The PLOS Genetics Tenth Anniversary Collection

Claudin 1, E-cadherin and keratin 14 in the tail skin of a mouse (October 2014). Image credit: Tia DiTommaso”

Claudin 1, E-cadherin and keratin 14 in the tail skin of a mouse (October 2014). Image credit: Tia DiTommaso

As part of the PLOS Genetics Tenth Anniversary celebrations, we’re launching a special anniversary collection to highlight the best of PLOS Genetics research articles over the last ten years.

In this collection, you’ll find our PLOS Genetics ‘Top Ten’– the ten most downloaded articles from the past ten years. Get started by reading the Editorial from the Editors-in-Chief, Gregory Barsh and Gregory Copenhaver, which introduces the collection and recounts ten reasons to contribute to a community-run journal. The Editorial also includes a series of commentaries from experts in the respective fields, in which they outline why our Top Ten articles have had such an impact. Including a range of topics such as bacteria, primates, population structure and GWAS- the collection is sure to have something to peak your interest. The collection features the image that PLOS Genetics contributors voted their favourite issue image of all time as part of the anniversary celebrations.

While these ten articles represent the best of PLOS Genetics, the collection is by no means exhaustive; PLOS Genetics is chock-full of excellent articles which you can always access through the PLOS Genetics archive. You can find out more about all the Tenth Anniversary Celebration here.

The collection highlights two things PLOS Genetics values greatly – community involvement and excellent research – and we hope you enjoy it! We’re looking forward to the next decad(e)s of presenting cutting-edge research in PLOS Genetics.

Category: Announcement, Biology, Community, Genetics, PLOS Genetics, Research | 1 Comment

Deep Reads: Andreas Vilhelmsson’s journey into the world of global public health

The fifth entry for our Deep Reads blog series is written by Andreas Vilhelmsson, a post-doctoral researcher at the Department of Global Political Studies at Malmö University, Sweden. His research focuses mostly on patient reporting of adverse drug reactions and pharmaceutical regulation with respect to health policy and public health, but he is also interested in broader global health issues like climate change and welfare systems. Currently, he is also writing for the PLOS Student Blog due to his passion for writing and reaching a broader audience.

Laurie Garrett (2000). Betrayal of Trust: the Collapse of Global Public Health. New York: Hyperion

It’s not every day you read something that completely alters your perspective. A couple of years ago, I stumbled upon the book Betrayal of Trust: the Collapse of Global Public Health by Pulitzer Prize-winning journalist Laurie Garrett. At the time, as a PhD-student, I did not think of public health and genetics in the same sentence, but this changed upon reading this book. What Garrett did was to explore the conditions contributing to the epidemics she described and to stress the importance of genetics in current and future public health.

All of a sudden, public health was also a tale of global security and biological warfare; without the knowledge of modern genetics it would be impossible to comprehend such things as viruses, antibiotic resistance, immunology and inherited disease. You see, Garrett had not just written a book handling the present and future public health; Betrayal of Trust was also a guide to the history, in which Garrett describes, for instance, how Russian scientists had developed a genetically modified strain of anthrax that was resistant to all vaccines and antibiotics, and how nations voluntarily created genetically modified “superbugs”. The scientists she portrayed combined basic biology and public health in an unprecedented manner – it was almost like reading a thriller! Later, this kind of research led to the ethical discussions we have today regarding the controversial research on Avian Influenza A/H5N1, where scientists used mutant strains to construct a deadly virus.


Photomicrograph of Bacillus anthracis. Image credit: CDC. CC0.

Like no other author I had previously encountered, Garrett vividly described the resurgence and spread of drug-resistant strains of disease-causing microbes and the ongoing threat to our health they still represent. As a PhD student in public health, taking my first steps towards an unforeseeable future, this book captured me with the way it described the extraordinary capacity microbes have for generating genetic variation and thus developing antibiotic resistance. Of course I had some understanding of antibiotic resistance, but this was before the public health community and the world at large had begun to understand (at least in a noticeable way) and acknowledge the challenge antimicrobial resistance poses to global public health. Back then, it was more seen as a healthcare-related problem and not a public health problem. Now we know that the methicillin-resistant Staphylococcus aureus (MRSA) bacteria can even affect us outside the walls of the hospital.


