Frequent independent origins of environmental sex determination (ESD) are assumed within amniotes. However, the phylogenetic distribution of sex‐determining modes suggests that ESD is likely very ancient and may be homologous across ESD groups. Sex chromosomes are demonstrated to be old and stable in endothermic (mammals and birds) and many ectothermic (non‐avian reptiles) lineages, but they are mostly non‐homologous between individual amniote lineages. The phylogenetic pattern may be explained by ancestral ESD with multiple transitions to later evolutionary stable genotypic sex (...) determination. It is pointed out here that amniote ESD shares several key aspects with sequential hermaphroditism of fishes such as a lack of sex differences in genomes, biased population sex ratios, and potentially also molecular mechanism related to general stress responses. Here, it is speculated that ESD evolves via a heterochronic shift of the sensitive period of sex change from the adult to the embryonic stage in a hermaphroditic amniote ancestor. Also see the video abstract here https://youtu.be/q2mjtlCefu4. (shrink)

Sex reversal, a mismatch between phenotypic and genetic sex, can be induced by chemical and thermal insults in ectotherms. Therefore, climate change and environmental pollution may increase sex‐reversal frequency in wild populations, with wide‐ranging implications for sex ratios, population dynamics, and the evolution of sex determination. We propose that reconsidering the half‐century old theory “Witschi's rule” should facilitate understanding the differences between species in sex‐reversal propensity and thereby predicting their vulnerability to anthropogenic environmental change. The idea is that sex (...) reversal should be asymmetrical: more likely to occur in the homogametic sex, assuming that sex‐reversed heterogametic individuals would produce new genotypes with reduced fitness. A review of the existing evidence shows that while sex reversal can be induced in both homogametic and heterogametic individuals, the latter seem to require stronger stimuli in several cases. We provide guidelines for future studies on sex reversal to facilitate data comparability and reliability. (shrink)

Sex‐determining factors are usually assumed to be either genetic or environmental. The present paper aims at drawing attention to the potential contribution of developmental noise, an important but often‐neglected component of phenotypic variance. Mutual inhibitions between male and female pathways make sex a bistable equilibrium, such that random fluctuations in the expression of genes at the top of the cascade are sufficient to drive individual development toward one or the other stable state. Evolutionary modeling shows that stochastic sex determinants should (...) resist elimination by genetic or environmental sex determinants under ecologically meaningful settings. On the empirical side, many sex‐determination systems traditionally considered as environmental or polygenic actually provide evidence for large components of stochasticity. In reviewing the field, I argue that sex‐determination systems should be considered within a three‐ends continuum, rather than the classical two‐ends continuum. (shrink)

Sex‐determining mechanisms appear to be very diverse in invertebrates. Haplodiploidy is a widespread mode of reproduction in insects: males are haploid and females are diploid. Several models have been proposed for the genetic mechanisms of sex determination in haplodiploid Hymenoptera. Although a one‐locus multi‐allele model is valid for several species, sex determination in other species cannot be explained by any of the existing models. Evidence for and predictions of two recently proposed models are discussed. Some genetic and molecular (...) approaches are proposed to study sex determination in Hymenoptera. (shrink)

For many species that reproduce sexually, how sex is expressed at different points across lifespan is highly contingent and dependent on various environmental factors. For example, in many species of fish, environmental cues can trigger a natural process of sex transition where a female transitions to male. For many species of turtle, incubation temperature influences the likelihood that turtle eggs will hatch males or females. What is the case for Homo sapiens? Is human sex expression influenced by contingent environmental factors (...) like we see in fish and turtles, with whom we share common ancestry and DNA? Our paper explores the current biological science of sex determination and how it applies to philosophical and theological accounts of the human person. We argue that while human sex determination is not susceptible to environmental cues to the same degree we see in other species, there is sufficient variability among the pathways of human sex development to complicate simplistic biological categories of male and female. (shrink)

