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Kosswig around 1964, shortly after independently segregating pairs of

Quick guide PSD was described in platyfish chromosomes. Similar scenarios
(Xiphophorus spp.). In the case of occur in sticklebacks and other fishes,
platyfish, some populations have where multiple sex chromosomes are
Polygenic sex both a Y male determination allele present, but pair in such a way as
determination and a W female determination allele
segregating at the same chromosome
to consistently segregate as if they
were a single chromosome pair. Since
pair. Despite the discovery and there do not appear to be multiple
Emily C. Moore description of PSD nearly fifty years genetic sex switch loci, and the sex
and Reade B. Roberts ago, the phenomenon remains chromosomes are not segregating
relatively unknown, and only recently independently, these cases do not
What is sex determination? Sex have we begun realizing the potential meet the requirements of the PSD
determination is the mechanism by extent of PSD systems across taxa. definition above.
which sexual organisms direct gonad
development towards distinct but What species have PSD? Polygenic In PSD, which sex determination
reproductively compatible outcomes. sex determination is known to locus ‘wins’ to determine sex?
Molecular signaling cascades in occur naturally in various species of The locus that wins and ultimately
the developing gonad provide insects, mammals, fish, and plants. determines the fate of the gonad
instructions to the tissue to develop Some housefly (Musca domestica) depends on the system being
as male or female (or in some cases populations have male and female examined (Figure 1). In platyfish,
hermaphrodite), and these signals sex determination loci on autosomes pygmy mice, and lemmings, the
can be initiated in different ways. Sex in addition to a male sex determiner ancestral state was an XY system.
can be determined by environmental on a morphologically distinct Y In these cases, one of the X
cues (such as temperature), or chromosome. Among vertebrates, chromosomes gained a female
genetically. Genetic sex determination birds and mammals generally have sex-determination allele that is
occurs when an inherited difference evolutionarily conserved monogenic dominant to the Y, directing ovary
in genes or chromosomes initiates sex determination systems; however, development in WY (also referred to
the sex determination signal, acting African pygmy mice (Mus minutoides), as X*Y) individuals. Some species
as a ‘master switch’ for male or some species of South American field of cichlid fish from Lake Malawi
female development. Perhaps the mice (Akodon spp.) and two species have an XY locus and a WZ locus
most widely known genetic sex of lemmings (Myopus schisticolor on distinct chromosome pairs,
determination system is the male and Dicrostonyx torquatus) have and when these occur in the same
heterogametic XX/XY system found in independently evolved an additional, individual, the W female determiner
most mammals, where the Sry gene independently assorting female sex wins, and the individual develops as
on the Y chromosome determines determination locus. Fish have been female. The end result of PSD is not
male sex. Thus, XY individuals the most well studied vertebrate always skewed towards females; in
develop as males, and XX individuals lineage with regard to variety of some housefly populations, a sex
develop as females. Many other sex determination mechanisms, determination locus on an autosome
organisms, including birds, have a and it is within this group that PSD causes XX flies to develop as male.
ZZ/ZW chromosomal system, where was initially discovered. Additional In other cases, including zebrafish
heterogametic ZW individuals develop examples of PSD have recently been and cichlids, sex determination
as female, and homogametic ZZ found in fish, including in African likely results from a combination of
individuals develop as male (Figure 1). cichlid fish (Metriaclima spp.) and additive and epistatic effects at many
the developmental model zebrafish loci. Thus, an allele that wins in one
How is polygenic sex determination (Danio rerio). Outside of the animal combination of sex determination
different? In the XY and ZW systems kingdom, some gynodioecious loci genotypes may lose in another.
described above, a single genetic plants (such as Thymus vulgaris Indeed, in some gynodioecious plants,
locus, often on a morphologically and Plantago coronopus) appear to the outcome of a genetic contest
distinct chromosome, acts as the determine hermaphroditic versus between ‘anti-male’ mitochondrial
master switch for sex determination. female sex through interactions of loci and nuclear ‘pro-male’ restorer
In polygenic sex determination multiple cytoplasmic and nuclear loci. loci ultimately determines female
(PSD), multiple, independently versus hermaphrodite development.
segregating sex ‘switch’ loci or Do all species with multiple sex Truly, there is striking diversity in the
alleles determine sex within a chromosomes have PSD? Not different ways PSD has independently
species. Polygenic systems can arise necessarily. For example, the platypus evolved across these taxa.
through modifications of existing (Orinthorhynchus anatinus) has five
sex chromosomes that create a third sex chromosome pairs — males Why haven’t I heard of PSD
functional sex chromosome at the have five X and five Y chromosomes. before? Simply put, historical
same locus, or through modifications However, these chromosomes form and technical bias. Genetic sex
of autosomal loci elsewhere in the chains and segregate together during determination was first identified in
genome that create new inputs for meiosis, so that they effectively insects, where it was found in the
regulation of gonad development. The behave as a single X and a single form simplest to detect and easiest
term ‘polygenic sex determination’ Y chromosome when distributed to understand: a single, highly
appears to have been coined by to gametes, rather than five differentiated sex chromosome was
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A B C D
Male heterogametic Female heterogametic Single-locus polygenic Multi-locus polygenic

