Cellular calcium and redox regulation: the mediator of vertebrate environmental sex determination?

Many reptiles and some fish determine offspring sex by environmental cues such as incubation temperature. The mechanism by which environmental signals are captured and transduced into specific sexual phenotypes has remained unexplained for over 50 years. Indeed, environmental sex determination (ESD) has been viewed as an intractable problem because sex determination is influenced by a myriad of genes that may be subject to environmental influence. Recent demonstrations of ancient, conserved epigenetic processes in the regulatory response to environmental cues suggest that the mechanisms of ESD have a previously unsuspected level of commonality, but the proximal sensor of temperature that ultimately gives rise to one sexual phenotype or the other remains unidentified. Here, we propose that in ESD species, environmental cues are sensed by the cell through highly conserved ancestral elements of calcium and redox (CaRe) status, then transduced to activate ubiquitous signal transduction pathways, or influence epigenetic processes, ultimately to drive the differential expression of sex genes. The early evolutionary origins of CaRe regulation, and its essential role in eukaryotic cell function, gives CaRe a propensity to be independently recruited for diverse roles as a ‘cellular sensor’ of environmental conditions. Our synthesis provides the first cohesive mechanistic model connecting environmental signals and sex determination pathways in vertebrates, providing direction and a framework for developing targeted experimentation.     

A comparative view on sex determination in medaka

In fish, an amazing variety of sex determination mechanisms are known, ranging from hermaphroditism to gonochorism and from environmental to genetic sex determination. This makes fish especially suited for studying sex determination from the evolutionary point of view. In several fish groups, different sex determination mechanisms are found in closely related species, and evolution of this process is still ongoing in recent organisms. The medaka (Oryzias latipes) has an XY-XX genetic sex determination system. The Y-chromosome in this species is at an early stage of evolution. The molecular differences between X and Y are only very subtle and the Y-specific segment is very small. The sex-determining region has accumulated duplicated sequences from elsewhere in the genome, leading to recombinational isolation. The region contains a candidate for the male sex-determining gene named dmrt1bY. This gene arose through duplication of an autosomal chromosome fragment of linkage group 9. While all other genes degenerated, dmrt1bY is the only functional gene in the Y-specific region. The duplication leading to dmrt1bY occurred recently during evolution of the genus Oryzias. This suggests that different genes might be the master sex-determining gene in other fish.     

The evolution of environmental and genetic sex determination in fluctuating environments

Twenty years ago, Bulmer and Bull suggested that disruptive selection, produced by environmental fluctuations, can result in an evolutionary transition from environmental sex determination (ESD) to genetic sex determination (GSD). We investigated the feasibility of such a process, using mutation-limited adaptive dynamics and individual-based computer simulations. Our model describes the evolution of a reaction norm for sex determination in a metapopulation setting with partial migration and variation in an environmental variable both within and between local patches. The reaction norm represents the probability of becoming a female as a function of environmental state and was modeled as a sigmoid function with two parameters, one giving the location (i.e., the value of the environmental variable for which an individual has equal chance of becoming either sex) and the other giving the slope of the reaction norm for that environment. The slope can be interpreted as being set by the level of developmental noise in morph determination, with less noise giving a steeper slope and a more switchlike reaction norm. We found convergence stable reaction norms with intermediate to large amounts of developmental noise for conditions characterized by low migration rates, small differential competitive advantages between the sexes over environments, and little variation between individual environments within patches compared to variation between patches. We also considered reaction norms with the slope parameter constrained to a high value, corresponding to little developmental noise. For these we found evolutionary branching in the location parameter and a transition from ESD toward GSD, analogous to the original analysis by Bulmer and Bull. Further evolutionary change, including dominance evolution, produced a polymorphism acting as a GSD system with heterogamety. Our results point to the role of developmental noise in the evolution of sex determination.     

