Mimicry Hypothesis Research Articles

Reply: Does Clostridium botulinum neurotoxin A exhibit molecular mimicry with thyroid autoantigens and cause thyroid complications in predisposed persons?

We thank Atassi and Deitiker [1] for the opportunity to give some clarifications. Their references 2 and 3 (the latter published after our paper) report epitopes targeted by protective antibodies against Clostridium botulinum neurotoxin A (Btx), different from our epitopes. However, because our patient was not immunoresistant to 10-year duration of Btx injections, chances are she had non-neutralizing Btx-antibodies. Contiguity of four or more identical aminoacids is not necessary for cross-reaction, and the molecular mimicry hypothesis cannot be rejected on this basis. For example, the peptide YVLEGTLTA (aa 165–173 of Borrelia burgdorferi OspA) experimentally cross-reacts with YVIEGTSKQ (aa 332–340 of human LFA-1) [2]. We agree that only experimental evidence is definitive, but our patient did not return subsequently making impossible further tests with synthetic peptides, other Btx formulations or placebo. We could not find data on the concentration of flagellins in Dysport , nor about possible contamination of other Btx products by flagellins. It is therefore impossible to say whether administration of a different Btx product would make a difference. However, it seems unlikely that flagellins in Dysport can trigger thyroid autoimmunity. Available data [3] suggest that they interact with TLR-5, perhaps acting as adjuvants but not causing anti-flagellin response. Moreover, while many researches detected Btx antibodies, none reported flagellin antibodies following Btx injections. Statistical significance of homologies concerning short peptides not always correlates to biologic significance. For example, an E value of 23 (largely statistically insignificant) is obtained when comparing the aforementioned Borrelia epitope YVLEGTLTA against itself. Although our proposed antigen mimicry needs experimental testing, it cannot be ruled out based on statistics. We never mentioned discontinuous epitopes because we believe that, based on our analysis, they are not involved in this case. Concerning data in our Fig. 1 (left inset), in principle it is correct that the more are the data the more accurate and reliable are correlations. The graphic, based on the only three values available, is meant to show a consistent trend to decrease of TSHR-Ab across months after Btx injection. However, we could not ignore the resulting perfectly linear statistically significant inverse relationship. Finally, the mechanism of antigen presentation, detailed in literature [4], explains HLA-related predisposition to specific autoimmune diseases through molecular mimicry. Peptide binding E. Gregoric Department of Nuclear Medicine, Hospital Izola, Izola, Slovenia

TRNA mimicry in translation termination and beyond

The mechanism of translation termination has long been a puzzle. The release factor (RF) class of translation factors plays a key role in terminating protein synthesis. Bacteria have two RFs, RF1 and RF2, with high specificity to decipher three stop codons. Decades ago, an idea was formulated that RFs may be protein analogs of tRNA. This idea gained substantial support 10 years ago by the identification of two classes of crucial RF peptide motifs, P(A/V)T/SPF and GGQ, in bacteria. These motifs were functionally equivalent to the anticodon and aminoacyl-CCA terminus of tRNA, although the processes these molecules function in are different. These findings reinforced the 'molecular mimicry' or 'tRNA mimicry' hypothesis. Since then, the RF-tRNA mimicry hypothesis has played a crucial role to elucidate the mechanism of translation termination. In the past decade, the crystal structure of the translation termination complex between the ribosome and RFs has been determined at atomic resolution. Overall, the structural data strongly support the RF-tRNA mimicry hypothesis, with shared as well as distinct ribosomal conformations induced by RF or tRNA binding. In this review, we re-evaluate the structural data from the genetic and biochemical viewpoint as our initial functional evidence were not fully interpreted in the previous reports. Recent structural and functional studies of the translation machinery have uncovered that the concept of tRNA mimicry can be expanded for factors beyond translation termination and into translation initiation, elongation, as well as mRNA surveillance pathways for protein synthesis. WIREs RNA 2011 2 647-668 DOI: 10.1002/wrna.81 For further resources related to this article, please visit the WIREs website.

Vaccines against Lyme Disease: What Happened and What Lessons Can We Learn?

