Toxicogenomic Analysis Suggests Chemical-Induced Sexual Dimorphism in the Expression of Metabolic Genes in Zebrafish Liver

Differential gene expression in two sexes is widespread throughout the animal kingdom, giving rise to sex-dimorphic gene activities and sex-dependent adaptability to environmental cues, diets, growth and development as well as susceptibility to diseases. Here, we present a study using a toxicogenomic approach to investigate metabolic genes that show sex-dimorphic expression in the zebrafish liver triggered by several chemicals. Our analysis revealed that, besides the known genes for xenobiotic metabolism, many functionally diverse metabolic genes, such as ELOVL fatty acid elongase, DNA-directed RNA polymerase, and hydroxysteroid dehydrogenase, were also sex-dimorphic in their response to chemical treatments. Moreover, sex-dimorphic responses were also observed at the pathway level. Pathways belonging to xenobiotic metabolism, lipid metabolism, and nucleotide metabolism were enriched with sex-dimorphically expressed genes. We also observed temporal differences of the sex-dimorphic responses, suggesting that both genes and pathways are differently correlated during different periods of chemical perturbation. The ubiquity of sex-dimorphic activities at different biological hierarchies indicate the importance and the need of considering the sex factor in many areas of biological researches, especially in toxicology and pathology.     

斑腿泛树蛙两性异形和雌性繁殖能力及其影响因素

研究两栖类物种雌雄间的形态差异,不仅有助于理解物种两性异形的模式与机制,而且对其繁殖策略、繁殖投入和进化选择压力的研究都具有重要意义。2020年4月至2021年8月以浙江省丽水市丽水学院校园永久池塘内的斑腿泛树蛙（Polypedates megacephalus）为实验对象,共61只（♀12,♂49）,测量其头体长、头长、吻宽、前肢长、后肢长等12项形态特征及体重来研究该物种的两性异形,并收集窝卵数和孵化数据分析雌性繁殖能力。结果表明：斑腿泛树蛙具有显著的两性异形,且雌性个体大于雄性个体;眼径、胫长和鼻间距在两性间无显著差异,头体长、头长、吻宽、吻长、眼间距、前肢长、后肢长、前臂及手长、足长和体重均具有显著差异;斑腿泛树蛙雌性个体产卵和孵化率受季节影响显著,其中4和5月窝卵数最多,6月卵孵化率最高;雌性怀卵数量与体长呈正相关关系。依据上述结果,本研究推测生育力选择是造成斑腿泛树蛙两性异形的主要因素,雌性个体通过增大个体体型来增加怀卵量,从而提高繁殖输出;斑腿泛树蛙繁殖期受季节影响,为更好地适应雨季的提前或推迟,在进化过程中形成了延长式繁殖的模式。     

Disentangling the Size and Shape Components of Sexual Dimorphism

Evolutionary Biology - Many organisms are sexually dimorphic, reflecting sex-specific selection pressures. But although sexual dimorphism may consist of different variables from size to shape and...     

A Plasmodium Phospholipase Is Involved in Disruption of the Liver Stage Parasitophorous Vacuole Membrane

The coordinated exit of intracellular pathogens from host cells is a process critical to the success and spread of an infection. While phospholipases have been shown to play important roles in bacteria host cell egress and virulence, their role in the release of intracellular eukaryotic parasites is largely unknown. We examined a malaria parasite protein with phospholipase activity and found it to be involved in hepatocyte egress. In hepatocytes, Plasmodium parasites are surrounded by a parasitophorous vacuole membrane (PVM), which must be disrupted before parasites are released into the blood. However, on a molecular basis, little is known about how the PVM is ruptured. We show that Plasmodium berghei phospholipase, PbPL, localizes to the PVM in infected hepatocytes. We provide evidence that parasites lacking PbPL undergo completely normal liver stage development until merozoites are produced but have a defect in egress from host hepatocytes. To investigate this further, we established a live-cell imaging-based assay, which enabled us to study the temporal dynamics of PVM rupture on a quantitative basis. Using this assay we could show that PbPL-deficient parasites exhibit impaired PVM rupture, resulting in delayed parasite egress. A wild-type phenotype could be re-established by gene complementation, demonstrating the specificity of the PbPL deletion phenotype. In conclusion, we have identified for the first time a Plasmodium phospholipase that is important for PVM rupture and in turn for parasite exit from the infected hepatocyte and therefore established a key role of a parasite phospholipase in egress.     