植物性染色体进化及性别决定基因研究进展

植物性染色体起源于1对常染色体, 其在不同雌雄异株植物中多次起源并独立演变, 是研究性染色体起源和进化机制的理想材料。过去的研究在一定程度上阐明了植物性染色体的起源和演化动力; 且性染色体遗传退化、性别决定基因以及剂量补偿效应正逐渐成为研究的热点。近年来, 关于植物性染色体进化及性别决定基因的研究取得了一些重要进展。该文综述了植物性染色体的起源、进化、遗传退化、剂量补偿效应以及性别决定基因等, 并对植物性染色体进化研究发展趋势进行了展望。     

Zebrafish sex determination and differentiation: Involvement of FTZ-F1 genes

Sex determination is the process deciding the sex of a developing embryo. This is usually determined genetically; however it is a delicate process, which in many cases can be influenced by environmental factors. The mechanisms controlling zebrafish sex determination and differentiation are not known. To date no sex linked genes have been identified in zebrafish and no sex chromosomes have been identified. However, a number of genes, as presented here, have been linked to the process of sex determination or differentiation in zebrafish. The zebrafish FTZ-F1 genes are of central interest as they are involved in regulating interrenal development and thereby steroid biosynthesis, as well as that they show expression patterns congruent with reproductive tissue differentiation and function. Zebrafish can be sex reversed by exposure to estrogens, suggesting that the estrogen levels are crucial during sex differentiation. The Cyp19 gene product aromatase converts testosterone into 17 beta-estradiol, and when inhibited leads to male to female sex reversal. FTZ-F1 genes are strongly linked to steroid biosynthesis and the regulatory region of Cyp19 contains binding sites for FTZ-F1 genes, further linking FTZ-F1 to this process. The role of FTZ-F1 and other candidates for zebrafish sex determination and differentiation is in focus of this review.     

From the origin of sex-determining factors to the evolution of sex-determining systems

Sex determination is typically classified as either genotypic or environmental. However, this dichotomy obscures the developmental origin and evolutionary modification of determinants of sex, and therefore hinders an understanding of the processes that generates diversity in sex-determining systems. Recent research on reptiles and fish emphasizes that sex determination is a multifactorial regulatory process that is best understood as a threshold dichotomy rather than as the result of genetically inherited triggers of development. Here we critically assess the relationship between the developmental origin of sex-determining factors and evolutionary transitions in sex-determining systems. Our perspective emphasizes the importance of both genetic and nongenetic causes in evolution of sex determination and may help to generate predictions with respect to the evolutionary patterns of sex-determining systems and the underlying diversity of developmental and genetic regulatory networks.     

Male‐specific alleles in the Ryukyu drywood termite Neotermes sugioi

Sex‐determination systems often show remarkable diversity in upstream signals, although downstream genes are broadly conserved. Therefore, the downstream genes have been investigated in various taxa, but the most upstream signals determining sex in insects have been well‐described mainly in model organisms, including fruit flies and honey bees, and not in hemimetabolous insects such as termites. Identification of sex‐linked genetic markers in termites is important to the survey of primary sex‐determination signals. Here, we report male‐specific alleles at the microsatellite locus NK12‐1 in the Ryukyu drywood termite Neotermes sugioi (Kalotermitidae). This study provides the third example of a genetic marker linked with sexual phenotype in termites, which is a small but important step to elucidate the evolutionary process of the sex‐determination system in termites.     

Evolution of “determinants” in sex-determination: A novel hypothesis for the origin of environmental contingencies in avian sex-bias

Sex-determination is commonly categorized as either “genetic” or “environmental”—a classification that obscures the origin of this dichotomy and the evolution of sex-determining factors. The current focus on static outcomes of sex-determination provides little insight into the dynamic developmental processes by which some mechanisms acquire the role of sex determinants. Systems that combine “genetic” pathways of sex-determination (i.e., sex chromosomes) with “environmental” pathways (e.g., epigenetically induced segregation distortion) provide an opportunity to examine the evolutionary relationships between the two classes of processes and, ultimately, illuminate the evolution of sex-determining systems. Taxa with sex chromosomes typically undergo an evolutionary reduction in size of one of the sex chromosomes due to suppressed recombination, resulting in pronounced dimorphism of the sex chromosomes, and setting the stage for emergence of epigenetic compensatory mechanisms regulating meiotic segregation of heteromorphic sex chromosomes. Here we propose that these dispersed and redundant regulatory mechanisms enable environmental contingency in genetic sex-determination in birds and account for frequently documented context-dependence in avian sex-determination. We examine the evolution of directionality in such sex-determination as a result of exposure of epigenetic regulators of meiosis to natural selection and identify a central role of hormones in integrating female reproductive homeostasis, resource allocation to oocytes, and offspring sex. This approach clarifies the evolutionary relationship between sex-specific molecular genetic mechanisms of sex-determination and non-sex-specific epigenetic regulators of meiosis and demonstrates that both can determine sex. Our perspective shows how non-sex-specific mechanisms can acquire sex-determining function and, by establishing the explicit link between physiological integration of oogenesis and sex-determination, opens new avenues to the studies of adaptive sex-bias and sex-specific resource allocation in species with genetic sex-determination.     