Petri dish demonstrating the growth of methicillin-resistant Staphylococcus aureus (MRSA) bacteria. Content provider: CDC/ Melissa Dankel. Photo courtesy: James Gathany. CC0.

The Betrayal of Trust, in a very straightforward manner, gives its reader valuable insights in to how resilient and mutated strains of multidrug-resistant bacteria and tuberculosis-causing mycobacteria have evolved by natural selection and flourished, in part by the overuse and misuse of antimicrobial drugs. Once a triumph for global public health, tuberculosis has yet again become a problem, with drug-resistant strains of the microbe. Over time, Garrett writes, an intricate web of human activities had been directly promoting the evolution of bacteria and their resultant resistance to antibiotic drugs. Antibiotics were, and are, highly overused worldwide, and in nearly half of all common infections, inappropriately prescribed to treat viral rather than bacterial conditions. Widespread use of antibiotics in the livestock industry provides further pressure for the evolution of superbugs.


Digitally-colorized scanning electron micrograph (SEM) of Mycobacterium tuberculosis. Image credit: National Institute of Allergy and Infectious Diseases (NIAID). CC0.

What is most saddening is the decline in public health on the global arena – almost to a state of chaos – that Garrett describes. In detail she explains how poorly prepared the world’s public health systems are to deal with disease outbreaks. Even with the expertise of modern medicine, people in the industrialized world may be surprised to find that they are totally unprepared for the challenges of a forthcoming global public health catastrophe.

As Garrett argues, we need to develop new and continuing global partnerships with an ambitious, comprehensive agenda to readdress public health policies for the intervention and prevention of epidemic infectious disease. Today, many of us trust the effectiveness of medical science and our public health systems for protection, but at the same time we live in a world in which new pathogens emerge and old infectious diseases can reemerge, mutated and even more dangerous than before. Here we have the genetic knowledge to work towards solving many of these threats, and I hope we start focusing on this as a wider community.

The Betrayal of Trust truly inspired me as a public health researcher and encouraged me to broaden my view on public health and understand all public health problems as essentially global public health problems. The book is a must-read for every public health student (and everyone else!).

Category: Blog, Disease, Genetics, Infectious disease, PLOS Genetics | Tagged , , , , , , , | Comments Off on Deep Reads: Andreas Vilhelmsson’s journey into the world of global public health

Understanding Images: Seeing Myopia for What it Is- Potentially Treatable

In a post reflecting on August’s PLOS Genetics issue image, Andrei Tkatchenko explains the science behind the image.

Author: Andrei V. Tkatchenko, Columbia University Medical Center, New York, USA

Competing interests: Andrei V. Tkatchenko is an author of the article discussed in this blog                    

Image Credit: Andrei V. Tkatchenko

Image Credit: Andrei V. Tkatchenko


Myopia (commonly known as nearsightedness) is the most common ocular disorder worldwide.  Genetic factors are believed to play a key role in determining the impact of environmental factors such as reading and ‘nearwork’ on refractive eye development and myopia incidence; however until now, we have lacked experimental proof of this gene-environment interaction. In this issue of PLOS Genetics, using a “systems genetics” approach, which combined gene expression profiling in a monkey model of myopia, GWA studies in a human population and validation of candidate genes in a gene-targeted mouse model of myopia our study identified APLP2 as one of the genes responsible for the gene-environment interaction in myopia.


We are Facing an Epidemic of Myopia

The prevalence of myopia has increased from 25% to 44% of the adult population in the United States of America in the last 30 years, and reached more than 80% in some parts of Asia. Epidemiological data suggest that even low-grade common myopia represents a major risk factor for a number of serious ocular conditions such as cataract, glaucoma, retinal detachment, and myopic maculopathy, and represents the seventh leading cause of blindness. The increasing prevalence of myopia costs the U.S.A. nearly $7.2 billion a year for refractive correction alone, and can have negative effects on self-perception, job and activity choices. It is estimated that 2.5 billion people (1/3 of the world’s population) will be affected by myopia by 2020.


