Genovation · Orphan Genes as Drivers of Evolutionary Innovation in Microbial and Bacteriophage Systems

Orphan genes, unique to an organism or evolutionary lineage, are fundamental drivers of biological innovation. Representing up to 20% of genomes—from microbes to primates—these novel genes enable species-specific adaptations through their diverse functions. However, most orphan genes remain uncharacterized, and the evolutionary pressures governing their emergence are unknown. Addressing these knowledge gaps is crucial for revealing how novel genetic material shapes evolution and biodiversity, particularly in microbial systems.The Genovation project aims to transform our understanding of gene birth and evolutionary innovation through three aims:1.Evaluate the fitness impact of newly emerged genes in bacterial and yeast species.2.Investigate how novel proteins integrate into cellular systems.3.Elucidate biological functions of successful gene birth events, focusing on the phage-bacteria arms race—where gene birth is highly prevalent.We will study both synthetic and natural genes to reveal complementary aspects of orphan gene biology. In Aims 1 and 2, we will use my experience with randomly generated nucleotide sequences to simulate early stages of orphan gene emergence in varied genetic backgrounds. Analyzing fitness changes, physiological effects, and protein interactions will provide insights into the relationships between genetic features, cellular contexts, and gene birth. Aim 3 will leverage the rapid evolution and abundance of orphan genes in viral genomes. By identifying orphan genes affecting the phage life cycle and characterizing their functions, we aim to uncover how these genes shape viral-host dynamics and drive novelty.This project builds on my expertise in large-scale techniques, microbial and phage genetics, and molecular biology methods. The Genovation project promises to yield insights into the mechanisms of evolutionary innovation, potentially opening new avenues in protein design, cellular engineering, and phage-based therapies.