Computational Molecular Biology 2024, Vol.14, No.5, 202-210 http://bioscipublisher.com/index.php/cmb 208 evolutionary novelties, particularly in developmental pathways. In Drosophila, new genes have rapidly evolved essential functions, challenging the traditional view of conserved genetic bases in development. The modular and hierarchical recruitment of protein domains has also been highlighted as a key mechanism in the evolution of protein functions. RNA-based gene duplication has emerged as a significant source of new functional genes, particularly in mammalian genomes. The birth of new genes through various mechanisms, including gene duplication and retroposition, has been a major driver of adaptive evolutionary innovations. The recruitment of genes into complex traits, such as C4 photosynthesis, often shows a bias towards certain gene lineages, indicating that some genes are more predisposed to new functions. The temporal flexibility of gene regulatory networks (GRNs) allows for the independent recruitment of genes, facilitating the evolution of novel traits. Finally, the burst of retroposition in primates has led to the emergence of new human genes, particularly those involved in spermatogenesis. Despite the progress in understanding new gene recruitment, several challenges remain. One major challenge is the accurate inference of gene ages and the annotation of their protein-coding potential. Different methods yield varying results, and there is a need for more reliable and consistent approaches. Another challenge is the functional characterization of new genes, particularly distinguishing between true functional genes and pseudogenes. This requires comprehensive experimental validation, which is often resource-intensive. The integration of new genes into existing GGI networks and their gradual acquisition of essential functions also pose challenges in terms of understanding the underlying mechanisms and evolutionary pressures. Additionally, the study of functional shifts and the co-option of genes in developmental pathways requires a detailed understanding of the historical sequence of events and the selective pressures involved. The rapid evolution of new genes in model organisms like Drosophila raises questions about the generalizability of these findings to other species. The modular and hierarchical nature of protein domain recruitment adds another layer of complexity to the functional characterization of new genes. Finally, the study of RNA-based gene duplication and retroposition requires advanced genomic and transcriptomic analyses to uncover the full extent of their contributions to new gene functions. Future research should focus on developing more accurate and reliable methods for inferring gene ages and annotating protein-coding potential. Integrating multiple approaches and validating results through experimental data will be crucial. There is also a need for comprehensive functional characterization of new genes, including high-throughput experimental validation and detailed phenotypic analyses. Understanding the mechanisms of new gene integration into GGI networks and their evolutionary significance will require advanced computational models and network analyses. Research should also explore the historical sequence of co-option and duplication events to better understand functional shifts in developmental pathways. Expanding studies to a broader range of species will help determine the generalizability of findings from model organisms. Investigating the modular and hierarchical recruitment of protein domains will provide deeper insights into the evolution of protein functions. Finally, future studies should leverage advanced genomic and transcriptomic technologies to uncover the full extent of RNA-based gene duplication and retroposition in generating new functional genes. Acknowledgments The author extends heartfelt thanks to Senior Researcher J.Q. Li for reviewing this paper multiple times and providing valuable revision suggestions. The author also wishes to thank the two anonymous peer reviewers for their insightful comments and constructive recommendations on this paper. Conflict of Interest Disclosure The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Abdol A., Röttinger É., Jansson F., and Kaandorp J., 2017, A novel technique to combine and analyse spatial and temporal expression datasets: a case study with the sea anemone Nematostella vectensis to identify potential gene interactions, Developmental Biology, 428(1): 204-214. https://doi.org/10.1016/j.ydbio.2017.06.004
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