Every species, population, or individual can be distinctly characterized by a unique set of genetic variations that define their genetic identity. Many of these inherited or recently acquired genetic variations may influence phenotypic outcomes through alterations in genome architecture, chromatin structure, gene expression, sequence, and function. Understanding how genes and genomes evolve is pivotal to elucidating the genetic foundation of the emergence and evolution of novel phenotypes, and, ultimately, life’s diversity. Furthermore, the impact of such genetic diversity on human health and disease has often been underemphasized. Research in the Zhao Lab employs a comprehensive array of techniques including genetics, genomics, single-cell -omics, biochemistry, phenotyping, behavior, deep learning, and computational structural biology to probe evolutionary innovations in Drosophila and humans.
1) The birth of new genes
Genes are essential functional units in every cell of all life forms. When we compare the genomes of different species, even closely related ones, we find that they often have different numbers of genes. This shows that gene gain and loss is a dynamic process in evolution. A central question is how new genes are born.
Most new genes arise through duplication-related processes. However, research breakthroughs in the last decade have shown that genes can also be born de novo from ancestrally non-genic sequences. The Zhao Lab is interested in both duplication-based and de novo mechanisms, and we are particularly focused on understanding the birth of de novo genes. De novo genes provide a unique paradigm for studying how genetic novelties arise from “junk DNA” and subsequently spread into populations and impact phenotypes and health.
We develop methods to identify genetic novelties using computational and genomic tools. We characterize new genes’ functions using genetic, biochemical, and phenotyping tools. We also work to determine the biochemical properties and functions of novel proteins using structural biology. Finally, we characterize the evolutionary forces shaping their emergence (population/evolutionary genetics).
Direction 1. How are de novo genes regulated?
Direction 2. What are the structures of de novo proteins, and how did they originate and evolve?
Direction 3. What are the functions of de novo genes, and how do they integrate into functional networks?
2) The basis of novel behaviors
Drosophila have long been model organisms for behavior and genetics, providing numerous insights into animal behavior. Our lab is interested in studying evolutionary novel behaviors, which are behaviors that have recently originated and diverged among species. Drosophila suzukii stands out as a fascinating subject for behavioral study. Unlike its close relatives, which predominantly lay eggs in rotten fruit, D. suzukii exhibits a distinct and recently evolved behavior: the preference for depositing eggs in ripe fruit. This shift in oviposition behavior has significant ecological and economic implications.
The adaptation of D. suzukii to exploit ripe fruits as egg-laying substrates underscores its evolutionary agility. It suggests a successful niche differentiation strategy, allowing the species to potentially avoid competition with other drosophilids and access an abundant food resource for its offspring. This adaptation also holds the potential to provide insights into broader topics like adaptive evolution, niche specialization, and behavioral plasticity. Our lab is currently pursuing this line of research in the non-model species D. suzukii. We are studying the neurogenetics of egg laying behavior in D. suzukii using custom-made behavioral assays, electrophysiology, and imaging tools.
Direction 1. What are the neural and sensory mechanisms underlying substrate preferences?
Direction 2. What genes are essential for the egg-laying behavior shift?
Direction 3. How did D. suzukii gradually shift its egg-laying behavior?