Not all vertebrates share the familiar system of XX:XY sex determination seen in mammals. In the chicken and other birds, sex is determined by a ZZ:ZW sex chromosome system. Gonadal development in the chicken has provided insights into the molecular genetics of vertebrate sex determination and how it has evolved. Such comparative studies show that vertebrate sex‐determining pathways comprise both conserved and divergent elements. The chicken embryo resembles lower vertebrates in that estrogens play a central role in gonadal (...) sex differentiation. However, several genes shown to be critical for mammalian sex determination are also expressed in the chicken, but their expression patterns differ, indicating functional plasticity. While the genetic trigger for sex determination in birds remains unknown, some promising candidate genes have recently emerged. The Z‐linked gene, DMRT1, supports the Z‐dosage model of avian sex determination. Two novel W‐linked genes, ASW and FET1, represent candidate female determinants. BioEssays 26:120–132, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The pathway that controls sexual fate in the nematode Caenorhabditis elegans has been well characterized at the molecular level. By identifying differences between the sex‐determination mechanisms in C. elegans and other nematode species, it should be possible to understand how complex sex‐determining pathways evolve. Towards this goal, orthologues of many of the C. elegans sex regulators have been isolated from other members of the genus Caenorhabditis. Rapid sequence evolution is observed in every case, but several of the orthologues appear (...) to have conserved sex‐determining roles. Thus extensive sequence divergence does not necessarily coincide with changes in pathway structure, although the same forces may contribute to both. This review summarizes recent findings and, with reference to results from other animals, offers explanations for why sex‐determining genes and pathways appear to be evolving rapidly. Experimental strategies that hold promise for illuminating pathway differences between nematodes are also discussed. BioEssays 25: 221–231, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

In mammals, the Y chromosome induces testis formation and thus male sexual development; in the absence of a Y chromosome, gonads differentiate into ovaries and female development ensues. Molecular genetic studies have identified the Y‐located testis determining gene SRY as well as autosomal and X‐linked genes necessary for gonadal development. The phenotypes resulting from mutation of these genes, together with their patterns of expression, provide the basis for establishing a hierachy of genes and their interactions in the mammalian sex (...) class='Hi'>determination pathway. (shrink)

Recent molecular studies of mammalian sexual determination have been focused on gene expression in the gonadal ridge at the time of appearance of sexual dimorphism: the critical time defined by the ‘Jost principle’. Three lines of evidence suggest that, instead, sex determination may start shortly after conception: (1) the XY preimplantation embryo usually develops more rapidly than the XX preimplantation embryo (this phenotype has been linked to the Y chromosome and will be termed ‘Growth factor Y’); (2) the (...) gene for testis determination, SRY/Sry, and the closely linked genes ZFY/Zfy and Smcy, are transcribed in the preimplantation embryo; and (3) male and female preimplantation embryos are antigenically distinguishable, indicating sex differences in gene expression. The data to support these assertions are reviewed. Possible relationships of these three phenomena to each other and to sex differentiation are discussed. Similarities in mechanisms of sexual determination between marsupial and eutherian mammals are hypothesized. Problems with interpreting male sexual differentiation as being solely due to testosterone and Müllerian inhibiting substance (MIS) are discussed. (shrink)

Endosymbiotic bacteria can directly manipulate their host's sex determination towards the production of female offspring.

Analysis of the mechanisms underlying sex determination and sex differentiation in Drosophila has provided evidence for a complex but comprehensible regulatory hierarchy governing these developmental decisions. It is suggested here that the pattern of sexual differentiation and dosage compensation characteristic of the male is a default regulatory state. Recent results have provided, in addition, some surprising and intriguing conclusions: (1) that several of the critical controlling genes produce more transcripts than was predicted from the genetic analyses; (2) that setting (...) of the alternative sex‐specific states of the doublesex (dsx) locus involves differential transcript processing; and (3) that some aspects of sexual differentation require the prolonged action of certain elements of the regulatory hierarchy. These findings are discussed in connection with the current model of sex determination in Drosophila. (shrink)

Different animal groups exhibit a surprisingly diversity of sex determination systems. Moreover, even systems that are superficially similar may utilize different underlying mechanisms. This diversity is illustrated by a comparison of sex determination in three well‐studied model organisms: the fruitfly Drosophila melanogaster, the nematode Caenorhabditis elegans, and the mouse. All three animals exhibit male heterogamety, extensive sexual dimorphism and sex chromosome dosage compensation, yet the molecular and cellular processes involved are now known to be quite unrelated. The similarities (...) must have arisen by convergent evolution. Studies of sex determination demonstrate that evolution can produce a variety of solutions to the same basic problems in development. (shrink)