The Dilemma of Choosing a Reference Character for Measuring Sexual Size Dimorphism,Sexual Body Component Dimorphism,and Character Scaling: Cryptic Dimorphism and Allometry in the Scorpion Hadrurus arizonensis

Sexual differences in morphology, ranging from subtle to extravagant, occur commonly in many animal species. These differences can encompass overall body size (sexual size dimorphism, SSD) or the size and/or shape of specific body parts (sexual body component dimorphism, SBCD). Interacting forces of natural and sexual selection shape much of the expression of dimorphism we see, though non-adaptive processes may be involved. Differential scaling of individual features can result when selection favors either exaggerated (positive allometry) or reduced (negative allometry) size during growth. Studies of sexual dimorphism and character scaling rely on multivariate models that ideally use an unbiased reference character as an overall measure of body size. We explored several candidate reference characters in a cryptically dimorphic taxon, Hadrurus arizonensis. In this scorpion, essentially every body component among the 16 we examined could be interpreted as dimorphic, but identification of SSD and SBCD depended on which character was used as the reference (prosoma length, prosoma area, total length, principal component 1, or metasoma segment 1 width). Of these characters, discriminant function analysis suggested that metasoma segment 1 width was the most appropriate. The pattern of dimorphism in H. arizonensis mirrored that seen in other more obviously dimorphic scorpions, with static allometry trending towards isometry in most characters. Our findings are consistent with the conclusions of others that fecundity selection likely favors a larger prosoma in female scorpions, whereas sexual selection may favor other body parts being larger in males, especially the metasoma, pectines, and possibly the chela. For this scorpion and probably most other organisms, the choice of reference character profoundly affects interpretations of SSD, SBCD, and allometry. Thus, researchers need to broaden their consideration of an appropriate reference and exercise caution in interpreting findings. We highly recommend use of discriminant function analysis to identify the least-biased reference character.     

Gonadal Dysgenesis Reveals Sexual Dimorphism in the Embryonic Germline of Drosophila

In hybrid dysgenesis, sterility can occur in both males and females. At 27.5 degrees, however, we found that P element-induced germline death was restricted to females. This sex-specific gonadal dysgenesis (GD) is complete by the first larval instar stage. As such, GD at 27.5 degrees reveals the sexually dimorphic character of the embryonic germline. The only other known dimorphic trait of the embryonic germline is the requirement for ovo. ovo is required for germline development in females only and has been implicated in germline sex determination. Dominant mutations of ovo partially suppressed female GD. Although embryonic germ cells are undifferentiated and morphologically indistinguishable between males and females, the functional dimorphism seen in ovo requirement and GD at 27.5 degrees indicates that sexual identity in Drosophila germ cells is established in embryogenesis.     

Identification of Genetic Determinants of the Sexual Dimorphism in CNS Autoimmunity

Multiple sclerosis (MS) is a debilitating chronic inflammatory disease of the nervous system that affects approximately 2.3 million individuals worldwide, with higher prevalence in females, and a strong genetic component. While over 200 MS susceptibility loci have been identified in GWAS, the underlying mechanisms whereby they contribute to disease susceptibility remains ill-defined. Forward genetics approaches using conventional laboratory mouse strains are useful in identifying and functionally dissecting genes controlling disease-relevant phenotypes, but are hindered by the limited genetic diversity represented in such strains. To address this, we have combined the powerful chromosome substitution (consomic) strain approach with the genetic diversity of a wild-derived inbred mouse strain. Using experimental allergic encephalomyelitis (EAE), a mouse model of MS, we evaluated genetic control of disease course among a panel of 26 consomic strains of mice inheriting chromosomes from the wild-derived PWD strain on the C57BL/6J background, which models the genetic diversity seen in human populations. Nineteen linkages on 18 chromosomes were found to harbor loci controlling EAE. Of these 19 linkages, six were male-specific, four were female-specific, and nine were non-sex-specific, consistent with a differential genetic control of disease course between males and females. An MS-GWAS candidate-driven bioinformatic analysis using orthologous genes linked to EAE course identified sex-specific and non-sex-specific gene networks underlying disease pathogenesis. An analysis of sex hormone regulation of genes within these networks identified several key molecules, prominently including the MAP kinase family, known hormone-dependent regulators of sex differences in EAE course. Importantly, our results provide the framework by which consomic mouse strains with overall genome-wide genetic diversity, approximating that seen in humans, can be used as a rapid and powerful tool for modeling the genetic architecture of MS. Moreover, our data represent the first step towards mechanistic dissection of genetic control of sexual dimorphism in CNS autoimmunity.     

Disruption of Daily Rhythms by High-Fat Diet Is Reversible

In mammals a network of circadian clocks coordinates behavior and physiology with 24-h environmental cycles. Consumption of high-fat diet disrupts this temporal coordination by advancing the phase of the liver molecular clock and altering daily rhythms of eating behavior and locomotor activity. In this study we sought to determine whether these effects of high-fat diet on circadian rhythms were reversible. We chronically fed mice high-fat diet and then returned them to low-fat chow diet. We found that the phase of the liver PERIOD2::LUCIFERASE rhythm was advanced (by 4h) and the daily rhythms of eating behavior and locomotor activity were altered for the duration of chronic high-fat diet feeding. Upon diet reversal, the eating behavior rhythm was rapidly reversed (within 2 days) and the phase of the liver clock was restored by 7 days of diet reversal. In contrast, the daily pattern of locomotor activity was not restored even after 2 weeks of diet reversal. Thus, while the circadian system is sensitive to changes in the macronutrient composition of food, the eating behavior rhythm and liver circadian clock are specifically tuned to respond to changes in diet.     

