The origin of the primary X/Y sex chromosome and its evolutionary mechanism

Recently, the team of academician Gui Jianfang of the Institute of Hydrobiology of the Chinese Academy of Sciences and the team of Professor Mei Jie of the College of Fisheries of Huazhong Agricultural University revealed the evolutionary mechanism
of primary sex chromosomes driving the origin of X/Y sex chromosomes through autosomal fusion and chromatin remodeling in sexually plastic fish 。 The research results were published online in National Science Review
under the title "Origin and chromatin remodelling of young X/Y sex chromosomes in catfish with sexual plasticity".

Due to their special and diverse evolutionary trajectories, sex chromosomes have always been a fascinating research hotspot
in evolutionary biology and developmental biology.
Unlike mammals and birds, which have obviously differentiated atypic sex chromosomes, the sex chromosomes of most fish are still in the early stage of evolution, and the presence of atypic sex chromosomes is currently observed in less than 1% of teleost fish, which also makes fish have a variety of sex determination mechanisms, including genetic sex determination (GSD), environmental sex determination (ESD) and GSD+ESD, showing extraordinary sex plasticity
。 However, most current sex chromosome research focuses on heterosexual chromosomes, and it is difficult to accurately distinguish and assemble X and Y chromosomes with a low degree of differentiation, which makes the mechanism driving the establishment of "young" sex chromosome recombination inhibition and sex chromosome plasticity still unclear
。 Pelteobagrus fulvidraco is a Siluriformes Bagridae fish, which is a relatively stable type of genetic sex determination, and artificial induced reversal prompts yellowtail fish to be more sensitive to environmental factors (temperature), and high temperature can overwhelm the role of genetic sex determination; This makes the yellowtail an ideal model for studying the association between genetic sex determination and environmental sex determination in fish and their regulatory mechanisms (Science China Life Sciences, 2020, 63:157-159).

After years of cooperation, the research team created the XX pseudomale and all-female matching lines of the yellowtail fish through the conversion mechanism of genetic and temperature sex determination, which provided breeding materials for the sexual control breeding of yellowtail fish (Aquaculture, 2022, 560:738471).

Based on the early breeding of YY supermale yellowtail fish, the research team sequenced and assembled XX and YY yellowtail fish, and successfully obtained high-quality X and Y chromosome sequences and located about 300 kb of sex-determined regions (SDRs).

Through the comparative analysis of X and Y chromosomes, it was found that the sequence difference of X and Y chromosomes of Yellow Jaw fish was only less than 1%, and no chromosome rearrangement and evolutionary fault were observed, indicating that the sex chromosomes of Yellow Jaw fish were still in the early stage
of evolution.
In addition, X and Y chromosomes have the same gene collinearity and similar repeat ratios, and only some Y chromosome-specific SNPs, INDELs, and transposable elements
exist.
This finding supports the theory that chromosome rearrangement is a consequence rather than a cause of recombination inhibition, and suggests that sex-specific mutations and transposable elements may be the main driving force for
the establishment of sex chromosome recombination inhibition.
At the same time, the previously reported sex determination candidate gene pfpdz1 is located in the SDR (Science Bulletin, 2018, 63:1420-1430), and Y-specific DNA transposon and LTR were found in the intron region of the gene, which may be involved in sex determination
through transposon-mediated epiregulation.

In addition, the study found that catfish may have frequent sex chromosome switching by comparing four known sex chromosomes, which also provides an explanation
for the low degree of general differentiation of sex chromosomes in catfish order catfish.
Notably, the study found that the sex chromosomes of yellowtail fish may have originated from the fusion of two autosomes, and a highly rearranged region (HRR) was formed downstream of the fusion site, and the SDR was located just in the center of this region, indicating that frequent chromosomal rearrangement events may have contributed to the emergence of SDR (Figure 1).

Fig.
1 Origin and evolution of sex chromosomes in yellowtail fish

Through three-dimensional genome analysis, it was found that the Y chromosome of yellowtail fish has a looser three-dimensional structure and a relatively higher gene expression level
than the X chromosome.
The study also observed significant cis-interaction of Y chromosome SDR, and significant trans regulation
of X and Y chromosomes with autosomal genes involved in maintaining physiological activity in both males and females, respectively.
Interestingly, after using the aromatase inhibitor letrozole treatment to induce sexual reversal of XX female yellowtail fish to XX pseudomale, their X chromosome (X^M) exhibits a highly similar three-dimensional structure, intranuclear chromosome arrangement, accompanied by similar gene expression patterns
.
This suggests that the special three-dimensional conformation of the X and Y chromosomes plays an important role in maintaining gender stability (Figure 2).

Fig.
2 Three-dimensional structural remodeling and dynamic gene expression of sex chromosomes in yellowtail fish

In summary, through the detailed analysis of high-quality assembled X and Y chromosomes, their sequence characteristics and chromatin configuration, this study provides new insights into the origin of early sex chromosomes, the formation of recombination inhibition, and the three-dimensional structural reconstruction of sex chromatin driven by fish sex plasticity (Figure 3), and also provides new ideas
for the creation of fish sex remodeling technology and sex control breeding based on the three-dimensional structural remodeling of fish sex chromosomes.

Fig.
3 Evolution of sex chromosomes and three-dimensional structural remodeling model of yellowtail fish

Dr.
Gong Gaorui, College of Fisheries, Huazhong Agricultural University, is the first author of the paper, and Professor Mei Jie of the College of Fisheries and Academician Gui Jianfang of the Institute of Aquatic Sciences are the corresponding authors
of the paper.
Associate Researcher Li Xiyin, Dr.
Lin Qiaohong, Dr.
Dan Cheng and Zhou Li from the Institute of Aquatic Sciences participated in the research
.
The research was supported
by the National Natural Science Foundation of China, the National Modern Agricultural Industry Technology System, the National Key Research and Development Program, Hubei Hongshan Laboratory, and the Hubei Outstanding Youth Fund.

Links to papers: https://doi.
org/10.
1093/nsr/nwac239