Sex chromosomes can differ between species as a result of evolutionary turnover, a process that can be driven by evolution of the sex determination pathway. Canonical models of sex chromosome turnover hypothesize that a new master sex determining gene causes an autosome to become a sex chromosome or an XY chromosome pair to switch to a ZW pair (or vice versa). Here, a novel paradigm for the evolution of sex determination and sex chromosomes is presented, in which there (...) is an evolutionary transition in the master sex determiner, but the X chromosome remains unchanged. There are three documented examples of the novel paradigm, and it is hypothesized that a similar process could happen in a ZW sex chromosome system. Three other taxa are also identified where the novel paradigm may have occurred, and how it could be distinguished from canonical trajectories in these and additional taxa is also described. (shrink)

Sex chromosomes in plants have been known for a century, but only recently have we begun to understand the mechanisms behind sex determination in dioecious plants. Here, we discuss evolution of sex determination, focusing on Silene latifolia, where evolution of separate sexes is consistent with the classic “two mutations” model—a loss of function male sterility mutation and a gain of function gynoecium suppression mutation, which turned an ancestral hermaphroditic population into separate males and females. Interestingly, the gynoecium suppression (...) function in S. latifolia evolved via loss of function in at least two sex‐linked genes and works via gene dosage balance between sex‐linked, and autosomal genes. This system resembles X/A‐ratio‐based sex determination systems in Drosophila and Rumex, and could represent a steppingstone in the evolution of X/A‐ratio‐based sex determination from an active Y system. (shrink)

Sex is determined by non‐Mendelian genetic elements overriding the sex factors carried by the heterochromosomes in some species of terrestrial isopods. A bacterium Wolbachia and a non‐bacterial feminizing factor (f) can both force chromosomal males of Armadillidium vulgare to become phenotypic functional females. The f factor is believed to be a genetic element derived from the Wolbachia genome that becomes inserted into the host nuclear genome. The feminizing factors can be considered to be selfish genetic elements because they bias their (...) host's sex ratio to increase their own transmission. New sex‐determining genes are selected (genes resisting the feminizing effects, or the transmission of feminizing elements) as a consequence of the conflict between these elements and the rest of the host's genome. These events drive the sex‐determining mechanisms to evolve, and may explain the polymorphism of sex factors and the poor differentiation of the heterochromosomes in isopods. (shrink)

The adaptive significance of temperature‐dependent sex determination (TSD) in reptiles remains unknown decades after TSD was first identified in this group. Concurrently, there is growing concern about the effect that rising temperatures may have on species with TSD, potentially producing extremely biased sex ratios or offspring of only one sex. The current state‐of the‐art in TSD research on sea turtles is reviewed here and, against current paradigm, it is proposed that TSD provides an advantage under warming climates. By means (...) of coadaptation between early survival and sex ratios, sea turtles are able to maintain populations. When offspring survival declines at high temperatures, the sex that increases future fecundity (females) is produced, increasing resilience to climate warming. TSD could have helped reptiles to survive mass extinctions in the past via this model. Flaws in research on sex determination in sea turtles are also identified and it is suggested that the development of new techniques will revolutionize the field. (shrink)

In many species of reptiles, sex is determined at fertilization by zygotic sex chromosome composition. In other species, including all crocodilians, most turtles and some lizards, sex is determined by temperature during the earlier stages of gonadal differentiation. The effects of exogenous estrogens, antiestrogens and aromatase inhibitors at different temperatures have unambiguously demonstrated the involvement of estrogens in sexual differentiation of the gonads. Aromatase is the enzyme that converts androgens to estrogens. Gonadal aromatase activity is well correlated with gonadal structure. (...) It increases exponentially in differentiating ovaries, whereas it remains low in differentiating testes. Moreover, there is a high correlation between the thermosensitive periods for both ovary differentiation and increase in aromatase activity. We suggest that a thermosensitive factor intervenes, directly or indirectly, in the transcriptional regulation of the aromatase gene in reptiles with temperature‐dependent sex determination. (shrink)

Prenatal diagnostic technologies have been used for the purpose of detecting sex—leading to abortion of female fetuses—and have posed new challenges to the already difficult question of social justice for women in India. This article reports findings from a case study conducted with 25 women who had used prenatal diagnostic technologies for sex determination.Against the common belief that Indian society is “improving” because of 21st-century medical technology, this case study shows that the social context has given a patriarchal value (...) to such advanced technology in India. Furthermore, it sheds light on why prenatal diagnostic technologies have taken a different route in India.It shows that reasons for accepting the use of prenatal diagnostic technologies for sex determination by women are diverse and complex. (shrink)

