MobiSeq: De novo SNP discovery in model and non‐model species through sequencing the flanking region of transposable elements

In recent years, the availability of reduced representation library (RRL) methods has catalysed an expansion of genome‐scale studies to characterize both model and non‐model organisms. Most of these methods rely on the use of restriction enzymes to obtain DNA sequences at a genome‐wide level. These approaches have been widely used to sequence thousands of markers across individuals for many organisms at a reasonable cost, revolutionizing the field of population genomics. However, there are still some limitations associated with these methods, in particular the high molecular weight DNA required as starting material, the reduced number of common loci among investigated samples, and the short length of the sequenced site‐associated DNA. Here, we present MobiSeq, a RRL protocol exploiting simple laboratory techniques, that generates genomic data based on PCR targeted enrichment of transposable elements and the sequencing of the associated flanking region. We validate its performance across 103 DNA extracts derived from three mammalian species: grey wolf (Canis lupus), red deer complex (Cervus sp.) and brown rat (Rattus norvegicus). MobiSeq enables the sequencing of hundreds of thousands loci across the genome and performs SNP discovery with relatively low rates of clonality. Given the ease and flexibility of MobiSeq protocol, the method has the potential to be implemented for marker discovery and population genomics across a wide range of organisms—enabling the exploration of diverse evolutionary and conservation questions.     

Multiple stressor effects on coral reef ecosystems

Global climate change has profound implications on species distributions and ecosystem functioning. In the coastal zone, ecological responses may be driven by various biogeochemical and physical environmental factors. Synergistic interactions can occur when the combined effects of stressors exceed their individual effects. The Red Sea, characterized by strong gradients in temperature, salinity, and nutrients along the latitudinal axis provides a unique opportunity to study ecological responses over a range of these environmental variables. Using multiple linear regression models integrating in situ, satellite and oceanographic data, we investigated the response of coral reef taxa to local stressors and recent climate variability. Taxa and functional groups responded to a combination of climate (temperature, salinity, air‐sea heat fluxes, irradiance, wind speed), fishing pressure and biogeochemical (chlorophyll a and nutrients ‐ phosphate, nitrate, nitrite) factors. The regression model for each species showed interactive effects of climate, fishing pressure and nutrient variables. The nature of the effects (antagonistic or synergistic) was dependent on the species and stressor pair. Variables consistently associated with the highest number of synergistic interactions included heat flux terms, temperature, and wind speed followed by fishing pressure. Hard corals and coralline algae abundance were sensitive to changing environmental conditions where synergistic interactions decreased their percentage cover. These synergistic interactions suggest that the negative effects of fishing pressure and eutrophication may exacerbate the impact of climate change on corals. A high number of interactions were also recorded for algae, however for this group, synergistic interactions increased algal abundance. This study is unique in applying regression analysis to multiple environmental variables simultaneously to understand stressor interactions in the field. The observed responses have important implications for understanding climate change impacts on marine ecosystems and whether managing local stressors, such as nutrient enrichment and fishing activities, may help mitigate global drivers of change.     

Nature-inspired pyrrolo[2,3-d]pyrimidines targeting the histamine H3 receptor

Inspired by marine compounds the derivatization of the natural pyrrolo[2,3-d]pyrimidine lead scaffold led to a series of novel compounds targeting the histamine H₃ receptor. The focus was set on improved binding towards the receptor and to establish an initial structure-activity relationship for this compound class based on the lead structure (compound V, K_i value of 126 nM). As highest binding affinities were found with 1,4-bipiperidines as basic part of the ligands, further optimization was focused on 4-([1,4′-bipiperidin]-1′-yl)-pyrrolo[2,3-d]pyrimidines. Related pyrrolo[2,3-d]pyrimidines that were isolated from marine sponges like 4-amino-5-bromopyrrolo[2,3-d]pyrimidine (compound III), showed variations in halogenation pattern, though in a next step the impact of halogenation at 2-position was evaluated. The chloro variations did not improve the affinity compared to the dehalogenated compounds. However, the simultaneous introduction of lipophilic cores with electron-withdrawing substitution patterns in 7-position and dehalogenation at 2-position (11b, 12b) resulted in compounds with significantly higher binding affinities (K_i values of 7 nM and 6 nM, respectively) than the initial lead structure compound V. The presented structures allow for a reasonable structure-activity relationship of pyrrolo[2,3-d]pyrimidines as histamine H₃ receptor ligands and yielded novel lead structures within the natural compound library against this target.     