P XY XX ZZ ZW XY XW ZZ XY ZW XX

F1 XY XX ZZ ZW XY XW XX WY ZZ XY ZZ XX ZW XX ZW XY

Current Biology

Figure 1. Inheritance patterns in male heterogametic, female heterogametic, and polygenic sex determination systems.
(A) The male heterogametic XX/XY system represented in humans, where a degenerated Y chromosome inherited from the father determines
male sex in offspring. (B) The female heterogametic ZZ/ZW system represented in Northern cardinal (Cardinalis cardinalis), where a degenerated
W chromosome inherited from the mother determines female sex in offspring. (C) African pygmy mice (Mus minutoides) represent a single-locus
XYW system, where the inheritance of a Y by itself determines male development, but this effect is overridden by the presence of a novel W
female sex determiner (also referred to as X*). The system produces one genotypic male class, and three genotypic female classes. (D) African
cichlid fish (Metriaclima pyrsonotus) represent a multi-locus system, where alleles at an XY locus on chromosome 7 (green) and a ZW locus on
chromosome 5 (yellow) segregate independently. The W allele overrides the Y male determiner such that ZW, XY individuals are female, again
resulting in one genotypic male class, and three genotypic female classes. Additionally, a pigmentation allele tightly linked to the W locus pro-
duces a color polymorphism in female offspring. Note that in both polygenic systems other types of crosses with different outcomes are pos-
sible, since there are multiple genetic types of females.