The impact of endosymbionts on the evolution of host sex-determination mechanisms

The past years have revealed that inherited bacterial endosymbionts are important sources of evolutionary novelty for their eukaryotic hosts. In this review we discuss a fundamental biological process of eukaryotes influenced by bacterial endosymbionts: the mechanisms of sex determination. Because they are maternally inherited, several endosymbionts of arthropods, known as reproductive parasites, have developed strategies to convert non-transmitting male hosts into transmitting females through feminization of genetic males and parthenogenesis induction. Recent investigations have also highlighted that endosymbionts can impact upon host sex determination more subtly through genetic conflicts, resulting in selection of host nuclear genes resisting endosymbiont effects. Paradoxically, it is because of their selfish nature that reproductive parasites are such powerful agents of evolutionary change in their host sex-determination mechanisms. They might therefore represent excellent models for studying transitions between sex-determining systems and, more generally, the evolution of sex-determination mechanisms in eukaryotes.     

Temperature-dependent sex determination in reptiles: Proximate mechanisms,ultimate outcomes,and practical applications

In many egg-laying reptiles, the incubation temperature of the egg determines the sex of the offspring, a process known as temperature-dependent sex determination (TSD). In TSD sex determination is an “all or none” process and intersexes are rarely formed. How is the external signal of temperature transduced into a genetic signal that determines gonadal sex and channels sexual development? Studies with the red-eared slider turtle have focused on the physiological, biochemical, and molecular cascades initiated by the temperature signal. Both male and female development are active processes—rather than the crganized/default system characteristic of vertebrates with genotypic sex determination—that require simultaneous activation and suppression of testis- and ovary-determining cascades for normal sex determination. It appears that temperature accomplishes this end by acting on genes encoaing for steroidogenic enzymes and steroid hormone receptors and modifying the endocrine microenvironment in the embryo. The temperature experienced in development also has long-term functional outcomes in addition to sex determination. Research with the leopard gecko indicates that incubation temperature as well as steroid hormones serve as organizers in shaping the adult phenotype, with temperature modulating sex hormone action in sexual differentiation. Finally, practical applications of this research have emerged for the conservation and restoration of endangered egg-laying reptiles as well as the embryonic development of reptiles as biomarkers to monitor the estrogenic effects of common environmental contaminants. © 1994 Wiley-Liss, Inc.     

Genomic conflict in scale insects: the causes and consequences of bizarre genetic systems

It is now clear that mechanisms of sex determination are extraordinarily labile, with considerable variation across all taxonomic levels. This variation is often expressed through differences in the genetic system (XX‐XY, XX‐XO, haplodiploidy, and so on). Why there is so much variation in such a seemingly fundamental process has attracted much attention, with recent ideas concentrating on the possible role of genomic conflicts of interest. Here we consider the role of inter‐ and intra‐genomic conflicts in one large insect taxon: the scale insects. Scale insects exhibit a dizzying array of genetic systems, and their biology promotes conflicts of interest over transmission and sex ratio between male‐ and female‐expressed genes, parental‐ and offspring‐expressed genes (both examples of intra‐genomic conflict) and between scale insects and their endosymbionts (inter‐genomic conflict). We first review the wide range of genetic systems found in scale insects and the possible evolutionary transitions between them. We then outline the theoretical opportunities for genomic conflicts in this group and how these might influence sex determination and sex ratio. We then consider the evidence for these conflicts in the evolution of sex determination in scale insects. Importantly, the evolution of novel genetic systems in scale insects has itself helped create new conflicts of interest, for instance over sex ratio. As a result, a major obstacle to our understanding of the role of conflict in the evolution of sex‐determination and genetic systems will be the difficulty in identifying the direction of causal relationships. We conclude by outlining possible experimental and comparative approaches to test more effectively how important genomic conflicts have been.     