Exon Inclusion Modulates Conformational Plasticity and Autoinhibition of the Intersectin 1 SH3A Domain

1. Download : Download high-res image (223KB)
2. Download : Download full-size image

     

Inverse electron demand Diels–Alder (IEDDA) reactions in peptide chemistry

Click chemistry is applied to selectively modify, lable and ligate peptides for their use as therapeutics, in biomaterials or analytical investigations. The inverse electron demand Diels‐Alder (IEDDA) reaction is a catalyst‐free click reaction with pronounced chemoselectivity and fast reaction rates. Applications and achievements of the IEDDA reaction in peptide chemistry since 2008 are described in this review.     

Direct and indirect genetic effects on reproductive investment in a grasshopper

A fundamental part of the quantitative genetic theory deals with the partitioning of the phenotypic variance into additive genetic and environmental components. During interaction with conspecifics, the interaction partner becomes a part of the environment from the perspective of the focal individual. If the interaction effects have a genetic basis, they are called indirect genetic effects (IGEs) and can evolve along with direct genetic effects. Sexual reproduction is a classic context where potential conflict between males and females can arise from trade‐offs between current and future investments. We studied five female fecundity traits, egg length and number, egg pod length and number and latency to first egg pod, and estimated the direct and IGEs using a half‐sib breeding design in the grasshopper Chorthippus biguttulus. We found that the male IGEs were an order of magnitude lower than the direct genetic effects and were not significantly different from zero. However, there was some indication that IGEs were larger shortly after mating, consistent with the idea that IGEs fade with time after interaction. Female direct heritabilities were moderate to low. Simulation shows that the variance component estimates can appear larger with less data, calling for care when interpreting variance components estimated with low power. Our results illustrate that the contribution of male IGEs is overall low on the phenotypic variance of female fecundity traits. Thus, even in the relevant context of sexual conflict, the influence of male IGEs on the evolutionary trajectory of female reproductive traits is likely to be small.     

How phenotypic matching based on neutral mating cues enables speciation in locally adapted populations

Maynard Smith's (American Naturalist, 1966, 100, 637) suggestion that in some cases a prerequisite for speciation is the existence of local ecological adaptations has not received much attention to date. Here, we test the hypothesis using a model like that of Maynard Smith but differing in the way animals disperse between niches. In previous studies, males disperse randomly between niches but females stay put in their natal niche. As a first step toward generalizing the model, we here analyze the case that equal proportions of the two sexes disperse between niches before breeding. Supporting Maynard Smith's (1966) hypothesis, we find that once local adaptations are established, a neutral mating cue at an independent locus can rapidly enable speciation in populations with a suitable mechanism for phenotype matching. We find that stable ecological polymorphisms are relatively insensitive to the strength of selection, but depend crucially on the extent of dispersal between niches, with a threshold of ~5% if population sizes in two niches are equal. At higher levels of dispersal, ecological differentiation is lost. These results contrast with those of earlier studies and shed light on why parapatric speciation is limited by the extent of gene flow. Our testable model provides a candidate explanation for the rapid speciation rates, diversity of appearance and occurrence of “species flocks” observed among some African cichlids and neotropical birds and may also have implications for the occurrence of punctuational change on phylogenies.     

Acute Complexin Knockout Abates Spontaneous and Evoked Transmitter Release

1. Download high-res image (151KB)
2. Download full-size image

     

Sequence evolution of the sperm ligand zonadhesin correlates negatively with body weight dimorphism in primates

Sexual selection has repeatedly been shown to be the probable driving force behind the positive Darwinian evolution of genes affecting male reproductive success. Here we compare the sequence evolution of the sperm ligand zonadhesin with body mass dimorphism in primates. In contrast to previous related studies, the present approach takes into account not only catarrhine primates, but also platyrrhines and lemurs. In detail, we analyze the sequence evolution of concatenated zonadhesin fragments (555 bp) of four Lemuroidea, five Platyrrhini, and seven Catarrhini, using the rate ratio of nonsynonymous to synonymous substitutions (dn/ds=omega). Unexpectedly, subsequent regression analyzes between omega estimates for the terminal branches of a primate phylogeny and residual male body mass reveal that sequence evolution of zonadhesin decreases with increasing sexual dimorphism in body weight. Mapping published mating system classifications onto these results illustrates that unimale breeding species show a tendency for rather slow sequence evolution of zonadhesin and comparably pronounced sexual dimorphism in body weight. Female choice and sperm competition can be assumed to drive the evolution of zonadhesin. We speculate that the level of sperm competition is lower in more sexually dimorphic primates because males of these species monopolize access to fertile females more successfully. Thus, variation in sperm competition may be driving the observed negative correlation of sequence evolution and sexual dimorphism in body weight.