Genes Versus Environment

Image credit: Elaine

Image credit: Elaine, Flickr CC BY

Human population studies suggest that environmental factors, such as nearwork and reading, play an important role in the development of myopia [1-4]. These factors are associated with a so-called “lag of accommodation”, i.e., insufficiently strong accommodative response for near objects, which places the plane of focus behind the retina when nearwork tasks are performed. The optical blur produced by the lag of accommodation is believed to be the signal that drives excessive eye growth and causes myopia [2, 5-9]. Animal studies also demonstrated that excessive eye growth and myopia can be induced by either optical blur (recapitulated in animal models by placing a diffuser in front of the eye) or hyperopic defocus (mimicked by placing a negative lens in front of the eye). Environmental factors play a very important role in the development of myopia and are responsible for the recent sharp increase in the prevalence of myopia worldwide, however the contribution of genetic factors has been estimated to be between 60% and 90%. Genetic factors play a key role in determining the impact of environmental factors, such as reading and nearwork, on refractive eye development and development of myopia. In the context of refractive eye development, understanding how genes and environmental factors interact is key to understanding the mechanisms of myopia.


A Risk Variant of APLP2 Causes Myopia in Children who Engage in Above-Average Levels of Reading

Our study found that APLP2 is associated with myopia in children and adults. Moreover, further analysis revealed that children who carry a specific version (risk variant) of APLP2 are 5 times more likely to develop myopia if they read more than 1 hour a day, thus providing evidence of interaction between APLP2 and visual environment. Functional analysis of APLP2 in the mouse model of myopia, in which APLP2 was genetically removed from the genome, confirmed gene-environment interaction between APLP2 and visual environment and demonstrated that lack of APLP2 expression leads to a dose-dependent reduction in susceptibility to myopia in mice. Lack of APLP2 also affected electrophysiological properties of the retina resulting in reduced contrast sensitivity, which correlated with reduced susceptibility to myopia. We also found that APLP2 is expressed in a specific subset of amacrine cells, which were shown to be involved in contrast processing. APLP2 expression in these cells seems to be responsible for its effect on contrast sensitivity and susceptibility to myopia.

Image Credit: Flickr

Image Credit: Image Catalog, Flickr CC0

Myopia Therapy in Sight?

With the exception of glasses, lenses and laser surgery, there are currently no treatment options for myopia.  Our study provides hope that myopia can be treated. Our mouse data suggest that reducing the level of APLP2 expression in the retina can significantly reduce susceptibility to myopia. This effect seems to be achieved via modulation of the amacrine cell function, which in turn affects contrast sensitivity. Considering that reduction in APLP2 levels did not affect visual acuity, control of APLP2 expression in the retina may provide the framework for the development of pharmacological treatment options for myopia.


Further information:

Image credit: Andrei V. Tkatchenko

Schematic representation of (A) Hyperopia, (B) Emmetropia and (C) Myopia. Image credit: Andrei V. Tkatchenko

  1. Parssinen O, Lyyra AL (1993) Myopia and myopic progression among schoolchildren: a three-year follow-up study. Invest Ophthalmol Vis Sci 34: 2794-2802.
  2. Goss DA (2000) Nearwork and myopia. Lancet 356: 1456-1457.
  3. Hepsen IF, Evereklioglu C, Bayramlar H (2001) The effect of reading and near-work on the development of myopia in emmetropic boys: a prospective, controlled, three-year follow-up study. Vision Res 41: 2511-2520.
  4. Saw SM, Chua WH, Hong CY, Wu HM, Chan WY, et al. (2002) Nearwork in early-onset myopia. Invest Ophthalmol Vis Sci 43: 332-339.
  5. Gwiazda J, Thorn F, Bauer J, Held R (1993) Myopic children show insufficient accommodative response to blur. Invest Ophthalmol Vis Sci 34: 690-694.
  6. Gwiazda J, Bauer J, Thorn F, Held R (1995) A dynamic relationship between myopia and blur-driven accommodation in school-aged children. Vision Res 35: 1299-1304.
  7. Abbott ML, Schmid KL, Strang NC (1998) Differences in the accommodation stimulus response curves of adult myopes and emmetropes. Ophthalmic Physiol Opt 18: 13-20.
  8. Charman WN (1999) Near vision, lags of accommodation and myopia. Ophthalmic Physiol Opt 19: 126-133.
  9. Gwiazda JE, Hyman L, Norton TT, Hussein ME, Marsh-Tootle W, et al. (2004) Accommodation and related risk factors associated with myopia progression and their interaction with treatment in COMET children. Invest Ophthalmol Vis Sci 45: 2143-2151.
  10. Tkatchenko AV, Tkatchenko TV, Guggenheim JA, Verhoeven VJM, Hysi PG, Wojciechowski R, et al. (2015) APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans. PLoS Genet 11(8): e1005432. doi:10.1371/journal.pgen.1005432
Category: Biology, Blog, Genetics, Genomics, Image, Molecular biology, Open access, PLOS Genetics, Research | Tagged , , , , , , | 1 Comment