遗传学教学中性别决定关键基因的阐述

有性生殖的出现是生物进化中的重大事件。性别作为生物的一种重要而又复杂的表型, 由基因和环境因素共同控制, 其中遗传因素即基因起到非常关键的作用。 然而, 并不是每个相关基因对于生物的性别都具有相同的作用, 性别决定关键基因对生物性别的决定和性别的分化具有重要作用, 因而研究和理解性别决定的关键基因具有重要意义。随着现代遗传学的发展, 目前关于生物性别决定方式以及性别决定关键基因的研究已取得了很大的进展。文章就生物的基因性别决定机制以及基因性别决定机制的研究策略进行了综述, 以期在遗传学教学中能更好地理解和阐述。     

用模式生物青鳉概观硬骨鱼性别决定及性分化研究进展

鱼类性别决定和性分化呈多元性,既有雌雄同体也有雌雄异体。性腺的雌雄性分化过程受遗传和环境因素(如温度、光照、激素和pH值等)影响,具有可逆可塑性。随着生物技术和基因组学的迅速发展,近年来脊椎动物性别决定和性分化的研究有了重大进展和显著突破。本文通过聚焦青鳉及其他硬骨鱼纲保守存在的dmrt1、gsdf、amh等雄性因子,探讨硬骨鱼普遍存在的雌雄性别可塑可逆信号通路,并介绍了新的基因组编辑和性控育种技术,为单性选育等水产养殖技术的研发提供参考。     

Sex from W to Z: evolution of vertebrate sex chromosomes and sex determining genes

Sex determination in major vertebrate groups appears to be very variable, including systems of male heterogamety, female heterogamety and a variety of genetic and environmental sex determining systems. Yet comparative studies of sex chromosomes and sex determining genes now suggest that these differences are more apparent than real. The sex chromosomes of even widely divergent groups now appear to have changed very little over the last 300+ million years, and even independently derived sex chromosomes seem to have followed the same set of evolutionary rules. The sex determining pathway seems to be extremely conserved, although the control of the genes in this pathway is vested in different elements. We present a scenario for the independent evolution of XY male heterogamety in mammals and ZW female heterogamety in birds and some reptiles. We suggest that sex determining genes can be made redundant, and replaced by control at another step of a conserved sex determining pathway, and how choice of a gene as a sex switch has led to the evolution of new sex chromosome systems. J. Exp. Zool. 290:449-462, 2001.     

Genetics of human aggressive behaviour

A consideration of the evolutionary, physiological and anthropological aspects of aggression suggests that individual differences in such behaviour will have important genetic as well as environmental underpinning. Surveys of the likely pathways controlling the physiological and neuronal processes involved highlight, as obvious targets to investigate, genes implicated in sexual differentiation, anxiety, stress response and the serotonin neurotransmitter pathway. To date, however, association studies on single candidates have provided little evidence for any such loci with a major effect size. This may be because genes do not operate independently, but function against a background in which other genetic and environmental factors are crucial. Indeed, a series of recent studies, particularly concentrating on the serotonin and norepinephrine metabolising enzyme, monoamine oxidase A, has emphasised the necessity of examining gene by environmental interactions if the contributions of individual loci are to be understood. These findings will have major significance for the interpretation and analysis of data from detailed whole genome association studies. Functional imaging studies of genetic variants affecting serotonin pathways have also provided valuable insights into potential links between genes, brain and aggressive behaviour.     