This article reviews events that led to the withdrawal of the only vaccine to prevent Lyme disease licensed in the United States. The primary issues that led to the vaccine's withdrawal appear to be a combination of vaccine safety concerns, sparked by a molecular mimicry hypothesis that suggested that the vaccine antigen, outer surface protein A, serves as an autoantigen and hence was arthritogenic; concerns raised by anti-vaccine groups regarding vaccine safety; vaccine cost; a difficult vaccination schedule and the potential need for boosters; class action lawsuits; uncertainty regarding risk of disease; and low public demand. This article reviews lessons learned from these events and proposes that future candidate Lyme disease vaccines are unlikely to be developed, tested, and used within the United States in the near future, thus leaving at-risk populations unprotected.

Are there evidences of a complex mimicry system among Asclepias curassavica (Apocynaceae), Epidendrum fulgens (Orchidaceae), and Lantana camara (Verbenaceae) in Southern Brazil?

The goal of this paper was to test the presence of mimicry in Asclepias curassavica L., Epidendrum fulgens Brong., and Lantana camara L. The study was carried out at the Parque Estadual de Itapeva, RS, southern Brazil, from 2004 to 2006. Flowering period of each of the three species was followed up; focal observations of butterflies visiting flowers, from fixed point and during random walks were carried out. We also estimated the frequency of pollinaria removal in the orchid, as well as its mode of reproduction. All these variables were important for testing the mimicry hypothesis. Despite some temporal coincidences in the flowering period of two plants in the system, there was no statistical association among the three plants as to flowering period. Twenty-nine species of butterflies, as potential pollinators, were recorded, particularly Agraulis vanillae maculosa, Dryas iulia alcionea, Urbanus simplicius, Tegosa claudina, and Heliconius erato phyllis, which were the more frequent visitors of the three plants. There was association between the number of visits to L. camara and E. fulgens, based on Pearson correlation (r = 0.4603; n = 19; P = 0.0473). Pollinaria removal of E. fulgens was low, as measured by the percentage of removal (range: 0 - 10%). The analysis of the mode of reproduction of this orchid showed its pollinator-dependence, since no fruits were formed by spontaneous self-pollination. In contrast, the percentage of fruit set that resulted from geitonogamy and xenogamy was, in average, 86%. The results here shown are not conclusive as to the occurrence of a mimicry system among the three plants.

No human protein is exempt from bacterial motifs, not even one

The hypothesis that mimicry between a self and a microbial peptide antigen is strictly related to autoimmune pathology remains a debated concept in autoimmunity research. Clear evidence for a causal link between molecular mimicry and autoimmunity is still lacking. In recent studies we have demonstrated that viruses and bacteria share amino acid sequences with the human proteome at such a high extent that the molecular mimicry hypothesis becomes questionable as a causal factor in autoimmunity. Expanding upon our analysis, here we detail the bacterial peptide overlapping to the human proteome at the penta-, hexa-, hepta- and octapeptide levels by exact peptide matching analysis and demonstrate that there does not exist a single human protein that does not harbor a bacterial pentapeptide or hexapeptide motif. This finding suggests that molecular mimicry between a self and a microbial peptide antigen cannot be assumed as a basis for autoimmune pathologies. Moreover, the data are discussed in relation to the microbial immune escape phenomenon and the possible vaccine-related autoimmune effects.

Periodontitis in RA—the citrullinated enolase connection

Autoimmunity in rheumatoid arthritis (RA) is characterized by an antibody response to citrullinated proteins. Two of the risk factors for RA-HLA-DRB1 shared epitope alleles and smoking-are also associated with periodontitis, which is largely, but not exclusively, caused by Porphyromonas gingivalis infection. Furthermore, RA and periodontitis have a similar pathophysiology, characterized by destructive inflammation. The citrullination of proteins by P. gingivalis and the subsequent generation of autoantigens that drive autoimmunity in RA represents a possible causative link between these two diseases. Antibodies directed towards the immunodominant epitope of human citrullinated α-enolase cross-react with a conserved sequence on citrullinated P. gingivalis enolase. On the basis of this cross-reactivity, in this Perspectives article we explore the hypothesis of molecular mimicry in the etiology of RA, with citrullinated enolase as the specific antigen involved.

