Decoding genome recombination and sex reversal

Highlights

• The swamp eel is an increasingly recognized model organism for reproductive, developmental, and genetic studies.

• Whole genome-wide chromosome fission/fusion events occurred during speciation of the swamp eel, and probably contributed to species survival.

• Female transforms its sex naturally to male through an intersexual phase. Histologically, the ovary becomes a testis via a transition of ovotestis. Progenitors of germline stem cells can be identified in ovotestis, which have bipotential to differentiate into either male or female germline stem cells.

• The sex reversal process is involved in two molecular mechanisms, degradation of female germline cells by ubiquitination-dependent proteasome/phase separation, autophagy, and apoptosis, and spermatogenesis arrest due to dysregulation of histone-to-protamine replacement in ovotestis.

Over the past 440 years since the discovery of the medicinal value of swamp eels, much progress has been made in the study of their biology. The fish is emerging as an important model animal in sexual development, in addition to economic and pharmaceutical implications. Tracing genomic history that shapes speciation of the fish has led to discovery of the whole genome-wide chromosome fission/fusion events. Natural intersex differentiation is a compelling feature for sexual development research. Notably, identification of progenitors of germline stem cells that have bipotential to differentiate into either male or female germline stem cells provides new insight into sex reversal. Here, we review these advances that have propelled the field forwards and present unsolved issues that will guide future investigations to finally elucidate vertebrate sexual development using the new model.

Introduction

The swamp eel (Monopterus albus), also called the rice field eel, is an egg-laying freshwater fish that taxonomically belongs to the Synbranchidae family in the Synbranchiformes (Neoteleostei, Teleostei, Vertebrata) order. It is native to Asia and is found primarily in China, Thailand, Japan, Korea, Vietnam, Laos, Cambodia, Myanmar, India, Indonesia, Malaysia, Singapore, and Philippines; it is also observed in Australia and the USA [1]. There are over 30 common names for this species around the world, for example, rice eel, luon, pla lai, and belut. In point of fact, it needs a unifying, representative, and inclusive nomenclature. The name ‘swamp fish’ may better describe biological features of the species.

The swamp eel is an economically important freshwater fish in aquacultural production worldwide. It has high nutritional value, supplies rich protein for humans, and also is a good source of omega-6 polyunsaturated fatty acid. As early as the Ming Dynasty in ancient China in 1578, pharmacist Shi-Zhen Li described the medicinal value of swamp eel in treatment of numerous human diseases in the most influential pharmacy monograph, the Bencao Gangmu, a compendium of materia medica [2].

The teleost fish is an increasingly recognized model organism for biological studies [3]. Successful speciation of swamp eel depends on its unusual reproduction strategy, protogynous hermaphroditism. Natural sex reversal ensures successful establishment of new colonies during natural selection. Sex reversal in swamp eel was first reported in 1944 by Liu [4]. Three years later, Bullough made a comment on the discovery in Nature [5]. In the sex reversal process, an ovary transforms into a testis via ovotestis differentiation in an intersexual phase during its life cycle [6,7]. Exploration of the molecular mechanisms underlying the sex change is a major area of interest, thus swamp eel offers a powerful system for studying sexual development and adaptive evolution in vertebrates [8., 9., 10., 11.]. Since the description of the medicinal value of the species in 1578, important progress has been made over the past 443 years. Major advances include whole genome sequencing and de novo chromosome-scale assembly of the genome [12], discovery of the whole genome-wide chromosome fusion events during the speciation [13], identification of common progenitors of germline stem cells that differentiate into testis and ovary stem cells, unveiling of cell fate in intersex differentiation, and molecular and cellular mechanisms of sex reversal [14]. We want to highlight these advances that have propelled the field forwards and provided important insights into development and evolution in vertebrates.