Groundbreaking Genomic Insights Unveil Master Sex-Determining Gene in the Central Bearded Dragon
In a remarkable scientific advancement, two independent research groups have simultaneously published near-complete, telomere-to-telomere genome assemblies of the Australian central bearded dragon (Pogona vitticeps), shedding light on the enigmatic mechanisms of sex determination in this species. Native to central eastern Australia and popular worldwide as pets, Pogona vitticeps exhibits an extraordinary blend of genetic and environmental sex determination, whereby incubation temperature can override chromosomal sex cues to flip an individual’s sex from male to female. This duality has long intrigued biologists, and the newly assembled reference genomes promise to revolutionize our understanding of vertebrate sex determination systems.
Unlike classical sex chromosome systems seen in mammals (XY) or birds (ZW), Pogona vitticeps employs a ZZ/ZW sex chromosome mechanism in which females are ZW heterogametic and males are ZZ homogametic. However, the notable twist in this system is the ability of genetic males (ZZ) to develop as phenotypic females when exposed to elevated nest temperatures during embryogenesis. This temperature-induced sex reversal presents a compelling scenario in which environmental factors modulate genetic programming at a molecular level, highlighting a complex interplay not well understood in reptilian species.
Advances in ultra-long read sequencing technologies have been pivotal in achieving the unprecedented quality of these genomic assemblies. One study, spearheaded by a consortium including BGI, the Chinese Academy of Sciences, and Zhejiang University, utilized a combination of DNBSEQ short reads and the novel CycloneSEQ nanopore sequencer—the first animal genome assembled with this technology. In parallel, an Australian team comprising researchers from the University of Canberra and collaborators from multiple esteemed institutions, employed PacBio HiFi, Oxford Nanopore ultralong reads, and Hi-C chromatin conformation capture sequencing to generate a complementary female genome assembly. Together, these resources enable unprecedented resolution of the Pogona vitticeps’ sex chromosomes.
The assemblies themselves are monumental achievements in genomic science. Both projects delivered high-contiguity genomes of approximately 1.75 gigabase pairs, with near-complete telomere to telomere coverage and minimal gaps confined predominantly to microchromosomes. Importantly, the sex chromosomes were fully assembled as single scaffolds, allowing research teams to delineate the pseudo-autosomal region (PAR) on chromosome 16 where Z and W chromosomes recombine. This level of chromosomal resolution is critical for dissecting sex-determining loci and understanding the evolutionary dynamics of sex chromosome differentiation.
Through comparative genomic analyses of the Z and W chromosomes, the studies identified a non-recombining sex determination region (SDR) enriched in candidate genes central to male sex differentiation. Foremost among these were the Anti-Müllerian hormone gene (Amh), its receptor (Amhr2), and the bone morphogenetic protein receptor 1A gene (Bmpr1a). Amh, well-known for its role in the regression of Müllerian ducts during vertebrate sexual development, exhibited a significant male-biased expression pattern across developmental stages, positioning it as the likely master sex-determining gene in the central bearded dragon.
Intriguingly, these findings diverge from classical models exemplified by mammals and birds, where dominant master sex-determining genes such as Sry or Dmrt1 drive sexual fate. To date, no analogous single sex-determining gene has been definitively identified in reptiles, making the discovery of Amh’s central role in Pogona vitticeps a landmark contribution. The dosage-sensitive presence of Amh and its receptor on the Z chromosome, existing in double copy in males (ZZ) and single copy in females (ZW), suggests a mechanism whereby gene dosage influences sexual fate, nuanced further by environmental temperature inputs.
Adding complexity, the transcription factor Nr5a1, located within the PAR, exhibited differential expression patterns implicating it in the modulation of Amh. Nr5a1 is known to bind regulatory regions of Amh, potentially orchestrating a gene regulatory network governing sex determination that integrates both chromosomal and hormonal signals. Such a multifactorial regulatory model underscores the intricate biological choreography underlying sex differentiation in this species.
The utilization of nanopore sequencing technologies, especially the CycloneSEQ platform, enabled the recovery of approximately 124 million base pairs of previously uncharacterized genomic sequences, enhancing annotation completeness. This additional genetic material contains numerous genes and regulatory elements critical for unraveling the mechanisms by which temperature influences sex determination, providing an unprecedented window into epigenetic and transcriptional modulation.
From a broader perspective, these genomic resources pave the way for accelerating research across vertebrate developmental biology and evolutionary genetics. Arthur Georges, senior author from the University of Canberra, articulated the significance of having such high-resolution squamate models available for comparative studies, bridging gaps with mammalian and avian model organisms. The insights gleaned here have profound implications for understanding gene-environment interactions, sexual development, and the evolution of sex chromosome systems.
In the Chinese-led project, Qiye Li from BGI emphasized the strategic choice of Pogona vitticeps to inaugurate their novel sequencing technology, aligning scientific innovation with cultural symbolism during China’s Year of the Dragon. The unbiased, ultra-long reads afforded by CycloneSEQ transcended traditional challenges posed by repetitive and GC-rich sequences, yielding a robust and contiguous assembly. Li also highlighted the complementary nature of the two independent datasets and the exciting prospects for exploring the evolutionary genesis of the ZW system in related species.
Noteworthy is the elevated confidence resulting from two separate teams converging independently on the same candidate master sex-determining genes. This concordance, underpinned by open data sharing, provides a solid foundation for subsequent functional studies. Nonetheless, several aspects of the regulatory network remain to be elucidated, particularly regarding the interactions among transcription factors and environmental cues guiding this unique sex determination process.
The convergence of high-throughput sequencing innovation and integrative biological inquiry embodied in these publications marks a transformative moment in vertebrate genomics. As the scientific community digests these findings, forthcoming research is poised to dissect mechanistic pathways, elucidate evolutionary trajectories, and harness this knowledge for broader biological and conservation applications. The central bearded dragon emerges not only as a fascinating evolutionary subject but also as a genomic beacon illuminating the complexities of sex determination.
A webinar featuring the lead authors, scheduled for 26th August at 10:00 am UTC, will offer attendees a unique opportunity to engage directly with the investigators and delve deeper into the nuances of this groundbreaking work.
Subject of Research: Animals
Article Title: A near telomere to telomere phased genome assembly and annotation for the Australian central bearded dragon
News Publication Date: 19-Aug-2025
References:
Guo Q, Pan Y, Dai W et al., A near-complete genome assembly of the bearded dragon Pogona vitticeps provides insights into the origin of Pogona sex chromosomes. GigaScience 2025.
Patel HR, Alreja K, Reis AML, et al., A near telomere to telomere phased genome assembly and annotation for the Australian central bearded dragon Pogona vitticeps. GigaScience 2025.
Image Credits: Duminda Dissanayake
Keywords: sex determination, Pogona vitticeps, bearded dragon, genome assembly, telomere-to-telomere sequencing, nanopore sequencing, CycloneSEQ, PacBio HiFi, ZZ/ZW sex chromosomes, Anti-Müllerian hormone, Amh, Amhr2, gene dosage, temperature-dependent sex determination