The Subadult Plumage of Male Purple Martins: Variability, Female Mimicry and Recent Evolution

Like a number of other passerine birds year-old male purple martins, Progne subis, often breed in a ♀-like plumage. We have examined delayed plumage maturation in martins by testing assumptions and predictions derived from two hypotheses advanced to explain their appearance and behavior: the sexual selection hypothesis and the female mimicry hypothesis. First, we examine the success of subadults of different appearance 1) in dominance interactions with adults and with other subadults and 2) at entering colonies with different numbers of adults. Second, we compare the mating success of subadults of different appearance. Finally, we examine predictions from the female mimicry hypothesis concerning the appearance of subadults with regard to geographic variation in colony size and with regard to historical changes in colony size in Eastern North America.

The function of animal ‘eyespots’: Conspicuousness but not eye mimicry is key

Abstract Many animals are marked with conspicuous circular features often called ‘eyespots’, which intimidate predators, preventing or halting an attack. It has long been assumed that eyespots work by mimicking the eyes of larger animals, but recent experiments have indicated that conspicuousness and contrast is important in eyespot function, and not eye mimicry. We undertake two further experiments to distinguish between the conspicuousness and mimicry hypotheses, by using artificial prey presented to wild avian predators in the field. In experiment 1, we test if eyespot effectiveness depends on the marking shape (bar or circle) and arrangement (eye-like and non-eye-like positions). We find no difference between shapes or arrangement; all spots were equally effective in scaring birds. In experiment 2, we test if the often yellow and black colors of eyespots mimic the eyes of birds of prey. We find no effect of shape, and no advantage to yellow and black spots over non-eye-like but equally conspicuous colors. The consistent finding is that eyespot function lies in being a conspicuous signal to predators, and not necessarily due to eye mimicry.

Private channel: a single unusual compound assures specific pollinator attraction in Ficus semicordata

Summary 1. Floral scents have been suggested to play a key role in the obligate pollination mutualism between figs and fig wasps. However, few studies have determined whether pollinator‐attractive compounds could alone assure species‐specificity (‘private channel’), or whether specificity is mediated by more complex ‘floral filters’, of which scent is only one component. 2. We examined changes in the floral volatile compounds of Ficus semicordata, a dioecious fig species, during and after pollination using headspace collection and compound identification by Gas Chromatography/Mass Spectrometry (GC/MS). One benzenoid compound, 4‐methylanisole, was strongly predominant (94–98%) among the volatile compounds emitted by both male and female receptive figs of F. semicordata, whereas it was totally absent in the volatiles emitted by figs 4 days after pollination, as well as in receptive‐stage volatiles emitted by two other sympatric fig species, Ficus racemosa and Ficus hispida. 3. Bioassays using the specific pollinator of F. semicordata, Ceratosolen gravelyi, in a Y‐tube olfactometer showed that 4‐methylanisole was attractive to C. gravelyi in a wide range of concentrations (from 1·22 × 10−2 ng/100 μL to 1·22 × 106ng/100μL). Moreover, chemical blends lacking 4‐methylanisole were unattractive to C. gravelyi. These non‐active odour sources included volatile compounds emitted by receptive figs of the two other sympatric fig species and volatiles of F. semicordata post‐pollination figs. 4. All these results suggest that 4‐methylanisole is the main signal compound in the floral scent of F. semicordata that attracts its obligate pollinator to the host figs at the precise stage required for pollination and oviposition. Furthermore, the high proportion of 4‐methylanisole in the odours of receptive figs of both sexes was consistent with the hypothesis of chemical mimicry in dioecious figs. 5. A simple signal comprised of one compound that is unusual among Ficus and that is an infrequent, usually minor, component of other floral odours, may thus function as a private channel in this specialized obligate mutualism.

