Ancestral molecule from bacteria-like cells could offer evolutionary insight into sexual reproduction

A study by the Karolinska Institutet in Sweden, among others, presents the theory that egg-sperm fusion, a crucial feature of sexual reproduction in plants and animals, may stem from an ancient form of genetic exchange that involved the fusion of bacteria-like microorganisms. called archaea. The results, published in Nature Communicationcan open up an entirely new perspective on the evolution of sex.

Archaeal proteins with membrane fusion activity could help us understand how cells evolved from seemingly simple forms sharing discrete pieces of DNA to today’s complex life forms undergoing sexual reproduction.

Shunsuke Nishio, researcher at the Department of Biosciences and Nutrition, Karolinska Institutet, and one of the first authors of the study

The fusion of egg and sperm, specialized cells that carry genetic information for the next generation, is the culmination of sexual reproduction. Because uncontrolled cell fusion is deadly, plants and animals use special proteins called fusogens to control when and where this process takes place.

The new study reports that archaea, bacteria-like cells thought to have appeared more than 3 billion years ago, may contain a protein (Fusexin 1 or Fsx1) that resembles a type of fusogen (HAP2) that had already been identified in viruses, plants and invertebrate animals.

The researchers combined computational evolutionary biology, AlphaFold-based protein modeling, X-ray crystallography and functional studies to show that the archaeal protein Fsx1 is a true fusogen. This is both because it is structurally similar to the previously identified HAP2 fusogen and able to promote cell-cell fusion when expressed in other cell types.

“Gamete fusion has fascinated mankind for more than 150 years. As we already knew that HAP2-like proteins are used to fuse the membrane of enveloped viruses (such as zika, dengue and rubella) with host cells , we wondered if this key molecule originated in a virus and was then reused for the fusion of gametes in plants and animals or the other way around”, explains Luca Jovine, professor in the Department of Biosciences and Nutrition, Karolinska Institutet, and one of the study’s corresponding authors, he continues:

“The discovery that ancient creatures like archaea may also contain a HAP2-like protein now raises an intriguing third possibility that Fusexin1 is the ancestral molecule from which viral, plant, and invertebrate animal fusogens derive.”

The study was an international collaboration with academic research groups from Israel, Argentina, Uruguay and Switzerland, as well as the European Synchrotron Radiation Facility (ESRF) in France and the British intelligence society artificial DeepMind which developed AlphaFold.

The next step will be to determine what the Fsx1 proteins do in nature, for example, whether they fuse archaea cells – like their plant and animal counterparts HAP2 fuse gametes – to promote sex-like DNA exchange. Parallel studies will also be needed to accurately trace the evolutionary history linking Fsx1 and HAP2 in order to firmly establish their origin.

Karolinska Institutet’s work was funded by the Knut and Alice Wallenberg Foundation and the Swedish Research Council. Shunsuke Nishio and Luca Jovine report no conflicts of interest.


Journal reference:

Me, D. et al. (2022) Discovery of archaeal fusexins homologous to eukaryotic gamete fusion proteins HAP2/GCS1. Communication Nature.