Cell Volume, Self-Organisation, and Escher: the PLOS Comp Biol August Issue

Here are our highlights from August’s PLOS Computational Biology


The Role of Cell Volume in the Dynamics of Seizure, Spreading Depression, and Anoxic Depolarization

K+ exchange at the blood-brain barrier. Image Credit: Ullah et al.

K+ exchange at the blood-brain barrier. Image Credit: Ullah et al.

Cell volume changes are ubiquitous in normal and pathological activity of the brain, yet we know little of how cell volume influences neuronal activity. Ghanim Ullah and colleagues perform the first detailed study of the effects of cell volume on neuronal dynamics. By combining the dynamic ion concentrations and volume, conservation of charge, and the energy requirements of the cell within a Hodgkin-Huxley type framework, the authors demonstrate the feasibility of a comprehensive framework encompassing a wide range of neuronal behaviours.


Self-Organization of Microcircuits in Networks of Spiking Neurons with Plastic Synapses

The connectivity of mammalian brains exhibits structure at a wide variety of spatial scales, from the broad (which brain areas connect to which) to the extremely fine (where synapses form on the morphology of individual neurons). A central question in systems neuroscience is how this structure emerges. Brent Doiron and colleagues present a theory for how activity-dependent synaptic plasticity leads to the emergence of neuronal microcircuits. The authors use this theory to show how the form of the plasticity rule can govern the promotion or suppression of different connectivity patterns.



Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways

August Issue Image: Systematic Mapping of Protein Mutational Space. Credit: Rockah-Shmuel et al.

August Issue Image: Systematic Mapping of Protein Mutational Space. Credit: Rockah-Shmuel et al.

We are now in the age of big data. More than ever before, biological discoveries require powerful and flexible tools for managing large datasets, including both visual and statistical tools. Bernhard O. Palsson and colleagues present Escher, a web application that can be used to rapidly build pathway maps. On Escher maps, diverse datasets related to genes, reactions, and metabolites can be quickly contextualized within metabolism and, increasingly, beyond metabolism. Escher is available now for free use at


Category: Cell biology, Community, Computational biology, Data, Molecular biology, Neuroscience, PLOS Computational Biology, Uncategorized | Tagged , , , , | 1 Comment

Launching the PLOS Genetics Research Prize 2015

2014-11-05 15_03_13-Greenshot

September 2007 Issue Image. Electronic rolled fingerprint. Image Credit: Sarah E. Medland

What did you do when you turned 10? Throw a party? Have a sleepover? Eat chocolate cake? We would love to do all these things with our readers, authors and editors (especially the chocolate cake), but after much deliberation, we decided on a more research-oriented birthday treat.

We’re awarding a US$5000 prize for the best PLOS Genetics Research Article published in 2014. We’re very excited about this opportunity to recognize the outstanding work we publish and, at the same time, involve the genetics community in the selection process for this!

We’re taking nominations from the public until Wednesday September 16 2015 10:59 AM UTC, and our senior editorial team will select the final winner based on those nominations. To reflect the journal’s aims of publishing high quality research and fostering community engagement, the winning Research Article will be chosen based upon scientific excellence and community impact.

Brithday Cake US

Birthday Cake. Image from Flickr. CC0 US Government work.

