Since the Darwin era, biologists have been paying attention to an important question-how did living things evolve from a common ancestor into a rich and diverse species? The production of new genes is an important source of biological evolution and the formation of species diversity. The study of the origin mechanism of new genes is essentially to explore the root of life evolution, but at the molecular level, how are new genes retained and integrated into existing network pathways to adapt to biological evolution What contribution has been made has not yet been well studied.
Ichthyology and Biogeography, Institute of Hydrobiology, Chinese Academy of Sciences, through comparative analysis of fish genomes, identified a new model organism in zebrafish The chiron gene (chiron), the first systematic study of the origin, evolution, expression pattern, molecular function, and signal pathway integration process of the new gene, and further explored the aquatic environment of Danoninae fish in Southeast Asia The molecular mechanism that produces a broad range of adaptive evolution.
About 48 to 54 million years ago, a highly conserved housekeeping gene—Nicotinamide phosphoribosy transferase, NAMPT) through the inversion seat process to form cDNA and insert it into other positions in the genome. By recruiting a protein coding sequence in its upstream region, a new chimeric protein gene is formed, which is called the ancestral chiron. gene. About 1 to 4 million years ago, the chiron gene used the Innovation-Amplification-Divergence (IAD) model to specifically produce 5 duplicate copies (chiron1-5) in zebrafish. Gene expression data prove that the chrion gene may originate in the early embryonic development process, and as its function evolves, its expression site gradually extends to the testis. Cell experiments have proved that the chrion protein has the function of NAD+ rate-limiting enzyme, which can effectively increase the level of NAD+ in the cell. Through Morpholino knockdown and CRISPR-Cas9 gene editing technology, the researchers proved that chiron is an essential gene for zebrafish embryo development. This result adds new evidence for the functional study of new genes in fish (Figure 1).
Further research found that the new gene chiron directly catalyzes the rate-limiting reaction of NAD+, integrates into the ancient core network NAD+ synthesis pathway, and promotes the signal pathway. Two energy metabolism genes, nmnat1 and naprt, are positively selected in fish, thereby systematically driving the co-evolution of the entire NAD+ biosynthetic pathway (Figure 2).
NAD+ is an important cofactor, which plays an important role in the process of metabolism. When energy is scarce (such as sugar deficiency, fasting, calorie restriction and exercise), the expression level of NAD+ will increase significantly. Therefore, by regulating the level of NAD+, the chiron gene may play an important role in physiological homeostasis. By continuously maintaining the level of NAD+ in the cell, the adequacy of NAD+ is ensured, and the response of the fish group to different groups is further improved. The adaptability of the ecological environment, especially in the critical period of food shortage and energy shortage. In addition, studies have shown that increasing NAD+ can delay mammalian aging and prolong lifespan. Then, the use of the new gene chiron to systematically improve the entire NAD+ synthesis pathway (nmnat1 and naprt) provides new ideas for increasing the NAD+ level of cells, and may further promote human anti-aging and life-prolonging research in biomedical fields.
related research results titled The new chimeric chiron genes evolved essential roles in zebrafish embryonic development by regulating NAD+ levels, published online in Science China Life Sciences. The research was completed by Dr. Fang Chengchi and others. The Institute of Hydrobiology was the first to complete, and the researcher of the Institute of Hydrobiology He Shunping was the corresponding author of the paper. The research work was awarded the Strategic Leading Science and Technology Special Project of the Chinese Academy of Sciences (Category B), the National Natural Science Foundation of China, the National Natural Science Foundation of China, and the National Natural Science Foundation of China. Supported by the National Science Foundation Youth Fund and other projects. In addition, this research has also attracted the attention of scholars in the field of evolution. Long Manyuan, a professor in the Department of Ecology and Evolution at the University of Chicago, made a comment on the topic A zebrafish-specific chimeric gene evolved essential developmental functions:discussion of conceptual significance. , Published in Science China Life Sciences.
Figure 1. The origin and function of the new gene chiron
Figure 2. The new gene chiron promotes the co-evolution of the NAD+ synthesis pathway