Modular genetic control of sexually dimorphic behaviors

Sex hormones such as estrogen and testosterone are essential for sexually dimorphic behaviors in vertebrates. However, the hormone-activated molecular mechanisms that control the development and function of the underlying neural circuits remain poorly defined. We have identified numerous sexually dimorphic gene expression patterns in the adult mouse hypothalamus and amygdala. We find that adult sex hormones regulate these expression patterns in a sex-specific, regionally restricted manner, suggesting that these genes regulate sex typical behaviors. Indeed, we find that mice with targeted disruptions of each of four of these genes (Brs3, Cckar, Irs4, Sytl4) exhibit extremely specific deficits in sex specific behaviors, with single genes controlling the pattern or extent of male sexual behavior, male aggression, maternal behavior, or female sexual behavior. Taken together, our findings demonstrate that various components of sexually dimorphic behaviors are governed by separable genetic programs.     

Modular Evolution of the Drosophila Metabolome

Comparative phylogenetic studies offer a powerful approach to study the evolution of complex traits. Although much effort has been devoted to the evolution of the genome and to organismal phenotypes, until now relatively little work has been done on the evolution of the metabolome, despite the fact that it is composed of the basic structural and functional building blocks of all organisms. Here we explore variation in metabolite levels across 50 My of evolution in the genus Drosophila, employing a common garden design to measure the metabolome within and among 11 species of Drosophila. We find that both sex and age have dramatic and evolutionarily conserved effects on the metabolome. We also find substantial evidence that many metabolite pairs covary after phylogenetic correction, and that such metabolome coevolution is modular. Some of these modules are enriched for specific biochemical pathways and show different evolutionary trajectories, with some showing signs of stabilizing selection. Both observations suggest that functional relationships may ultimately cause such modularity. These coevolutionary patterns also differ between sexes and are affected by age. We explore the relevance of modular evolution to fitness by associating modules with lifespan variation measured in the same common garden. We find several modules associated with lifespan, particularly in the metabolome of older flies. Oxaloacetate levels in older females appear to coevolve with lifespan, and a lifespan-associated module in older females suggests that metabolic associations could underlie 50 My of lifespan evolution.     

Optogenetic fUSI for brain-wide mapping of neural activity mediating collicular-dependent behaviors

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

     

Juvenile hormone III produced in male accessory glands of the longhorned beetle,Apriona germari,is transferred to female ovaries during copulation

We report on juvenile hormone (JH) biosynthesis in vitro by male accessory glands (MAGs) in the longhorned beetle, Aprionona germari, accompanied by the transfer of JH from males to females during copulation. JH was extracted from the MAGs and separated by reversed‐phase high‐performance liquid chromatography. JH III was identified as the major JH by gas chromatography–mass spectrometry. A radiochemical assay and a non‐radioactive method were used to measure the in vitro rate of JH biosynthesis by the MAGs. After 4 h of incubation with ³H‐methionine in the medium, the radioactivity in the MAGs substantially increased. In a separate assay, incubation of the MAGs with non‐radioactive methionine for 4 h resulted in a 39% increase in JH III. Seven‐day‐old males were injected with medium 199 containing ³H–methionine and 24 h later they were mated with virgin females. Hemolymph and the MAGs were collected from the mated males and hemolymph, ovaries and eggs were collected from the mated females for assaying radioactive JH. The radioactivity incorporated into JH in the MAGs was transferred to the females during copulation and later transferred into their eggs. Assayed 1 h after copulation, JH III level in the MAGs decreased 42% and the content of JH III in the male hemolymph did not change, whereas the content of JH III in the female hemolymph and ovaries both increased. © 2010 Wiley Periodicals, Inc.     

Modular assembly of genes and the evolution of new functions

Modular assembly of novel genes from existing genes has long been thought to be an important source of evolutionary novelty. Thanks to major advances in genomic studies it has now become clear that this mechanism contributed significantly to the evolution of novel biological functions in different evolutionary lineages. Analyses of completely sequenced bacterial, archaeal and eukaryotic genomes has revealed that modular assembly of novel constituents of various eukaryotic intracellular signalling pathways played a major role in the evolution of eukaryotes. Comparison of the genomes of single-celled eukaryotes, multicellular plants and animals has also shown that the evolution of multicellularity was accompanied by the assembly of numerous novel extracellular matrix proteins and extracellular signalling proteins that are absolutely essential for multicellularity. There is now strong evidence that exon-shuffling played a general role in the assembly of the modular proteins involved in extracellular communications of metazoa. Although some of these proteins seem to be shared by all major groups of metazoa, others are restricted to certain evolutionary lineages. The genomic features of the chordates appear to have favoured intronic recombination as evidenced by the fact that exon-shuffling continued to be a major source of evolutionary novelty during vertebrate evolution.     