Please join us in the celebrations and nominate your favorite paper! For more information on the Prize, please see the Program Page and Program Rules. Questions regarding the Prize can also be sent to

Category: Genetics, Uncategorized | Tagged , | 1 Comment

Understanding Images: Plants Limit Crossovers

Authors: Javier Varas and Mónica Pradillo from Universidad Complutense de Madrid, Madrid, Spain.

Competing interests: Javier Varas and Mónica Pradillo are authors of the work discussed in this blog.

In the July issue of PLOS Genetics, the regulation of meiotic crossover in plants was investigated by Varas et al.

Meiosis is a key event in the life of all sexually reproductive organisms, with major implications on the transmission of genetic information and on genome evolution. This process requires specialized features to generate haploid gametes from diploid cells. Meiosis consists of two divisions without an intervening S phase. During the first meiotic division, the formation of chiasmata between homologous chromosomes holds them together to promote their accurate segregation. These connections prevent uneven distribution of chromosomes that could lead to aneuploidy, as in Down syndrome. Chiasmata are the cytological manifestations of reciprocal interchanges of DNA (crossovers) and homologous recombination is the molecular process underlying the formation of crossovers.

Arabidopsis thaliana. Image credit: Varas et al, 2015.

Arabidopsis thaliana. Image credit: Varas et al, 2015.

Meiotic crossovers result from the repair of double-strand DNA breaks induced by SPO11. These double-strand breaks can be processed by multiple recombination pathways with specific intermediates to generate either non-reciprocal interchanges, non-crossovers, or reciprocal interchanges, crossovers. Crossover distribution is non-random and is tightly regulated by several mechanisms. All chromosomes receive at least one crossover (an obligate crossover), and formation of a crossover at a given site generally reduces crossover formation at adjacent regions – a phenomenon known as positive interference. In addition, crossover homeostasis ensures a stable number of crossovers despite variability in the number of double-strand breaks.

Meiotic Recombination in Plants

In plants, most of our knowledge about meiotic recombination has come through studies of the model species Arabidopsis thaliana. We have selected this species to demonstrate that in plants, as in yeast and mouse, increased double-strand break formation is not accompanied by increased crossover formation. Our study describes the meiotic phenotype of the Atfas1-4 mutant, defective for the large subunit of the histone chaperone CAF-1. This mutant shows developmental abnormalities; their stems, roots, siliques (seed pods) and flowers are reduced in size and the leaves are serrated. It also has reduced heterochromatin content and increased frequency of somatic homologous recombination.

Regulation of Crossover Formation in Arabidopsis                  

Image credit: Varas et al, 2015

Image credit: Varas et al, 2015

Arabidopsis has approximately 15 times more double-strand breaks than crossovers. To estimate the number of double-strand breaks in Atfas1-4, we counted foci corresponding to phosphorylated histone H2AX (γH2AX), a sensitive marker that can be used to examine the DNA damage produced and the subsequent repair of the DNA lesion, and the recombinases AtRAD51 and AtDMC1 which are involved in DNA strand invasion during the beginning of the homologous recombination process. In our issue image, the cell on the right corresponds to a dual immuno-localization of the axial element protein AtASY1 (shown in green in the above image) and AtRAD51 (shown in red). We concluded that the number of double-strand breaks is increased by more than 50% in Atfas1-4.

These extra double-strand breaks could be processed by the different pathways which participate in normal conditions; nevertheless, we did not detect an increase in crossovers. We tested whether non-crossover gene conversion frequencies change in Atfas1-4 relative to wild-type plants. To estimate the gene conversion frequencies we used lines with fluorescent pollen grains. Pollen tetrads from plants heterozygous for fluorescent and non-fluorescent alleles present two fluorescent pollen grains and two non-fluorescent pollen grains (top left tetrad in the figure). If gene conversion occurs, a non-Mendelian 3:1 ratio is observed (bottom left tetrad). In the mutant the frequency of these tetrads was increased compared to the wild-type. Therefore, in Atfas1-4 the excess of double-strand breaks produces an increase in the frequency of gene conversion events.

