Molecular Evolution of Genes Involved in Vertebrate Sex Determination


Four sex‐determining genes (SDGs) had been reported in vertebrates until 2011: Y‐linked Sry in eutherian mammals, Z‐linked Dmrt1 in the chicken, W‐linked Dm‐W in the African clawed frog Xenopus laevis and Y‐linked Dmy (also called as dmrt1bY) in the teleost fish medaka. These genes encode deoxyribonucleic acid (DNA)‐binding proteins. Both Dm‐W and Dmy emerged through duplication of Dmrt1, whereas Sry evolved from allelic Sox3. Interestingly, in 2012, four different types of SDGs, which might not encode DNA‐binding proteins, were reported in teleost fish: Patagonian pejerrey amhy, Oryzias luzonensisGsdfY, Takifugu rubripesAmhr2, and rainbow trout sdY. Although these SDGs are all sex chromosome‐linked, a variety of them may be involved in the evolution of sex chromosomes. A coevolution model of SDGs and sex chromosomes has been proposed: undifferentiated or specialised sex chromosomes could allow diversity of SDGs or tend to fix a certain SDG, respectively, during species diversity in vertebrates.

Key Concepts:

  • There are a variety of SDGs including transcription factor genes and TGF‐β signal‐related genes.

  • SDGs could be classified into two types: insertion and mutations after duplication, and mutations of an allelic gene.

  • SDGs Dmy/Dm‐W and Sry, which evolved through duplication of Dmrt1 and an allelic mutation of Sox3, respectively, have a higher substitution rate than their prototype genes.

  • Cis‐regulatory elements in most of the SDGs should have evolved for their mRNA expressions at a sex‐determining stage, but only an amino acid change by SNP between Amhr2 alleles could determine the sex in fugu fish.

  • SDGs and sex chromosomes would have coevolved during vertebrate evolution: undifferentiated or specialised sex chromosomes could allow diversity of SDGs or tend to fix a certain sex‐determining gene, respectively.

Keywords: sex; sex determination; sex chromosome; coevolution; neofunctionalisation; Dmrt1; Sry; TGF‐β; duplication; molecular evolution

Figure 1.

Various SDGs and their prototype genes during vertebrate evolution. No SDGs have been identified in species having temperature sex determination. All of the SDGs are sex chromosome‐linked. Y‐linked and Z‐linked genes for testis formation are shown in blue. A W‐linked gene Dm‐W is shown in red.

Figure 2.

SDGs and sex chromosomes in Oryzias species. The data of sex chromosome are derived from Tanaka et al. . Timing of emergence/degeneration of Dmy or GsdfY is represented by arrows (Kondo et al., ; Myosho et al., ).

Figure 3.

A W‐linked sex‐determining gene Dm‐W in clawed frogs. Plus or minus shows confirmation or no confirmation of Dm‐W orthologues (Bewick et al., ). 2x, 4x, 8x and 12x indicate diploid, tetraploid, octoploid and dodecaploid.

Figure 4.

A sex‐determining gene (SDG), sex chromosome, and SD system in Takifugu and Tetraodon species. An SNP in Amhr2 is the only polymorphism associated with phenotypic sex. This SNP causes an amino acid change (H/D384). Y‐linked Amhr2 (D384) is located on chromosome 19 in three species of the genus Takifugu. The SNP is not found in Tetraodon nigroviridis (Kamiya et al., ).

Figure 5.

Coevolution model between SDGs and sex chromosomes in vertebrates. A candidate SDG emerged from a certain sex‐related gene on one chromosome of a pair of autosomes (upper middle). The candidates could be mainly clarified into two types: insertion and mutations of a duplicate, and mutations of an allelic gene. Then, the candidate gene was established as an SDG during species diversity with few morphological changes of the two chromosomes (lower left). If a new SDG candidate emerged as a stronger regulator for sex determination, the established SDG might have been degenerated into a psuedogene (lower right). The case might correspond to the sex determination in O. luzonensis (Myosho et al., ). In contrast, specialised sex differentiation might lead to stabilisation of the SDG (upper left), which probably corresponds to the case of the XY chromosomes and Sry in eutherian mammals. Therefore, it is likely that undifferentiated state of sex chromosome state in many species of fishes, amphibians and reptiles allows an SDG to change, whereas specialisation of sex chromosomes in most species of mammalians, birds and snakes could cause stabilisation of SDGs (Mawaribuchi et al., ).



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Further Reading

Eggers S and Sinclair A (2012) Mammalian sex determination – insights from humans and mice. Chromosome Research 20(1): 215–238.

Graves JA (2012) How to evolve new vertebrate sex determining genes. Developmental Dynamics 242(4): 354–359.

Kikuchi K and Hamaguchi S (2103) Novel sex‐determining genes in fish and sex chromosome evolution. Developmental Dynamics 242(4): 339–353.

O'Meally D, Ezaz T, Georges A et al. (2012) Are some chromosomes particularly good at sex? Insights from amniotes. Chromosome Research 20(1): 7–19.

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Ito, Michihiko, and Mawaribuchi, Shuuji(Sep 2013) Molecular Evolution of Genes Involved in Vertebrate Sex Determination. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0024948]