RNA-activated protein kinase differentially modulates innate immune response mediated by supraphysiological concentrations of thyroid hormone

Nuclear hormone receptor ligands are known to modulate innate immunity by dampening the immune response induced by pathogens. Here, we report that unlike other ligands, 3,3′,5-triiodo-l-thyronine (T3) induced the type 1 IFN response and expression of IFN-stimulated genes (ISGs). T3 action was found to be significantly amplified at supraphysiological concentrations (SPC) and in combination with double-stranded RNA mimic polyinosinic–polycytidylic acid. Induction by T3 was due to non-genomic mechanisms involving integrin binding, calcium mobilization, and phosphatidyl-inositol 3-kinase–AKT pathways, but was independent of TLR3, RIG-I, and IFN-β1 pathways. Whereas siRNA-induced knockdown of RNA-activated protein kinase (PKR) was found to abrogate the T3-induced expression of select ISGs, expression of other T3-induced ISGs was strongly induced by PKR knockdown, indicating the differential role of PKR in modulating T3 action. Together, we describe a novel role of T3 in modulating the innate immune response and identify the importance of PKR in regulating T3-induced immune activation. These findings have important implications in the basic understanding of the mechanisms of T3 function at SPCs and crosstalk involved in the thyroid hormone function and the innate immune response.     

Comparative study of courtship in twelve phycitine moths (Lepidoptera: Pyralidae)

The courtship behavior of 12 phycitine moths (Lepidoptera: Pyralidae) was studied using frame-by-frame analysis of video recordings. Behavioral transitions during courtship were quantified for selected species and kinematic diagrams of courtship sequences were constructed. Interspecific similarities in courtship behaviors were measured by calculating Euclidean distances between species based on 12 courtship characters and by clustering species according to UPGMA (unweighted pair-group method using arithmetic averages). The resulting phenogram revealed two major behavioral patterns in courtship: (1) interactive and (2) simple. The former was characterized by a complex sequence in which, typically, a male approached a pheromoneemitting female, engaged in a head- to- head posture with the female, and then brought his abdomen over his head and struck the female on the head and thorax. This action brought male abdominal scent structures into close proximity with the female antennae. The male then attempted copulation from the head- to- head position by a dorsolateral thrust of the abdomen toward the female genitalia. Males of these species possessed scent structures located either on the eighth abdominal segment, or in a costal fold of the forewing, or both. Courtship in the second group was much more prosaic. After locating the female by response to her sex pheromone, the male simply attempted copulation by lateral abdominal thrusts under the female wing, without behavioral embellishments. Males of species exhibiting simple courtship had either no scent structures or structures that appeared vestigial. The grouping of species based on courtship characters was poorly correlated with taxonomic relationships, suggesting that the selective pressures governing the evolution and maintenance of courtship and male pheromones were distinct from those involved in the evolution of other morphological characters. While we argue that the primary force molding the evolution of courtship was an adaptive response to interspecific mating mistakes, we do not believe that isolation is brought about by the sequence of courtship behaviors themselves, due to the striking similarity in the sequence across several diverse species. Rather, these behaviors act to deliver more efficiently the male pheromonal message, which mayhave evolved for reproductive isolation.     

The relationship between DRD4 polymorphisms and phenotypic correlations of behaviors in the collared flycatcher

There is increasing evidence that the genetic architecture of exploration behavior includes the dopamine receptor D4 gene (DRD4). Such a link implies that the within‐individual consistency in the same behavior has a genetic basis. Behavioral consistency is also prevalent in the form of between‐individual correlation of functionally different behaviors; thus, the relationship between DRD4 polymorphism and exploration may also be manifested for other behaviors. Here, in a Hungarian population of the collared flycatcher, Ficedula albicollis, we investigate how males with distinct DRD4 genotypes differ in the consistent elements of their behavioral displays during the courtship period. In completely natural conditions, we assayed novelty avoidance, aggression and risk‐taking, traits that were previously shown repeatable over time and correlate with each other, suggesting that they could have a common mechanistic basis. We identified two single‐nucleotide polymorphisms (SNP554 and SNP764) in the exon 3 of the DRD4 gene by sequencing a subsample, then we screened 202 individuals of both sexes for these SNPs. Focusing on the genotypic variation in courting males, we found that “AC” heterozygote individuals at the SNP764 take lower risk than the most common “AA” homozygotes (the “CC” homozygotes were not represented in our subsample of males). We also found a considerable effect size for the relationship between SNP554 polymorphism and novelty avoidance. Therefore, in addition to exploration, DRD4 polymorphisms may also be associated with the regulation of behaviors that may incur fear or stress. Moreover, polymorphisms at the two SNPs were not independent indicating a potential role for genetic constraints or another functional link, which may partially explain behavioral correlations.     