Sexual Dimorphism of Mate Location in the Long-Toed Salamander Ambystoma macrodactylum columbianum

In breeding systems characterized by scramble competition among males, theory predicts that the efficient location of mating partners is more important to males than to females as a component of mating success. We experimentally tested in the laboratory the hypothesis that breeding male long-toed salamanders ( Ambystoma macrodactylum columbianum ), which scramble for mating opportunities, are better able to recognize and locate potential mates than are breeding females. Males were more likely to enter traps containing females than empty traps or traps containing males. Traps containing sponges soiled by females were more likely to attract males than traps containing clean (control) sponges, suggesting that chemical cues may be sufficient for mate location by males. Females were no more likely to enter traps containing males than empty traps. Our results are consistent with the theoretical prediction that selection has been stronger on male long-toed salamanders than on females in the context of capacity for recognizing and locating potential mating partners.     

Evolution of Sexual Size Dimorphism in a Frog Obeys the Inverse of Rensch’s Rule

Rensch’s rule refers to a pattern in sexual size dimorphism (SSD) in which SSD increases with body size when males are the larger sex and decreases with body size when females are the larger sex. Using data on body size from 40 populations and age from 31 populations of the rice frog Rana limnochari with female-biased size dimorphism, I tested the consistency of allometric relationships between males and females with Rensch’s rule and evaluated the hypothesis that SSD was largely a function of age differences between the sexes. Statistical comparisons of body sizes between the sexes showed the evidence for the inverse of Rensch’s rule, indicating the level of SSD increased with increasing mean body size. One of the explanations for the occurrence of the inverse of Rensch’s rule may be the fecundity selection hypothesis assuming increased reproductive output in large females. However, differences in age between males and females among populations could explain mildly the variation in SSD.     

太行山猕猴肩胛骨和肱骨的性别判别

测量了 2 6例 (♀ 1 6,♂ 1 0 )成年太行山猕猴肩胛骨和肱骨的 1 5项变量。通过运用SPSS1 0 0单因子方差分析 ,结果显示 ,有 9项变量在两性间达到了显著差异水平 ;采用多变量判别分析方法对有关变量建立判别函数 ,结果显示 ,采用强迫引入法和逐步判别法 ,判别正确率分别为 1 0 0 0 0 %和 92 3 0 %;运用主成分分析 ,进一步说明肩胛骨和肱骨在性别判别中有一定的作用     

Sexual Size Dimorphism in the Color Pattern Elements of Two Mimetic Heliconius Butterflies

Sexual dichromatism and sexual dimorphism of body size are reasonably well studied in butterflies. Sexual size dimorphism of color pattern elements, however, is much less explored. The object of this study is Heliconius, a genus of butterflies well known for the coevolution between mate color preferences and mimicry. Given the sexual role of wing coloration, we investigated the existence of sexual size dimorphism in the wing color elements of a mimetic pair—Heliconius erato phyllis Fabricius and Heliconius besckei Ménétriés—and analyzed the allometric patterns of these traits. Correlation between size of elements in the dorsal and ventral wing surfaces were also estimated. In both species, three out of four elements were larger in males, but the non-dimorphic element was not the same. With regard to the allometric patterns, our most important finding was that smaller males of one species have proportionally larger yellow bars. This is the first study specifically concerning quantitative sexual dimorphism in the coloration of this well-known genus of butterflies and it opens new prospects to investigate sex-related natural selection and sexual selection of color pattern elements.     

Differential Migration by Sex in the Great Bustard: Possible Consequences of an Extreme Sexual Size Dimorphism

We explored migration patterns in Great bustards ( Otis tarda ), a species that shows strong sexual selection and the most extreme sexual size dimorphism among birds. The aim was to explain differential migration, examining whether Great bustards fulfil the main predictions of bird migration theory hypotheses and sexual segregation theory hypotheses. We radio-tracked the seasonal movements of 65 males and 68 females in central Spain. We found four main sexual differences. First, the proportion of migratory males was higher than that of migratory females (86% vs. 51%). Second, males abandoned the leks immediately after the mating season (late May to early Jun.), whereas females remained there for another 3–7 mo. Third, 54% of the migratory males used two different post-breeding areas, the first located northwards at 82 km from the breeding sites in summer, and the second southwards at 50 km in autumn–winter. Migratory females used only one area in autumn–winter which coincided geographically with that of males. And fourth, males returned to the breeding areas earlier (between Sep. and Mar.) than females (between Jan. and Apr.). These results show that the Great bustard is a differential migrant by sex in central Spain and support the weather sensitivity hypothesis (males were less tolerant to summer heat) and the specialization hypothesis (exclusive maternal care of the brood by females). Sexual differences in migratory behaviour are probably ultimately determined by the strong sexual selection in this species.