Different animal groups exhibit a surprisingly diversity of sex determination systems. Moreover, even systems that are superficially similar may utilize different underlying mechanisms. This diversity is illustrated by a comparison of sex determination in three well‐studied model organisms: the fruitfly Drosophila melanogaster, the nematode Caenorhabditis elegans, and the mouse. All three animals exhibit male heterogamety, extensive sexual dimorphism and sex chromosome dosage compensation, yet the molecular and cellular processes involved are now known to be quite unrelated. The similarities (...) must have arisen by convergent evolution. Studies of sex determination demonstrate that evolution can produce a variety of solutions to the same basic problems in development. (shrink)

The molecular mechanism of temperature‐dependent sex determination (TSD) is a long‐standing mystery. How is the thermal signal sensed, captured and transduced to regulate key sex genes? Although there is compelling evidence for pathways via which cells capture the temperature signal, there is no known mechanism by which cells transduce those thermal signals to affect gene expression. Here we propose a novel hypothesis we call 3D‐TSD (the three dimensions of thermolabile sex determination). We postulate that the genome has capacity (...) to remodel in response to temperature by changing 3D chromatin conformation, perhaps via temperature‐sensitive transcriptional condensates. This could rewire enhancer–promoter interactions to alter the expression of key sex‐determining genes. This hypothesis can accommodate monogenic or multigenic thermolabile sex‐determining systems, and could be combined with upstream thermal sensing and transduction to the epigenome to commit gonadal fate. (shrink)

In Caenorhabditis elegans, sex is determined by the number of X chromosomes which, in turn, determines the expression of the X‐linked gene xol‐1. Recent work(1) has shown that xol‐1 expression is controlled by least two distinct regulatory mechanisms, one transcriptional and another post‐transcriptional. The transcriptional regulator is a repressor acting in XX embryos; although the specific gene has not been identified, the chromosome region has been defined. A previously defined regulator of xol‐1, known as fox‐1, maps to a different region (...) of the X chromosome and works post‐transcriptionally, consistent with the identification of the fox‐1 gene product as a putative RNA binding protein(2). (shrink)

Our goal in this paper is to reassess the relationship between norms and life by drawing on the philosophy of Georges Canguilhem, particularly some of his unpublished lectures about teratology and sexual determination. First, we discuss the difficulties Canguilhem identified in the introduction of life and sexuality as objects of philosophical reflection. Second, we reassess Canguilhem’s understanding of normativity as rooted in life and the axiological activity of the living. Third, we analyze how Canguilhem drew from past and contemporary (...) teratology to conceive of the notions of anomaly and abnormality. Finally, we reconstruct Canguilhem’s analysis of a case of hermaphroditism, highlighting how he presented it as evidence that sexual determination is the result of a normative choice. One of the key contributions of the paper to scholarly literature on Canguilhem is a better understanding of his notion of choice, which was considered not the conscious and intentional act of a subject but rather an axiological activity of the living. We conclude by positioning Canguilhem’s concept of normativity and his belief that norms are produced by the living in relation to the naturalist/normativist divide in medicine. (shrink)

Maize develops separate male and female flowers in different locations on a single plant. Male flowers develop at the tip of the shoot in the tassel, and female flowers develop on the ears, which terminate short branches. The development of male flowers in tassels and female flowers in ears is the result of selective abortion of pistils or stamens, respectively, in developing florets. Genetic analysis has shown that stamen abortion and pistil abortion are under the control of two different genetic (...) pathways. Local levels of the plant hormone gibberellic acid determine whether or not stamens are suppressed. Pistil abortion is under the regulation of the tassel seed genes, one of which has been shown to encode a short‐chain alcohol dehydrogenase. The tassel seed genes play a role in regulating the fate of inflorescence meristems as well as pistil primordium fate. (shrink)

The endangered species Tokudaia osimensis has the unique chromosome constitution of 2n = 25, with an XO/XO sex chromosome configuration (2n = 25; XO). There is urgency to preserve this species and to elucidate the regulator(s) that can discriminate the males and females arising from the indistinguishable sex chromosome constitution. However, it is not realistic to examine this rare animal species by sacrificing individuals. Recently, true naïve induced pluripotent stem cells were successfully generated from a female T. osimensis, and the (...) sexual plasticity of its germ cells was elucidated. This achievement constitutes the basis of an attractive research area, including embryonic fate determination, sex determination, and factor(s) that can replace the Y chromosome. In this essay, concrete strategies to conserve rare animal species and to reveal their specific characteristics using other compatible and abundant animals are proposed. -/- . (shrink)