TEMPERATURE‐DEPENDENT TURNOVERS IN SEX‐DETERMINATION MECHANISMS: A QUANTITATIVE MODEL

Sex determination is often seen as a dichotomous process: individual sex is assumed to be determined either by genetic (genotypic sex determination, GSD) or by environmental factors (environmental sex determination, ESD), most often temperature (temperature sex determination, TSD). We endorse an alternative view, which sees GSD and TSD as the ends of a continuum. Both effects interact a priori, because temperature can affect gene expression at any step along the sex‐determination cascade. We propose to define sex‐determination systems at the population‐ (rather than individual) level, via the proportion of variance in phenotypic sex stemming from genetic versus environmental factors, and we formalize this concept in a quantitative‐genetics framework. Sex is seen as a threshold trait underlain by a liability factor, and reaction norms allow modeling interactions between genotypic and temperature effects (seen as the necessary consequences of thermodynamic constraints on the underlying physiological processes). As this formalization shows, temperature changes (due to e.g., climatic changes or range expansions) are expected to provoke turnovers in sex‐ determination mechanisms, by inducing large‐scale sex reversal and thereby sex‐ratio selection for alternative sex‐determining genes. The frequency of turnovers and prevalence of homomorphic sex chromosomes in cold‐blooded vertebrates might thus directly relate to the temperature dependence in sex‐determination mechanisms.     

Aphid wing dimorphisms: linking environmental and genetic control of trait variation

Both genetic and environmental factors underlie phenotypic variation. While research at the interface of evolutionary and developmental biology has made excellent advances in understanding the contribution of genes to morphology, less well understood is the manner in which environmental cues are incorporated during development to influence the phenotype. Also virtually unexplored is how evolutionary transitions between environmental and genetic control of trait variation are achieved. Here, I review investigations into molecular mechanisms underlying phenotypic plasticity in the aphid wing dimorphism system. Among aphids, some species alternate between environmentally sensitive (polyphenic) and genetic (polymorphic) control of wing morph determination in their life cycle. Therefore, a traditional molecular genetic approach into understanding the genetically controlled polymorphism may provide a unique avenue into not only understanding the molecular basis of polyphenic variation in this group, but also the opportunity to compare and contrast the mechanistic basis of environmental and genetic control of similar dimorphisms.     

Drosophila sex combs as a model of evolutionary innovations

The diversity of animal and plant forms is shaped by nested evolutionary innovations. Understanding the genetic and molecular changes responsible for these innovations is therefore one of the key goals of evolutionary biology. From the genetic point of view, the origin of novel traits implies the origin of new regulatory pathways to control their development. To understand how these new pathways are assembled in the course of evolution, we need model systems that combine relatively recent innovations with a powerful set of genetic and molecular tools. One such model is provided by the Drosophila sex comb—a male‐specific morphological structure that evolved in a relatively small lineage related to the model species D. melanogaster. Our extensive knowledge of sex comb development in D. melanogaster provides the basis for investigating the genetic changes responsible for sex comb origin and diversification. At the same time, sex combs can change on microevolutionary timescales and differ spectacularly among closely related species, providing opportunities for direct genetic analysis and for integrating developmental and population‐genetic approaches. Sex comb evolution is associated with the origin of novel interactions between Hox and sex determination genes. Activity of the sex determination pathway was brought under the control of the Hox code to become segment‐specific, while Hox gene expression became sexually dimorphic. At the same time, both Hox and sex determination genes were integrated into the intrasegmental spatial patterning network, and acquired new joint downstream targets. Phylogenetic analysis shows that similar sex comb morphologies evolved independently in different lineages. Convergent evolution at the phenotypic level reflects convergent changes in the expression of Hox and sex determination genes, involving both independent gains and losses of regulatory interactions. However, the downstream cell‐differentiation programs have diverged between species, and in some lineages, similar adult morphologies are produced by different morphogenetic mechanisms. These features make the sex comb an excellent model for examining not only the genetic changes responsible for its evolution, but also the cellular processes that translate DNA sequence changes into morphological diversity. The origin and diversification of sex combs provides insights into the roles of modularity, cooption, and regulatory changes in evolutionary innovations, and can serve as a model for understanding the origin of the more drastic novelties that define higher order taxa.