Effects of extreme variation in female morph frequencies on the mating behaviour of male damselflies

Female-limited polymorphism is often attributed to selection to avoid excessive male mating attempts. It is encountered in various taxonomic groups, but is particularly common in damselflies, where one female morph (andromorph) typically resembles the conspecific male in colour pattern, while the other(s) (gynomorph(s)) do not. Two sets of theories have been proposed to explain the phenomenon in damselflies, which can be classified as the learned mate recognition (LMR) and male mimicry (MM) hypotheses. To test predictions of these hypotheses, we evaluated the rate of male sexual response towards female morphs and conspecific males in the damselfly Nehalennia irene. The LMR hypothesis predicts that males should respond sexually to andromorphs at greater rates in populations containing a higher relative frequency of andromorphs. The MM hypothesis predicts that males respond more often sexually to both andromorphs and males as the ratio of andromorphs to males increases. While LMR predicts that the rate of mating attempts towards gynomorphs should vary, the MM predicts that it should be relatively fixed. On experimentally presenting live specimens to focal males in five different populations with extreme variation in female morph frequencies, we observed that as the andromorph frequency and ratio of andromorphs to males increased, the proportion of male mating attempts increased on both andromorphs and males, whereas it decreased on gynomorphs. While the simplest form of the MM hypothesis is rejected, the results support specific predictions of both hypotheses and suggest that future studies should not treat these hypotheses as mutually exclusive.

Primary biliary cirrhosis, bacteria and molecular mimicry: what's the molecule and where's the mimic?

Primary biliary cirrhosis, bacteria and molecular mimicry: what's the molecule and where's the mimic?

Correlated morphological and colour differences among females of the damselflyIschnura elegans

Abstract1. The female‐limited colour polymorphic damselflyIschnura eleganshas proven to be an interesting study organism both as an example of female sexual polymorphism, and in the context of the evolution of colour polymorphism, as a model of speciation processes.2. Previous research suggests the existence of correlations between colour morph and other phenotypic traits, and the different female morphs inI. elegansmay be pursuing alternative phenotypically integrated strategies. However, previous research on morphological differences in southern Swedish individuals of this species was only carried out on laboratory‐raised offspring from a single population, leaving open the question of how widespread such differences are.3. The present study therefore analysed multi‐generational data from 12 populations, investigating morphological differences between the female morphs in the field, differences in the pattern of phenotypic integration between morphs, and quantified selection on morphological traits.4. It was found that consistent morphological differences indeed existed between the morphs across populations, confirming that the previously observed differences were not simply a laboratory artefact. It was also found, somewhat surprisingly, that despite the existence of sexual dimorphism in body size and shape, patterns of phenotypic integration differed most between the morphs and not between the sexes. Finally, linear selection gradients showed that female morphology affected fecundity differently between the morphs.5. We discuss the relevance of these results to the male mimicry hypothesis and to the existence of potential ecological differences between the morphs.

Severe autoimmune hepatitis triggered by varicella zoster infection

Autoimmune hepatitis (AIH) is a chronic disease of unknown etiology that is characterized by the presence of circulatory autoantibodies and inflammatory histological changes in the liver. Although the pathogenesis of AIH is not known, it is thought that, in a genetically predisposed individual, environmental factors such as viruses can trigger the autoimmune process. Herpes simplex virus, Epstein-Barr virus, measles virus, and hepatitis viruses are thought to play a role in the etiology of AIH. Proteins belonging to these viruses may be similar to the amino acid chains of different autoantigens in the liver, this causes immune cross reactions and liver tissue damage. We report a case of severe AIH following varicella zoster infection in a 23-year-old man, and speculate that, based on the molecular mimicry hypothesis, the liver damage was caused by an immune cross reaction to the viral proteins. Varicella-zoster-induced AIH has not been reported previously.

Support for the nest mimicry hypothesis in Yellow‐rumped Thornbills Acanthiza chrysorrhoa

The nest of the Yellow‐rumped Thornbill Acanthiza chrysorrhoa (endemic to Australia) consists of a lower domed nest where the young are cared for and an upper cup‐shaped structure, referred to as the false nest. Numerous hypotheses have been proposed to explain the primary function of the false nest, but their predictions remain largely untested. Here, we test predictions of the nest mimicry hypothesis (with artificial nests) whereby the empty false nest acts as a decoy, deflecting visual nest predators and/or brood parasites away from the true nest below, thereby increasing nesting success. Clear detection of the false nest by adversaries is an intrinsic aspect of nest mimicry; thus we also test whether conspicuous nests (natural) are favoured by natural selection. Specifically, (1) we compare predation level at artificial domed nests with and without a false nest; and (2) we analyse associations between nest site concealment and nesting outcome in natural nests in a wild population. Supporting the nest mimicry hypothesis, predation level was significantly lower for artificial domed nests with false nests, and for natural nests with lower levels of concealment.