Implications of Findings

Image credit: Varas et al, 2015.

Image credit: Varas et al, 2015.

Our findings show that the number of crossovers can be constrained in plant species even when the number of double-strand breaks increases during meiosis. The extra double strand breaks produced in Atfas1-4 are processed to non-crossovers in order to keep the same crossover frequency as the wild type, resulting in an increase in gene conversion frequency. These results highlight the complex regulation of crossover formation during Arabidopsis meiosis. Our results demonstrate that despite considerable divergence in molecular components that drive meiosis, there is conservation of the homeostatic mechanism which regulates recombination from fungi to plants to animals.

Original Article

Varas J, Sánchez-Morán E, Copenhaver GP, Santos JL, Pradillo M (2015) Analysis of the Relationships between DNA Double-Strand Breaks, Synaptonemal Complex and Crossovers Using the Atfas1-4  PLoS Genet 11(7): e1005301. doi:10.1371/journal.pgen.1005301

Category: Uncategorized | 1 Comment

The Trouble with Transparency

Last week we posted an article by two journalists, Paul D. Thacker and Charles Seife, who argued that the integrity of the scientific and medical literature depends on protecting tools that ensure greater transparency about financial ties to industry that could potentially bias research results. We have heard from many groups who were deeply offended by the article. Our intention was not to cause offense and we wish to express our apologies to any members of the scientific community who felt the post misrepresented their situation. A desire for transparency is in line with the competing interests policies of PLOS, but we appreciate that the realities of implementation may pose challenges. We have since offered to others, including Dr. Kevin Folta, one of the cases mentioned in the post, the opportunity to contribute their views to the debate, under similar conditions, on this blog.

The tools in question in the original piece by Thacker and Seife include public records and Freedom of Information Act requests. These tools, the authors argue, give reporters, and members of the public, access to documents with the potential to uncover undeclared conflicts of interest, dubious research practices, fraud and scientific misconduct. Without these tools, the authors go on to say, the integrity of the scientific and medical literature could be in jeopardy.

We felt the message—that if researchers disclose any and all ties, financial or otherwise, to industries that benefit from research that they engage in, it helps build public confidence in that research by virtue of showing there is nothing to hide—is one that is well worth debating.

That financial conflicts of interest can influence research results is well-documented in the scientific and medical literature. Against a backdrop where research output doubles nearly every decade and concerns over fraud, misconduct and research reliability are on the rise, we at PLOS Biology believe that efforts to boost scientific integrity, literacy and transparency are sorely needed. That’s why when two journalists with a track record for exposing corruption in science came to us with an article outlining the reasons to protect tools to ensure transparency – even though many scientists see the tools as invasive and disruptive — we offered to consider their piece for our blog.

Nonetheless, we appreciate that some of the parties mentioned in the article took grave offense at the authors’ characterization of their situation. In particular, Dr. Kevin Folta, one of several cases mentioned in the article, has publicly stated some of his issues with the article and the authors’ interpretation. Unfortunately, our processes went wrong and we failed to respond as quickly as we should have to Dr. Folta’s initial message to us. We are reviewing our processes to ensure that a similar failure will not be repeated.

We continue to believe that this is an important, if highly charged, issue that merits discussion. On Monday we offered Dr. Folta the opportunity to provide his views on conflicts of interest on PLOS Biologue. We invite your comments and are currently approaching others to showcase and present a variety of views and experiences relating to the FOIA, COI disclosures and transparency in scientific research and publishing.


Category: Debate, Editorial policy, Funding, Publishing, Research | 5 Comments

Post Removed by PLOS – The Fight Over Transparency: Round Two


Statement from PLOS:

PLOS Blogs is, and will continue to be, a forum that allows scientists to debate controversial topics. However, given additional information for further inquiry and analysis, PLOS has determined that the Biologue post that had occupied this page, “The Fight over Transparency: Round Two,” was not consistent with at least the spirit and intent of our community guidelines. PLOS has therefore decided to remove the post, while leaving the comments on it intact. We believe that this topic is important and that it should continue to be discussed and debated, including on PLOS blogs and in PLOS research articles.