Social behaviors of all-male proboscis monkeys when joined by females

In a riverine forest along the Menanggul River, which is a tributary of the Kinabatangan River, Sabah, Malaysia, I observed an all-male group of proboscis monkey (Nasalis larvatus) consisting of 27–30 (mean: 28.8) individuals. This large size of the all-male group seems to be attributed to habitat fragmentation because of the expansion of oil palm plantations. A few females joined this all-male group. Sub-adult females copulated with subadult or large juvenile males. Since the mean male tenure period of this monkey was estimated to be longer than female maturity, and prematured females might leave their natal one-male groups to avoid inbreeding and temporarily participate in the all-male group where males were permissive to them. Even when females joined this group, no conflicts occurred among males.     

Negative control of BAK1 by protein phosphatase 2A during plant innate immunity

Recognition of pathogen‐associated molecular patterns (PAMPs) by surface‐localized pattern‐recognition receptors (PRRs) activates plant innate immunity, mainly through activation of numerous protein kinases. Appropriate induction of immune responses must be tightly regulated, as many of the kinases involved have an intrinsic high activity and are also regulated by other external and endogenous stimuli. Previous evidences suggest that PAMP‐triggered immunity (PTI) is under constant negative regulation by protein phosphatases but the underlying molecular mechanisms remain unknown. Here, we show that protein Ser/Thr phosphatase type 2A (PP2A) controls the activation of PRR complexes by modulating the phosphostatus of the co‐receptor and positive regulator BAK1. A potential PP2A holoenzyme composed of the subunits A1, C4, and B’η/ζ inhibits immune responses triggered by several PAMPs and anti‐bacterial immunity. PP2A constitutively associates with BAK1 in planta. Impairment in this PP2A‐based regulation leads to increased steady‐state BAK1 phosphorylation, which can poise enhanced immune responses. This work identifies PP2A as an important negative regulator of plant innate immunity that controls BAK1 activation in surface‐localized immune receptor complexes.     

Genetic basis of adaptive evolution of a polyphenism by genetic accommodation

Polyphenisms are evolved adaptations in which a genome produces discrete alternative phenotypes in different environments. In this study, the genetic basis of the evolution of a polyphenism by genetic accommodation was investigated. A polyphenic strain and a monophenic strain of Manduca sexta (L.) were crossed and the F(1) offspring and backcross progeny were analysed. The larval colour polyphenism was found to be regulated by one sex-linked gene of major effect and many smaller effect modifier genes. The finding shows that the mechanism of genetic accommodation relies on genetic changes that are consistent with the current view of the genetic basis of adaptive evolution.     

The genetic basis of evolution, adaptation and speciation

A primary question in biology concerns the genetic basis of the evolution of novel traits, often in response to environmental changes, and how this can subsequently cause species isolation. This topic was the focus of the symposium on the Genetics of Speciation and Evolution at the annual meeting of the Canadian Society for Ecology and Evolution, held in Banff in May 2011. The presentations revealed some of the rapid advances being made in understanding the genetic basis of adaptation and speciation, as well as the elegant interplay between an organism's genetic complement and the environment that organism experiences.     

Disentangling genetic and epigenetic determinants of ultrafast adaptation

A major rationale for the advocacy of epigenetically mediated adaptive responses is that they facilitate faster adaptation to environmental challenges. This motivated us to develop a theoretical–experimental framework for disclosing the presence of such adaptation‐speeding mechanisms in an experimental evolution setting circumventing the need for pursuing costly mutation–accumulation experiments. To this end, we exposed clonal populations of budding yeast to a whole range of stressors. By growth phenotyping, we found that almost complete adaptation to arsenic emerged after a few mitotic cell divisions without involving any phenotypic plasticity. Causative mutations were identified by deep sequencing of the arsenic‐adapted populations and reconstructed for validation. Mutation effects on growth phenotypes, and the associated mutational target sizes were quantified and embedded in data‐driven individual‐based evolutionary population models. We found that the experimentally observed homogeneity of adaptation speed and heterogeneity of molecular solutions could only be accounted for if the mutation rate had been near estimates of the basal mutation rate. The ultrafast adaptation could be fully explained by extensive positive pleiotropy such that all beneficial mutations dramatically enhanced multiple fitness components in concert. As our approach can be exploited across a range of model organisms exposed to a variety of environmental challenges, it may be used for determining the importance of epigenetic adaptation‐speeding mechanisms in general.     