Localization of carbohydrate determinants common toBiomphalaria glabrataas well as to sporocysts and miracidia ofSchistosoma mansoni

The presence of antigenic carbohydrate epitopes shared by Biomphalaria glabrata as well as by the sporocysts and miracidia representing snail-pathogenic larval stages of Schistosoma mansoni was assayed by immunohistochemical staining of paraformaldehyde-fixed tissues. To this end, both polyclonal rabbit antiserum raised against soluble egg antigens (SEA) of S. mansoni and monoclonal antibodies recognizing the carbohydrate epitopes LDN [GalNAc(beta1-4)GlcNAc(beta1-)], F-LDN [Fuc(alpha1-3)GalNAc(beta1-4)GlcNAc(beta1-)], LDN-F [GalNAc(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-)], LDN-DF [GalNAc(beta1-4)[Fuc(alpha1-2)Fuc(alpha1-3)]GlcNAc(beta1-)] and Lewis X [Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-)] were used. Intriguingly, anti-SEA serum as well as anti-F-LDN antibodies displayed significant binding in the foot region, anterior tissue and the hepatopancreas of uninfected snails, whereas the Lewis X epitope was only weakly detectable in the latter tissue. In contrast, increased binding of antibodies recognizing LDN, LDN-F and LDN-DF was observed in infected snail tissue, in particular in regions involved in sporocystogenesis, in addition to an enhanced binding of anti-SEA serum and antibodies reacting with F-LDN. A pronounced expression of most of these carbohydrate antigens was also observed at the surface of miracidia. Hence, the detection of shared carbohydrate determinants in uninfected snail tissue, sporocysts and miracidia may support the hypothesis of carbohydrate-based molecular mimicry as a survival strategy of S. mansoni.

Social Motives Underlying Antisocial Behavior Across Middle School Grades

The goal of the study was to examine whether social motives (social mimicry, mutual attraction, and unreciprocated attraction) predict changes in antisocial behavior across middle school grades. The 2,003 initial participants (55% girls) were drawn from a larger longitudinal study of urban public school students: 44% Latino, 26% African-American, 10% Asian, 9% Caucasian, and 11% multiracial. Analyses of peer nominations and teacher-rated behavior included five waves of data between the fall of sixth grade and the spring of eighth grade (n = 1,260–1,347 for longitudinal analyses). Supporting the social mimicry hypothesis, students who associated peer-directed aggression with high social status in the beginning of middle school engaged in elevated levels of antisocial conduct during the second year in the new school. Additionally, unreciprocated attraction toward peers who bully others in the beginning of middle school was related to increased antisocial behavior in the last year of middle school. No support was obtained for the mutual attraction hypothesis. The findings provide insights about possible social motives underlying susceptibility to negative peer influence.

WHY DOES THE YELLOW-EYED ENSATINA HAVE YELLOW EYES? BATESIAN MIMICRY OF PACIFIC NEWTS (GENUSTARICHA) BY THE SALAMANDERENSATINA ESCHSCHOLTZII XANTHOPTICA

Color patterns commonly vary geographically within species, but it is rare that such variation corresponds with divergent antipredator strategies. The polymorphic salamander Ensatina eschscholtzii, however, may represent such a case. In this species, most subspecies are cryptically colored, whereas E. e. xanthoptica, the Yellow eyed ensatina, is hypothesized to be an aposematic mimic of highly toxic Pacific newts (genus Taricha). To test the mimicry hypothesis, we conducted feeding trials using Western Scrub-Jays, Aphelocoma californica. In every feeding trial, we found that jays, following presentation with the presumed model (T. torosa), were more hesitant to contact the presumed mimic (E. e. xanthoptica) than a control subspecies lacking the postulated aposematic colors (E. e. oregonensis). The median time to contact was 315 sec for the mimic and 52 sec for the control. These results support the mimicry hypothesis, and we suggest that E. e. xanthoptica is likely a Batesian mimic, rather a Müllerian or quasi-Batesian mimic, of Pacific newts.