found in one sex but not the other. PSD systems may have remained families or populations. For example,
This precedent was confirmed in largely undiscovered, or, when when mapping sex determination
mammals, birds, and important they were identified, dismissed as in some African cichlids, PSD could
model systems like Drosophila odd exceptions to the rule. Early be missed by chance sampling of
melanogaster. Later, additional studies of sex ratios in some species families whose parents carry only
types of chromosome-level sex suggested PSD, but until relatively one sex determiner (e.g., a cross
determination were identified, recently, the technology was not between a ZZ/XY male and a ZZ/XX
including XO systems (found in the available to readily identify multiple, female would allow mapping of the
nematode Caenorhabditis elegans) interacting sex determination loci XY locus, but not the ZW locus).
and haploid–diploid systems in many species. With the advent of Ultimately, discovery of PSD systems
(found in Hymenopteran insects, less expensive genome sequencing, requires truly representative mapping
including ants and bees). The ease and more sophisticated strategies strategies as well as openness
of studying chromosomal sex, where for genetic mapping, we expect to the possibility that multiple
sex chromosomes could be readily that instances of PSD will become sex determination loci may be
identified under a microscope, easier to find, and the catalog of segregating in a population.
surely biased the study of sex examples will grow. In fact, some
determination against autosomal species traditionally thought to have Why does PSD exist? One hypothesis
sex determination loci systems for a monogenic sex determination to explain the evolution of PSD is
the greater part of the last century. system may demonstrably have PSD that a novel sex determination locus
Since this historical bias had a upon further study, including those will be maintained if it provides a
large conceptual impact on the species for which sex determination benefit to individuals carrying it.
study of biology from evolutionary has not been examined or has only For example, in both houseflies and
theory to developmental research, been examined in a small number of South American field mice, individuals
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with the more recently evolved sex represents an evolutionarily stable gene networks and epistasis, and
determination alleles have higher strategy in some scenarios. The allow us to ask questions about the
reproductive fitness. It is unclear alternative would require that the developmental regulation of genes
whether the gene that acts as the examples cataloged thus far all that are traditionally thought of
overriding primary sex switch has represent temporary destabilization as members of core sex signaling
pleiotropic effects modulating fitness, of a fundamental fitness trait in networks. Species with PSD also
or if the novel sex determination species, or evolutionary transitions provide snapshots of possible
locus is linked to another gene that between sex determination systems. transitions from one mode of sex
provides enhanced fitness. Novel One hypothesis for the stability of determination to another, providing
sex determination loci may also arise PSD is that it could readily produce insight into the evolution of sex
and be maintained if they resolve a multiple phenotypic or reproductive determination. Identification of
sexual conflict involving an allele that classes within a sex, or more than additional sex determination genes
provides an adaptive benefit to one two sex types. If these class or type and interactions should also provide
sex to the detriment of the other. Such differences result in alternative fitness insight into sexual development and
a scenario appears in African cichlid benefits, selection may maintain disease. Ultimately, studying intrasex
fish, where a pigmentation allele them in the population, contributing differences in PSD models may
provides camouflage to females, to PSD being an evolutionarily stable provide insight into the continuum
but disrupts sexually selected male scenario. of sex differences in humans, and
nuptial color and thus reduces male challenge long held notions of the
mating success. The pigmentation How many sexes are there? The evolution and development of sex and
allele is tightly linked to a recently traditional view of primary, gonadal sexual dimorphism.
evolved female sex determination sex is of a binary trait — each
locus, ensuring that the color trait individual is either male or female. Where can I find out more?
will only be expressed in females, the With multiple interacting loci Anderson, J.L., Rodríguez Marí, A., Braasch,
I., Amores, A., Hohenlohe, P., Batzel, P.,
benefiting sex. Similar sexual conflicts determining primary sex, there are as and Postlethwait, J.H. (2012). Multiple
could be evolutionarily intertwined many genetic sexes for a given group sex-associated regions and a putative sex
chromosome in zebrafish revealed by RAD
with each sex determination locus in as there are possible combinations mapping and population genomics. PLoS One
PSD systems. of sex determination loci. In known 7, e40701.
cases of PSD in animals, primary sex Charlesworth, D., and Mank, J.E. (2010). The
birds and the bees and the flowers and the
Is PSD evolutionarily stable? The remains binary, but evidence suggests trees: lessons from genetic mapping of sex
answer is not entirely clear. One that genotypically different individuals determination in plants and animals. Genetics
186, 9–31.
argument against stable PSD is that of the same primary sex can have Ehlers, B.K., Maurice, S., and Bataillon, T. (2005).
one sex determination allele would differential reproductive success, Sex inheritance in gynodioecious species: a
provide a reproductive fitness benefit as mentioned above. Thus, even polygenic view. Proc Biol Sci. 272, 1795–1802.
Ezaz, T., Stiglec, R., Veyrunes, F., and Marshall
over another, and selection would though primary sex may be binary Graves, J.A. (2006). Relationships between
fix it as the sole sex determiner. in these cases, PSD may produce vertebrate ZW and XY sex chromosome
systems. Curr. Biol. 16, R736–R743.
Another concern is that PSD could different classes within a single sex, Kosswig, C. (1964). Polygenic sex determination.
produce highly skewed sex ratios, or individuals of the same primary Experientia 20, 190–199.
depending on the number of loci sex with strikingly different secondary Kozielska, M., Pen, I., Beukeboom, L.W., and
Weissing, F.J. (2006). Sex ratio selection
and how they interact. However, sexual characteristics. In some and multi-factorial sex determination in the
depending on how different sex plants, PSD systems may produce housefly: a dynamic model. J. Evol. Biol. 19,
879–888.
switches are integrated during sexual what could be considered more Liew, W.C., Bartfai, R., Lim, Z., Sreenivasan, R.,
development, and the frequencies than two sexes. For example, in the Siegfried, K.R., and Orban, L. (2012). Polygenic
of sex determination alleles in domesticated cantaloupe, Cucumis sex determination system in zebrafish. PLoS
One. 7, e34397.
populations, these arguments may melo, multiple loci interact to produce Ming, R., Bendahmane, A., and Renner, S.S.
not be valid in all circumstances. In four sexes, with andromonoecious, (2011). Sex chromosomes in land plants. Annu.
Rev. Plant Biol. 62, 485–514.
a simple sense, PSD systems may monoecious, gynoecious, and Rens, W., Grützner, F., O’Brien, P.C., Fairclough,
be inherently unstable if they can hermaphrodite individuals in some H., Graves, J.A., and Ferguson-Smith,
easily revert to single factor systems cultivars (though it is not clear if M.A. (2004). Resolution and evolution of
the duck-billed platypus karyotype with
by loss of sex determination loci via such a system occurs naturally). In an X1Y1X2Y2X3Y3X4Y4X5Y5 male sex
drift or selection. In some species light of the variability in the genetic chromosome constitution. Proc. Natl. Acad.
Sci. USA 101, 16257–16261.
with PSD (such as houseflies and controls of sex determination and Ser, J.R., Roberts, R.B., and Kocher, T.D.
cichlids), sex determination occurs development, it may be beneficial (2010). Multiple interacting loci control sex
normally if only a single genetic factor to re-evaluate our view of sex as a determination in Lake Malawi cichlid fish.
Evolution 64, 486–501.
is present, and different populations binary trait. Veyrunes, F., Chevret, P., Catalan, J., Castiglia,
appear to have monogenic versus R., Watson, J., Dobigny, G., Robinson, T.J.,
and Britton-Davidian, J. (2010). A novel sex
polygenic sex determination. Thus, Why study PSD? Organisms with PSD determination system in a close relative of the
it appears that only a single genetic provide us with models of multiple house mouse. Proc Biol Sci. 277, 1049–1056.
switch is required for proper sexual genetic switches that interact in Volff, J.N., and Schartl, M. (2001). Variability of
genetic sex determination in poeciliid fishes.
reproduction in these species, even different combinations to produce Genetica 111, 101–110.
though multiple sex determination loci a fundamental fitness phenotype
can be present. However, we suggest and resounding effects throughout Department of Genetics, North Carolina
that the widespread presence of an organism. These models can State University, Raleigh, NC 27695, USA.
PSD across taxa suggests that it be used to study the evolution of E-mail: [email protected]