Genomic signatures of local adaptation in the Drosophila immune response

As environments and pathogen landscapes shift, host defenses must evolve to remain effective. Due to this selection pressure, among-species comparisons of genetic sequence data often find immune genes to be among the fastest evolving genes across the genome. The full extent and nature of these immune adaptations, however, remain largely unexplored. In a recent study, we analyzed patterns of selection within distinct components of the Drosophila melanogaster immune pathway. While we found evidence of positive selection within some immune processes, immune genes were not universally characterized by signatures of strong selection. On the contrary, we even found that some immune functions show greater than expected constraint. Overall these results highlight 2 major factors that appear to play an outsize role in determining a gene's evolutionary rate: the type of pathogen the gene targets and the gene's position within the immune network. These results join a growing body of literature that highlight the complexity of immune adaptation. Rather than there being uniformly strong selection across all immune genes, a combination of pathogen-specificity and host genetic constraints appear to play key roles in determining each immune gene's individual evolutionary trajectory.     

Cloning of a polymorphic canine genetic marker which maps to human chromosome 9

We describe the cloning of a novel canine polymorphic genetic marker which maps to human chromosome 9. The sequence is 2092 bp, 59% GC rich, and contains three GC boxes. Chemilumin-escent probing of zooblots showed evolutionary conservation. Dogs have three Bam HI alleles: 2.3 kb, 2.1 kb and 1.7 kb. Allele frequencies in 17 unrelated dogs representing 13 breeds are presented. Polymorphism for the 1.7-kb allele in beagles is common. The 2.1-kb allele is probably the ancestral allele since it is the most common and is also noted in the Cape hunting dog. Interestingly, in more than 50 dogs tested to date, the 2.3-kb allele has been found only in miniature and giant schnauzers. This points to a common origin for these two breeds.     

Hybridization effects and genetic diversity of the common and black‐tufted marmoset (Callithrix jacchus and Callithrix penicillata) mitochondrial control region

Hybridization is continually documented in primates, but effects of natural and anthropogenic hybridization on biodiversity are still unclear and differentiating between these contexts remains challenging in regards to primate evolution and conservation. Here, we examine hybridization effects on the mitochondrial DNA (mtDNA) control region of Callithrix marmosets, which provide a unique glimpse into interspecific mating under distinct anthropogenic and natural conditions. DNA was sampled from 40 marmosets along a 50‐km transect from a previously uncharacterized hybrid zone in NE Brazil between the ranges of Callithrix jacchus and Callithrix penicillata. DNA was also collected from 46 marmosets along a 30‐km transect in a hybrid zone in Rio de Janeiro state, Brazil, where exotic marmosets appeared in the 1980s. Combining Callithrix DNA sampled inside and outside of these hybrid zones, phylogenetic and network analyses show C. jacchus and C. penicillata being parental species to sampled hybrids. We expand limited Callithrix population genetics work by describing mtDNA diversity and demographic history of these parental species. We show ancient population expansion in C. jacchus and historically constant population size in C. penicillata, with the latter being more genetically diverse than the former. The natural hybrid zone contained higher genetic diversity relative to the anthropogenic zone. While our data suggest hybrid swarm formation within the anthropogenic zone due to removed physical reproductive barriers, this pattern is not seen in the natural hybrid zone. These results suggest different genetic dynamics within natural and anthropogenic hybridization contexts that carry important implications for primate evolution and conservation. Am J Phys Anthropol 155:522–536, 2014. © 2014 Wiley Periodicals, Inc.     

Genetic control of early stages of leaf development

The results of studies of genetic regulation of the early leaf morphogenesis, demarcation of the future primordium and transition of cells to determination, have been reviewed. The genetic systems of control of these developmental stages were shown to be conservative and hypotheses of possible mechanisms underlying the evolution of leaf morphology on their basis have been considered.