Blurring the edges in vertebrate sex determination
Introduction
Across vertebrates, primary sex determination is defined as the decision within the bipotential gonad to develop as a testis or an ovary. Within the past decade, the traditional view of this process, in which a strict division is drawn between species that employ genetic mechanisms (genetic sex determination, GSD; e.g. mammals and birds) to determine sex and those that use environmental mechanisms (such as temperature-dependent sex determination, TSD; e.g. crocodiles), has been supplanted by the theory that GSD and TSD actually represent points on a continuum along which populations can and do shift, under selective pressure [1, 2, 3••]. This novel perspective is strengthened by the recent accumulation of empirical data suggesting that genetic elements influence systems that use TSD, and that functional or vestigial temperature sensitivity is present in organisms that employ GSD, even some with heteromorphic sex chromosomes [4•, 5•, 6•, 7••]. Additionally, many of the cellular processes, transcription factors, and signaling pathways involved in sex determination and gonadogenesis are conserved across vertebrates, implying that the underlying machinery may be similar despite modifications in the dominant upstream signal used. This perspective will be discussed in the present review, in the context of converging ideas about how sex-specific development of the gonads is initiated.
Section snippets
Rapid evolutionary transitions between sex-determining mechanisms
The methods of sex determination (e.g. GSD (XX/XY, ZZ/ZW, or homomorphy), TSD, polygenic, or density-dependent) used by many species of reptile, amphibian, and fish have been elucidated in recent years (Figure 1) [3••, 8, 9, 10]. When these are plotted onto a phylogenetic map, the evolutionary lability of sex determination is apparent within several major branches of the tree, where numerous transitions must have occurred to achieve the present diversity [3••]. Most of these inferred
Overriding GSD by hormones and temperature
Eutherian mammals, with XX/XY male heterogamety, comprise one of the most strictly GSD groups in the animal kingdom. Classic work in the mouse and human systems demonstrated that expression of the Y-chromosome-linked Sry gene in the supporting cell lineage leads to their differentiation as Sertoli cells and the adoption of the testis fate [16, 17]. In the absence of this upstream signal, ovarian development ensues. The evolution of both viviparity and endothermy in eutherian mammals required a
Thermosensitive gene expression in a GSD turtle
In TSD species, many genes known to be involved in sex determination or gonadogenesis show temperature-specific expression patterns during the temperature-sensitive period of development, before sex has been determined; however, the functional significance of these findings is not clear (e.g. [33, 34, 35•, 36, 37, 38]). For example, expression of DMRT1 in the red-eared slider turtle, Trachemys scripta, is elevated at the male-producing temperature as compared to the higher female-producing
Geographic pressures on TSD
The pivotal temperature (TP) for a TSD species is defined as the range of incubation temperatures that produce a 1:1 male to female sex ratio. In many species, temperatures below the TP will yield an increasingly male-biased ratio, and higher temperatures will generate more females (MF), though this pattern is often reversed (FM). While only one TP has been observed in many species, others exhibit a FMF pattern with two distinct transition points [7••]. It has been proposed that the existence
Evolutionary advantage of TSD
As TSD has been documented in a wide array of species, it must carry selective advantages in particular environments. Unfortunately, the longevity and delayed sexual maturity characteristic of most reptilian TSD species have made direct evaluations of reproductive fitness impractical. The Charnov–Bull model predicts that TSD should be favored if the fitness of (either or both) males and females is enhanced by development under a particular set of environmental conditions [40]. In their study of
Antagonistic pathways: a plastic system for evolutionary adaptation
The decision to develop as a male or female depends on whether the gonad develops as a testis or an ovary. In mammals, this decision rests on the fate of the supporting cell lineage, which either initiates differentiation as Sertoli (male) or follicle (female) cells. Fgf9 and Wnt4 act as mutually antagonistic signals that converge on Sox9 during sex determination to regulate the fate of the supporting cell lineage in mice [42•]. Both Fgf9 and Wnt4 are expressed in the bipotential gonad. Sry
Conclusions
In contrast to the high conservation of most developmental pathways across species from Drosophila to man, a stunning variety of mechanisms of sex determination exist within the animal kingdom. The distinction between genetically and environmentally based primary signals is beginning to blur as a result of the discovery of coincident thermal and genetic influences within single species, as well as the high degree of conservation in the genes governing gonadogenesis. The model of antagonistic
Conflict of interest
The authors declare no conflict of interest.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
We thank Steve Munger and Leo DiNapoli for insightful comments and critical reading of the manuscript. Funding in the Capel laboratory is provided by the National Science Foundation (0317234) and the National Institutes of Health (HL63054 and HD39963).
References (56)
Sex determination in the teleost medaka, Oryzias latipes
Annu Rev Genet
(2005)- et al.
Sex determination. Viviparous lizard selects sex of embryos
Nature
(2001) - et al.
Developmental expression of steroidogenic factor 1 in a turtle with temperature-dependent sex determination
Gen Comp Endocrinol
(1999) - et al.
When is sex environmentally determined?
Nature
(1977) - et al.