We sincerely apologize for any distress that the content of this post caused any individual. Comments and questions can be sent to

Category: Debate, Funding, Policy, Research | Tagged , , , , , , , , | 33 Comments

Microbiome Evolution, Molecular Recognition and Interaction Webs: the PLOS Comp Biol July Issue

Here are our highlights from July’s PLOS Computational Biology


Neutral Models of Microbiome Evolution

There has been an explosion of research on host-associated microbial communities (i.e.,microbiomes) and how they correlate with host health, disease, phenotype, physiology and ecology. However, few studies have focused on how these microbiomes may have evolved. Qinglong Zeng and colleagues develop an agent-based framework to study the dynamics of microbiome evolution. Their framework incorporates neutral models of how hosts acquire their microbiomes, and how the environmental microbial community that is available to the hosts is assembled.


Markov State Models Reveal a Two-Step Mechanism of miRNA Loading into the Human Argonaute Protein

July Issue Image: Hydrophobic Gating of Ion Permeation in Magnesium Channel CorA. Credit: Pomès et al.

July Issue Image: Hydrophobic Gating of Ion Permeation in Magnesium Channel CorA. Credit: Pomès et al.

Argonaute (Ago) proteins and microRNAs (miRNAs) are central components in RNA interference, which is a key cellular mechanism for sequence-specific gene silencing. Despite intensive studies, molecular mechanisms of how Ago recognizes miRNA remain largely elusive. Xuhui Huang and colleagues propose a two-step mechanism for this molecular recognition: selective binding followed by structural re-arrangement. Their results hold the potential to be widely applied in the studies of other molecular recognition systems.


What Can Interaction Webs Tell Us About Species Roles?

Matrix structure of complete Tatoosh network, organized by groups. Credit: Sander et al.

Matrix structure of complete Tatoosh network, organized by groups. Credit: Sander et al.

Ecological interactions are highly diverse, even when considering a single species: the species might feed on a first, disperse the seeds of a second, and pollinate a third. Elizabeth L. Sander and colleagues extend the group model – a method for identifying broad patterns of interaction across a food web – to networks which contain multiple types of interactions. Using this new method, the authors test whether combining different interaction types leads to a better definition of the roles species play in ecological communities.

Category: Biology, Cell biology, Ecology, Microbiology, PLOS Computational Biology, Uncategorized | Tagged , , , , | 1 Comment

Understanding Images: A Genetic Framework in Legumes Controls Infection of Nodules


In a piece reflecting on June’s PLOS Genetics issue image, authors Simon Kelly and Simona Radutoiu discuss the science behind their image.

Authors: Simon Kelly and Simona Radutoiu, Aarhus University, and Carbohydrate Recognition and Signalling Centre in Denmark.

Competing interests: Simon Kelly and Simona Radutoiu are authors of the paper discussed in this blog.

Confocal laser scanning microscopy image of a nodule section illustrating the internal infection pattern of the endophyte Rhizobium mesosinicum, strain KAW12 (red) and of the incompatible symbiont Mesorhizobium loti, strain exoU (green). Image Credit: Rafal Zgadzaj

Confocal laser scanning microscopy image of a nodule section illustrating the internal infection pattern of the endophyte Rhizobium mesosinicum, strain KAW12 (red) and of the incompatible symbiont Mesorhizobium loti, strain exoU (green). Image Credit: Rafal Zgadzaj

The soil environment harbors a diverse range of bacteria, many of which could potentially be detrimental if they are able to gain entry to plant tissues. We are interested in determining how the host plant selects which bacteria are able to colonize its tissues and to identify important endophyte factors that allow them to be accommodated by the host plant. In this issue of PLOS Genetics we investigate the genetic components and molecular signals that allow the endophyte Rhizobium mesosinicum strain KAW12 (KAW12) to colonize symbiotically induced nodules on the model legume Lotus japonicus. We have used different symbiotic and endophytic strains and performed mixed inoculations of wild-type or symbiotic L. japonicus mutants in order to identify the respective contributions of the different interacting partners – legume host, symbiont and endophyte.

Colonisation of Lotus japonicus Nodules by Endophytic Bacteria

 Section of an M. loti nodZ-induced nodule presenting KAW12 (*) and M. loti nodZ (arrow) infection. Image credit: Zgadzaj et al.

