semi-dominant traits affecting auxin signaling and organ patterning. In MP?, the expression levels of many auxin-inducible genes, as well as rooting properties and vascular tissue abundance, were enhanced. Lateral organs were narrow, pointed and filled with parallel veins. This effect was epistatic over the vascular hypotrophy imposed by certain Aux/IAA mutations. Further, in MP? leaves, failure to turn off the procambium-selecting gene PIN1 led to the early establishment of oversized central procambial domains and very limited subsequent lateral growth of the leaf lamina. We conclude that MP? can selectively uncouple a single ARF from regulation by Aux/IAA proteins and can be used as a genetic tool to probe auxin pathways and explore leaf development.

Lee AH, Hurley B, Felsensteiner C, Yea C, Ckurshumova W, Bartetzko V, Wang PW, Quach V, Lewis JD, Liu YC, Börnke F, Angers S, Wilde A, Guttman DS, Desveaux D

PLoS Pathog. 2012 Feb;8(2):e1002523

PubMed PMID: 22319451

Abstract

The eukaryotic cytoskeleton is essential for structural support and intracellular transport, and is therefore a common target of animal pathogens. However, no phytopathogenic effector has yet been demonstrated to specifically target the plant cytoskeleton. Here we show that the Pseudomonas syringae type III secreted effector HopZ1a interacts with tubulin and polymerized microtubules. We demonstrate that HopZ1a is an acetyltransferase activated by the eukaryotic co-factor phytic acid. Activated HopZ1a acetylates itself and tubulin. The conserved autoacetylation site of the YopJ / HopZ superfamily, K289, plays a critical role in both the avirulence and virulence function of HopZ1a. Furthermore, HopZ1a requires its acetyltransferase activity to cause a dramatic decrease in Arabidopsis thaliana microtubule networks, disrupt the plant secretory pathway and suppress cell wall-mediated defense. Together, this study supports the hypothesis that HopZ1a promotes virulence through cytoskeletal and secretory disruption.

Weadick CJ, Chang BS

Mol. Biol. Evol. 2012 May;29(5):1297-300

PubMed PMID: 22319160

Abstract

Maximum likelihood codon substitution models have proven useful for studying when and how protein function evolves, but they have recently been criticized on a number of fronts. The strengths and weaknesses of such methods must therefore be identified and improved upon. Here, using simulations, we show that the Clade model C versus M1a test for functional divergence among clades is prone to false positives under simple evolutionary conditions. We then propose a new null model (M2a_rel) that better accounts for among-site variation in selective constraint. We show that the revised test has an improved false-positive rate and good power. Applying this test to previously analyzed data sets of primate ribonucleases and mammalian rhodopsins reveals that some conclusions may have been misled by the original method. The improved test should prove useful for identifying patterns of divergence in selective constraint among paralogous gene families and among orthologs from ecologically divergent species.