The adaptive significance of temperature-dependent sex determination in a reptile
Nature
(2008) - et al.
Stabilization of beta-catenin in XY gonads causes male-to-female sex-reversal
Hum Mol Genet
(2008) - et al.
AMH induces mesonephric cell migration in XX gonads
Mol Cell Endocrinol
(2003) - et al.
The ends of a continuum: genetic and temperature-dependent sex determination in reptiles
Bioessays
(2004) Sex determination: are two mechanisms better than one?
J Biosci
(2008)- et al.
Exploring the evolution of environmental sex determination, especially in reptiles
J Evol Biol
(2006)
Temperature sex reversal implies sex gene dosage in a reptile
Science
Genetic evidence for co-occurrence of chromosomal and thermal sex-determining systems in a lizard
Biol Lett
Relic thermosensitive gene expression in a turtle with genotypic sex determination
Evol Int J Org Evol
Geographic variation in the pattern of temperature-dependent sex determination in the American snapping turtle (Chelydra serpentina)
J Zool
Evidence for heteromorphic sex chromosomes in males of Rana tagoi and Rana sakuraii in Nishitama district of Tokyo (Anura: Ranidae)
Chromosome Res
Environment and sex determination in farmed fish
Comp Biochem Physiol C Toxicol Pharmacol
Change of the heterogametic sex from male to female in the frog
Genetics
The ZZ/ZW sex-determining mechanism originated twice and independently during evolution of the frog, Rana rugosa
Heredity
DMY is a Y-specific DM-domain gene required for male development in the medaka fish
Nature
Oryzias curvinotus has DMY, a gene that is required for male development in the medaka, O. latipes
Zool Sci
Absence of the candidate male sex-determining gene dmrt1b(Y) of medaka from other fish species
Curr Biol
A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes
Nature
The molecular genetics of Sry and its role in mammalian sex determination
Philos Trans R Soc Lond B Biol Sci
The behavior of the X- and Y-chromosomes in the oocyte during meiotic prophase in the B6.Y(TIR)sex-reversed mouse ovary
Reproduction
Functional coherence of the human Y chromosome
Science
Maternal basking behaviour determines offspring sex in a viviparous reptile
Proc Biol Sci
Evolution of sex determination and the Y chromosome: SRY-related sequences in marsupials
Nature
Sex chromosomes and reproductive anatomy of some intersexual marsupials
J Reprod Fert
Cited by (70)
Morphological and transcriptional analysis of sexual differentiation and gonadal development in a burrowing fish, the four-eyed sleeper (Bostrychus sinensis)
2023, Comparative Biochemistry and Physiology - Part D: Genomics and ProteomicsMolecular characterization of vasa homologue in marbled goby, Oxyeleotris marmorata: Transcription and localization analysis during gametogenesis and embryogenesis
2019, Comparative Biochemistry and Physiology Part - B: Biochemistry and Molecular BiologyCitation Excerpt :Gametogenesis starts at the specification of primordial germ cells (PGCs), which segregate from the early embryonic cells, migrate towards genital ridge, and become gonia, oogonia in ovary or spermatogonia in testis in fish (Strome and Updike, 2015). Under the regulation of intrinsic gene expression (such as SRY, DMRT1) (Wallis et al., 2008; Zarkower, 2013) or extrinsic factors induction (such as hormones and temperature) (Barske and Capel, 2008), gonia undergo differentiation, meiosis entry and progression, culminating in the production of haploid gametes, eggs and sperms (Ungewitter and Yao, 2013). Germ cells show some intrinsic histological characteristics that are different from those of somatic cells, such as large round nucleus, single large nucleolus, and germ plasm (Extavour and Akam, 2003), a structure also referred to as nuage (polar granules) involving in germ cell formation in animals such as worm, fruitfly and fish (Xu et al., 2010).
Natural sex change in fish
2019, Current Topics in Developmental BiologyCitation Excerpt :This diversity in mechanism is startling when one considers the critical importance of sex determination for sexual reproduction and species persistence (Capel, 2017). However, despite the obvious diversity of sex-determining mechanisms, sexual fate was for many years considered to be fixed following downstream sexual differentiation cascades, which rely heavily on a few transcription factors and steroid hormones that are evolutionarily conserved (Barske & Capel, 2008; Guiguen, Fostier, Piferrer, & Chang, 2010; Herpin & Schartl, 2011a, 2011b; Kobayashi, Nagahama, & Nakamura, 2013; Matson & Zarkower, 2012; Piferrer & Guiguen, 2008). However, we increasingly recognize that gonadal sexual fate is not only established by competition for primacy between two sexes via antagonistic signaling pathways during embryonic development (Ungewitter & Yao, 2013; Windley & Wilhelm, 2015), but that it requires active maintenance to suppress the opposite sex during adulthood (Lindeman et al., 2015; Matson et al., 2011; Uhlenhaut et al., 2009).
Expression of sf1 and dax-1 are regulated by thyroid hormones and androgens during Silurana tropicalis early development
2018, General and Comparative EndocrinologySex determination and gonadal development in birds
2018, Encyclopedia of Reproduction