Section of an M. loti nodZ-induced nodule presenting KAW12 (*) and M. loti nodZ (arrow) infection. Image credit: Zgadzaj et al.

The legume root nodule is a unique environmental niche induced by symbiotic bacteria, where multiple symbiotic and endophytic bacterial species can co-exist. Several endophytes were tested for their ability to colonize L. japonicus nodules that were induced by its usual symbiotic rhizobia (Mesorhizobium loti) in co-inoculation experiments. Our study identified KAW12 as an endophyte that uses the symbiotically induced infection threads to co-colonize L. japonicus nodules without inducing nodule necrosis, providing us with a system to study host and endophyte genetic features that are important for such interactions.

Root hair infection threads (arrows) colonised by M. loti exoU (green) and KAW12 (red). Image credit: Zgadzaj et al.

Root hair infection threads (arrows) colonised by M. loti exoU (green) and KAW12 (red). Image credit: Zgadzaj et al.

Initiation of the symbiotic process requires Nod-factor signaling. Nod factors are signal molecules produced by symbiotic rhizobia and recognized by the plant through Nod-factor receptors. This perception triggers the initiation of the infection pathway, through which rhizobia enter the plant, as well as initiation of nodule organogenesis. Using symbiotic strains that produce different types of Nod factors as co-inoculating partners, we determined that intact Nod-factor signaling provided by the symbiont is required for nodule colonization by the endophytic KAW12 bacteria.


Exopolysaccharides are Key for Chronic Infection

Exopolysaccharide (EPS) production is important during symbiosis5. The M. loti exoU strain utilized in this study is affected in EPS biosynthesis and is thus impaired in symbiosis due to an inability to form infection threads. To further investigate this we isolated an EPS-deficient strain of KAW12 and performed co-inoculation experiments with M. loti exoU. Strikingly, nodule colonization by the KAW12 EPS mutant was absent, indicating that EPS is a key molecule required by the endophyte to allow for nodule colonization.

Endophyte Nodule Occupancy is Host-Controlled

To study the role of the legume host in mixed inoculations we took advantage of the large collection of L. japonicus mutants available to identify host genetic components required for nodule colonization by the endophyte. Our results revealed that the mutation of genes required for infection thread formation prevented nodule colonization by the KAW12 endophyte. In contrast, KAW12 colonization of nodules formed on plant mutants in genes required for supporting nitrogen-fixation within nodules was not impaired.

L. japonicus. Image credit: Kazuhiro Tsugita, Flickr.

L. japonicus. Image credit: Kazuhiro Tsugita, Flickr.

The presence of endophytes within legume nodules may restrict the occupancy of effective nitrogen-fixing symbionts and therefore represents a major challenge that contributes to limiting legume cultivation. Our study shows that the well-established genetic resources available for the model legume L. japonicus can be utilised in co-inoculation studies to identify genetic and molecular factors important for determining compatibility with soil bacteria, providing further avenues to address this issue.


References and Further Reading

1          Broghammer, A. et al. Legume receptors perceive the rhizobial lipochitin oligosaccharide signal molecules by direct binding. Proc Natl Acad Sci U S A 109, 13859-13864, doi:10.1073/pnas.1205171109 (2012).

2          Radutoiu, S. et al. Plant recognition of symbiotic bacteria requires two LysM receptor-like kinases. Nature 425, 585-592 (2003).

3         Oldroyd, G. E. D., Murray, J. D., Poole, P. S. & Downie, J. A. The rules of engagement in the legume-rhizobial symbiosis. Annu. Rev. Genet. 45, 119-144, doi:10.1146/annurev-genet-110410-132549 (2011).

4          Kawaharada, Y. et al. Receptor-mediated exopolysaccharide perception controls bacterial infection. Nature 523, 308-12 (2015).

5          Kelly, S. J. et al. Conditional requirement for exopolysaccharide in the Mesorhizobium-Lotus symbiosis. Mol Plant Microbe Interact 26, 319-329, doi:10.1094/mpmi-09-12-0227-r (2013).




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