A hypothesis on the evolutionary origin of the genetic pathway of sex determination in the nematode Caenorhabditis elegans is presented here. It is suggested that the pathway arose in steps, driven by frequency‐dependent selection for the minority sex at each step, and involving the sequential acquisition of dominant negative, neomorphic genetic switches, each one reversing the action of the previous one. A central implication is that the genetic pathway evolved in reverse order from the final step in the hierarchy (...) up to the first. The possible applicability of the model to the other well‐characterized sex determination pathway, that of Drosophila melanogaster, and to sex determination in mammals, is discussed, along with some potential implications for pathway evolution in general. Finally, the specific molecular and population genetic questions that the model raises are described and some tests are proposed. (shrink)

Sex selection in India and China is fostered by a limiting social structure that disallows women from performing the roles that men perform, and relegates women to a lower status level. Individual parents and individual families benefit concretely from having a son born into the family, while society, and girls and women as a group, are harmed by the widespread practice of sex selection. Sex selection reinforces oppression of women and girls. Sex selection is best addressed by ameliorating the situations (...) of women and girls, increasing their autonomy, and elevating their status in society. One might argue that restricting or prohibiting abortion, prohibiting sex selection, and prohibiting sex determination would eliminate sex selective abortion. But this decreases women's autonomy rather than increases it. Such practices will turn underground. Sex selective infanticide, and slower death by long term neglect, could increase. If abortion is restricted, the burden is placed on women seeking abortions to show that they have a legally acceptable or legitimate reason for a desired abortion, and this seriously limits women's autonomy. Instead of restricting abortion, banning sex selection, and sex determination, it is better to address the practice of sex selection by elevating the status of women and empowering women so that giving birth to a girl is a real and positive option, instead of a detriment to the parents and family as it is currently. But, if a ban on sex selective abortion or a ban on sex determination is indeed instituted, then wider social change promoting women's status in society should be instituted simultaneously. (shrink)

Two prevailing paradigms explain the diversity of sex-determining modes in reptiles. Many researchers, particularly those who study reptiles, consider genetic and environmental sex-determining mechanisms to be fundamentally different, and that one can be demonstrated experimentally to the exclusion of the other. Other researchers, principally those who take a broader taxonomic perspective, argue that no clear boundaries exist between them. Indeed, we argue that genetic and environmental sex determination in reptiles should be seen as a continuum of states represented by (...) species whose sex is determined primarily by genotype, species where genetic and environmental mechanisms coexist and interact in lesser or greater measure to bring about sex phenotypes, and species where sex is determined primarily by environment. To do otherwise limits the scope of investigations into the transition between the two and reduces opportunities to use studies of reptiles to advance understanding of vertebrate sex determination generally. © 2004 Wiley Periodicals, Inc. (shrink)

Sex determination in most organisms involves a simple binary fate choice between male or female development; the outcome of this decision has profound effects on organismal biology, biochemistry and behaviour. In the nematode C. elegans, there is also a binary choice, either male or hermaphrodite. In C. elegans, distinct genetic pathways control somatic and germline sexual cell fate. Both pathways share a common set of globally acting regulatory genes; however, germline-specific regulatory genes also participate in the decision to make (...) male or female gametes. The determination of sexual fate in the germline of the facultative hermaphrodite poses a special problem, because first sperm then oocytes are produced. It has emerged that additional layers of post-transcriptional regulation have been imposed to modulate the activities of the global sex-determining genes, tra-2 and fem-3; the balance between these activities is crucial in controlling sexual cell fate in the hermaphrodite germline. BioEssays 23:596–604, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The signal for sex determination in the nematode Caenorhabditis elegans is the ratio between the number of × chromosomes and the number of sets of autosomes (the X/A ratio). Animals with an X/A ratio of 0.67 (a triploid with two × chromosomes) or less are males. Animals with an X/A ratio of 0.75 or more are hermaphrodites. Thus, diploid males have one × chromosome and diploid hermaphrodites have two × chromosomes. However, the difference in X‐chromosome number between the sexes (...) is not reflected in general levels of X‐linked gene expression because of the phenomenon of dosage compensation. In dosage compensation, X‐linked gene expression appears to be ‘turned down’ in 2X animals to the 1X level of expression. An intriguing and unexplained finding is that mutations and X‐chromosome duplications that elevate X‐linked gene expression also feminize triploid males. One way that this relationship between sex determination and X‐linked gene expression may be operating is discussed. (shrink)