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Biomolecules
Special Issues
Molecular Insights into Sex and Evolution
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Molecular Insights into Sex and Evolution

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Genetics".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 10629

Special Issue Editors

Prof. Dr. Ikuo Miura

E-Mail Website
Guest Editor
Amphibian Research Center, Hiroshima University, Higashi-Hiroshima 739-8526, Japan
Interests: genetics: sex chromosome evolution and speciation
Dr. Michihiko Ito

E-Mail Website
Guest Editor
Department of Biosciences, School of Science, Kitasato University, Sagamihara 252-0373, Japan
Interests: evolutionary biology: sex determination and genome evolution

Special Issue Information

Dear Colleagues,

Sexual reproduction is a unique invention of the evolution of eukaryote life, different to that of prokaryotes. This sexual reproduction system has largely contributed to the production of eukaryote biodiversity by means of combining and shuffling genomes among different individuals, and this process continues to see itself diversified during evolution. Therefore, sex and evolution in eukaryotes are tightly linked to each other. Nevertheless, the sexual reproduction system remains a significant issue that warrants uncovering on the molecular level, specifically concerning genetic mechanisms. Therefore, we have launched a Special Issue entitled “Molecular Insights into Sex and evolution”, and we are pleased to invite you to submit your manuscripts. Research areas may include (but are not limited to) sex determination, sex chromosome evolution, reproduction, hybridization, speciation, and phylogenetic evolution. In this Special Issue, original research articles and reviews are welcome. Moreover, our aim is to unveil the genetic mechanisms of sex and evolution and understand the evolutionary reasons as to why sexual systems are as malleable and diverse as they are. 

We look forward to receiving your contributions.

Prof. Dr. Ikuo Miura
Dr. Michihiko Ito
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • sex determination
  • sex chromosome evolution
  • reproduction
  • hybridization
  • speciation
  • evolution
  • animals
  • vertebrates

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Published Papers (5 papers)