The effects of delayed plumage maturation on aggression and survival in male red-backed fairy-wrens

The occurrence of multiple phenotypes within a sex of a single species has long puzzled behavioral ecologists. Male red-backed fairy-wrens Malurus melanocephalus exhibit 3 behaviorally distinct types in their first breeding season: breed in bright nuptial plumage, breed in dull plumage, or remain as an unpaired auxiliary (helper) with dull plumage. The retention of dull plumage by auxiliaries and dull breeders is an example of delayed plumage maturation (DPM), a widespread phenomenon in birds whose costs and benefits are not well understood. At a mechanistic level, DPM might allow dull males either to deceptively mimic females (female mimicry hypothesis) or to honestly signal their subordinate status (status-signaling hypothesis). DPM might function via either mechanism to provide ultimate benefits relative to developing nuptial plumage by increasing reproductive success, survival, or both. In this study, we tested the hypothesis that DPM is related to increased male survival in the red-backed fairy-wren via either female mimicry or status signaling. Aviary-based experiments revealed that dull males were perceived as male, which is consistent with the status-signaling hypothesis but contradicts the female mimicry hypothesis. Further aviary and field-based experiments also revealed that dull males were socially subordinate to bright males and received less aggression than bright males, further evidence for status signaling. However, male survival was not related to plumage coloration or breeding status. These findings indicate that male plumage coloration signals social status but that dull plumage does not afford a net survival advantage, perhaps because plumage color is a conditional strategy.

Delayed plumage maturation in Eurasian kestrels: female mimicry, subordination signalling or both?

Delayed plumage maturation (DPM) of young males in sexually dichromatic birds has been explained under the female mimicry hypothesis (FMH) or the subordination signalling hypothesis (SbSH), among other adaptive ideas proposed. In this study, we tested in the Eurasian kestrel, Falco tinnunculus, the predicted sexual deception and aggressiveness under the FMH and SbSH to explain DPM in birds. We analysed aggressive and courtship behaviour of breeding males and females in the presence of adult male, adult female and 1-year-old male natural decoys. We designed two different treatments: one presenting un-moulted 1-year-old males and a second presenting partly moulted 1-year-old males, as observed in nature. Males attacked adult male decoys more frequently than 1-year-old male and female decoys in both moulted and un-moulted treatments and no sexual displays were observed. Females were more aggressive towards female and 1-year-old male decoys as compared to male decoys in the un-moulted treatment. In the moulted treatment, females were more aggressive towards female decoys as compared to both male decoys. In addition, females solicited copulas from moulted, but not from un-moulted, 1-year-old male decoys. Our results suggest that FMH can be a mechanism which explains DPM in un-moulted 1-year-old males. However, when they show moulted plumage (more than 80% in the studied population during the spring), the SbSH seems to be the mechanism that better explains sexual and agonistic behaviour from adults towards 1-year-old males.

A dynamical model of sexual harassment in damselflies and its implications for female-limited polymorphism

Female-limited polymorphism is a widespread phenomenon in damselflies. Typically, one female morph resembles the male (the andromorph), while the alternative morph(s) does not (the gynomorph(s)). Contemporary explanations for the phenomenon vary, but they generally assume that the polymorphism has a risen as a consequence of frequency-dependent selection on females to avoid excessive male harassment. Here, we quantitatively characterise two hypotheses, the learned-mate recognition hypothesis (LMR) and the male mimicry (MM) hypothesis. The LMR proposes that males learn more quickly to attack the more commonly encountered female morph in the population, so that rarer female phenotypes are harassed relatively less. By contrast, the MM proposes that when andromorphs are initially rare compared to males, then they are harassed less than gynomorphs, due to their morphological similarity to males. We present a parameterised dynamical model of the mating system as a way of quantifying the rate of male harassment of females. We then use this information in a multi-generational model that includes selection via the differential harassment of morphs and genetic drift, as well as between-year variability in damselfly density and sex ratio. The proportions of andromorphs at selective equilibria were analytically identified. While both the LMR and the MM versions of the model predict no consistent change in the equilibrium proportion of andromorphic females with increasing damselfly density, only the MM predicts that the equilibrium proportion of andromorphs should increase with sex ratio. Under low harassment rates (e.g. low population densities and/or low male search rates) selection is absent and female morph frequencies are free to drift. The potential applications of this form of dynamical model for other systems involving sexual harassment are discussed.