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Research

26 pages, 3890 KB  
Article
Gene Duplication, Translocation, and Molecular Evolution of Dmrt1 and Related Sex-Determining Genes in Anurans
by Sagar S. Shinde, Paris Veltsos and Wen-Juan Ma
Biomolecules 2025, 15(9), 1306; https://doi.org/10.3390/biom15091306 - 11 Sep 2025
Viewed by 182
Abstract
Sex determination, the developmental process that directs embryos toward male or female fates, is controlled by master sex-determining genes whose origins and evolutionary dynamics remain poorly understood outside of a few model systems. In contrast to the highly differentiated sex chromosomes of mammals, [...] Read more.
Sex determination, the developmental process that directs embryos toward male or female fates, is controlled by master sex-determining genes whose origins and evolutionary dynamics remain poorly understood outside of a few model systems. In contrast to the highly differentiated sex chromosomes of mammals, birds, and Drosophila, most anurans (frogs and toads) maintain homomorphic sex chromosomes that exhibit a rapid turnover, even among closely related species. Master sex-determining genes evolve via gene duplication or via allelic diversification, and sex chromosome turnover is driven by gene translocation or novel mutations in the existing genes involved in the sexual developmental pathway. To uncover the mechanisms underlying the emergence of master sex-determining genes and sex chromosome turnover, we analyzed 53 published anuran genomes and one caecilian genome (>200 Mya divergence) and available transcriptomes. We asked how often master sex-determining genes arise by gene duplication, whether and how often gene translocation associates with sex chromosome turnover, and if master sex-determining genes evolve under positive selection. We find that chromosome-level synteny is remarkably conserved, with only a few fusions or fissions and no evidence for translocation of four candidate master sex-determining genes (Dmrt1, Foxl2, Bod1l, and Sox3). Only Dmrt1 duplicated in 3 out of 50 species (excluding tetraploid Xenopus), and it showed strong testis-biased expression in all 8 species with available gonadal expression data. While Dmrt1 has evolved under purifying selection, Dmrt1 duplicates exhibit elevated nonsynonymous substitution rates and tendency towards positive selection. Lineage-specific amino acid changes were observed in the conserved DM domain of Dmrt1. These results demonstrate that, in anurans, master sex-determining genes rarely arise via gene duplication, and more likely evolve via allelic diversification. Sex chromosome turnover is not associated with gene translocation and is more likely driven by mutations on genes involved in sexual developmental pathways. All candidate sex-determining genes were under strong purifying selection, with the exception of duplications which are linked to positive selection. Our results suggest future research on anuran sex determination and sex chromosome evolution should focus on identifying allelic diversification and novel mutations on genes involved in sexual developmental pathways. Full article
(This article belongs to the Special Issue Molecular Insights into Sex and Evolution)
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13 pages, 2448 KB  
Article
Differentiation of Dmrt1 Z and W Homologs Occurred Independently in Two Gekko hokouensis Populations
by Momoka Senga, Nao Kaneko, Yoichi Matsuda and Kazumi Matsubara
Biomolecules 2025, 15(9), 1293; https://doi.org/10.3390/biom15091293 - 8 Sep 2025
Viewed by 350
Abstract
Gekko hokouensis is a gecko species widely distributed across East Asia. Although most of the Japanese populations possess ZW sex chromosomes (female heterogamety), the degree of sex chromosome differentiation varies among populations. The gene encoding for Dmrt1, a transcription factor involved in testis [...] Read more.
Gekko hokouensis is a gecko species widely distributed across East Asia. Although most of the Japanese populations possess ZW sex chromosomes (female heterogamety), the degree of sex chromosome differentiation varies among populations. The gene encoding for Dmrt1, a transcription factor involved in testis development in vertebrates, is located on the Z and W sex chromosomes of this species and is therefore a candidate of the sex-determining gene. In this study, we investigated the gene structure of the Z and W homologs of Dmrt1 in two populations of Gekko hokouensis from the Ishigaki Island and Okinawa Island. In the Ishigaki population, the ZW chromosome pair is morphologically undifferentiated, whereas in the Okinawa population the ZW pair is heteromorphic. In the Okinawa population, promoter and exon sequences were nearly identical between the Z and W homologs, and no non-synonymous substitution was detected. In contrast, the W homolog in the Ishigaki population exhibited 42 bp and 12 bp deletions in exon 2. The predicted three-dimensional protein structure revealed a rearrangement of the C-terminal region in the W homolog that may interfere with target site binding. These results indicate that differentiation between Z and W homologs of Dmrt1 has occurred independently in each population. Our findings highlight the diversity of sex chromosome evolution and sex-determining mechanisms even within a single species. Full article
(This article belongs to the Special Issue Molecular Insights into Sex and Evolution)
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25 pages, 1271 KB  
Article
New Insights into the Sex Chromosome Evolution of the Common Barker Frog Species Complex (Anura, Leptodactylidae) Inferred from Its Satellite DNA Content
by Lucas H. B. Souza, Juan M. Ferro, Helena M. Milanez, Célio F. B. Haddad and Luciana B. Lourenço
Biomolecules 2025, 15(6), 876; https://doi.org/10.3390/biom15060876 - 16 Jun 2025
Viewed by 770
Abstract
Satellite DNAs (satDNAs) play a crucial role in understanding chromosomal evolution and the differentiation of sex chromosomes across diverse taxa, particularly when high karyotypic diversity occurs. The Physalaemus cuvieri–Physalaemus ephippifer species complex comprises at least seven divergent lineages, each exhibiting specific karyotypic signatures. [...] Read more.
Satellite DNAs (satDNAs) play a crucial role in understanding chromosomal evolution and the differentiation of sex chromosomes across diverse taxa, particularly when high karyotypic diversity occurs. The Physalaemus cuvieri–Physalaemus ephippifer species complex comprises at least seven divergent lineages, each exhibiting specific karyotypic signatures. The group composed of Ph. ephippifer, Lineage 1B of ‘Ph. cuvieri’ (L1B), and a lineage resulting from their secondary contact is especially intriguing due to varying degrees of sex chromosome heteromorphism. In this study, we characterized the satellitome of Ph. ephippifer in order to identify novel satDNAs that may provide insights into chromosomal evolution, particularly concerning sex chromosomes. We identified 62 satDNAs in Ph. ephippifer, collectively accounting for approximately 10% of the genome. Notably, nine satDNA families were shared with species from distantly related clades, raising questions about their potential roles in anurans genomes. Among the seven satDNAs mapped via fluorescent in situ hybridization, PepSat3 emerged as a strong candidate for the centromeric sequence in this group. Additionally, PepSat11 and PepSat24 provided evidence supporting a translocation involving both arms of the W chromosome in Ph. ephippifer. Furthermore, a syntenic block composed of PepSat3, PcP190, and PepSat11 suggested an inversion event during the divergence of Ph. ephippifer and L1B. The variation in signal patterns of satDNAs associated with nucleolar organizer regions (NORs) highlights the complexity of NOR evolution in this species complex, which exhibits substantial diversity in this genomic region. Additionally, our findings for PepSat30-350 emphasize the importance of validating the sex-biased abundance of satDNAs. Full article
(This article belongs to the Special Issue Molecular Insights into Sex and Evolution)
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29 pages, 4533 KB  
Article
Insights into Solea senegalensis Reproduction Through Gonadal Tissue Methylation Analysis and Transcriptomic Integration
by Daniel Ramírez, Marco Anaya-Romero, María Esther Rodríguez, Alberto Arias-Pérez, Robert Mukiibi, Helena D’Cotta, Diego Robledo and Laureana Rebordinos
Biomolecules 2025, 15(1), 54; https://doi.org/10.3390/biom15010054 - 2 Jan 2025
Viewed by 1363
Abstract
Fish exhibit diverse mechanisms of sex differentiation and determination, shaped by both external and internal influences, often regulated by distinct DNA methylation patterns responding to environmental changes. In S. senegalensis aquaculture, reproductive issues in captivity pose significant challenges, particularly the lack of fertilization [...] Read more.
Fish exhibit diverse mechanisms of sex differentiation and determination, shaped by both external and internal influences, often regulated by distinct DNA methylation patterns responding to environmental changes. In S. senegalensis aquaculture, reproductive issues in captivity pose significant challenges, particularly the lack of fertilization capabilities in captive-bred males, hindering genetic improvement measures. This study analyzed the methylation patterns and transcriptomic profiles in gonadal tissue DNA from groups differing in rearing conditions and sexual maturity stages. RRBS (Reduced Representation Bisulfite Sequencing) was employed to detect notable methylation variations across groups, while RNA was extracted and sequenced for differential expression analysis. Our findings suggest that DNA methylation significantly regulates gene expression, acting as a mechanism that can both repress and enhance gene expression depending on the genomic context. The complexity of this epigenetic mechanism is evident from the varying levels of methylation and correlation rates observed in different CpGs neighboring specific genes linked to reproduction. Differential methylation comparisons revealed the highest number of differently methylated CpGs between maturation stages, followed by rearing conditions, and lastly between sexes. These findings underscore the crucial role of methylation in regulating gene expression and its potential role in sex differentiation, highlighting the complex interplay between epigenetic modifications and gene expression. Full article
(This article belongs to the Special Issue Molecular Insights into Sex and Evolution)
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16 pages, 7244 KB  
Article
Disruption of Sex-Linked Sox3 Causes ZW Female-to-Male Sex Reversal in the Japanese Frog Glandirana rugosa
by Ikuo Miura, Yoshinori Hasegawa, Michihiko Ito, Tariq Ezaz and Mitsuaki Ogata
Biomolecules 2024, 14(12), 1566; https://doi.org/10.3390/biom14121566 - 9 Dec 2024
Viewed by 7212
Abstract
Sox3 is an ancestral homologous gene of the male-determining Sry in eutherian mammals and determines maleness in medaka fish. In the Japanese frog, Glandirana rugosa, Sox3 is located on the Z and W chromosomes. To assess the sex-determining function of Sox3 in [...] Read more.
Sox3 is an ancestral homologous gene of the male-determining Sry in eutherian mammals and determines maleness in medaka fish. In the Japanese frog, Glandirana rugosa, Sox3 is located on the Z and W chromosomes. To assess the sex-determining function of Sox3 in this frog, we investigated its expression in gonads during early tadpole development and conducted genome-editing experiments. We found that the Sox3 mRNA levels in the gonads/mesonephroi were much higher in ZW females than that in ZZ males, and that the W-borne allele was dominantly expressed. A higher expression in ZW females preceded the onset of the sexually dimorphic expression of other autosomal sex differentiation genes. The Sox3 protein was detected by immunostaining in the somatic cells of early tadpole gonads around the boundary between the medulla and cortex in ZW females, whereas it was outside the gonads in ZZ males. Disrupting Sox3 using TALEN, which targets two distinct sites, generated sex-reversed ZW males and hermaphrodites, whereas no sex reversal was observed in ZZ males. These results suggest that the sex-linked Sox3 is involved in female determination in the ZZ-ZW sex-determining system of the frog, an exact opposite function to the male determination of medaka Sox3y and eutherian Sry. Full article
(This article belongs to the Special Issue Molecular Insights into Sex and Evolution)
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