One of the most important questions in evolutionary biology is the molecular genetic basis of biological diversity. Research in the Zhao lab is focused on the mechanisms that contribute to the diversity of species, and the molecular changes underlying phenotypic divergence and adaptation. The Zhao lab is interested in  a number of questions. For example,

1) how do newly evolved genes (e.g. de novo genes and duplicated genes) originate, spread, and contribute to adaptive evolution?

2) how do gene expression differences affect other downstream phenotypes?

3) what is the genetic basis of local adaptation in natural populations?

To address these questions, the Zhao lab employs a wide spectrum of next-generation sequencing, computational, and analytical approaches to generate and study large-scale population genomic and transcriptomic data in systems of interest, including Drosophila and humans. The hypotheses generated from these data-rich analyses are to be tested using cutting edge genetic and experimental manipulations.

Recent work has suggested an alternative path to genetic novelty whereby de novo originated genes may be co-opted into function from ancestrally non-coding sequences in many species and taxa (including humans). However, nothing was known about the earliest birth process of de novo gene origination within species. Using genomic and population analyses, Dr. Zhao and colleagues have revealed that a large number of de novo genes segregating and evolving in Drosophila melanogaster populations under the influence of directional selection. Dr. Zhao has now expanded her analyses to identify de novo genes that contribute in multiple tissues and at different developmental stages. She aims to compile the first comprehensive description of de novo gene evolution within a species. Using CRISPR-Cas9 and other technology, her lab also is investigating the functions of the de novo genes. Dr. Zhao hopes to use genomic and genetic tools to study gene and genome evolution, as well as human cancer biology, from novel gene perspective, and provides insights into the mechanism of the origin and spread of de novo genes.

Another major focus of her lab is how species adapt to variable environments. To better understand the role of natural selection in the maintenance of expression variation within and between species, Dr. Zhao’s research focuses on parallel evolution of gene expression in heterogeneous environments. In a recent study, Dr. Zhao and colleagues observed substantial parallelism in expression differences and expression plasticity between natural populations, supporting the idea that spatially varying selection correlated with natural environments contributes to the maintenance of gene expression variation in these species. The Zhao lab will extend this work to the genetics of selectively maintained gene expression variation by carrying out a detailed investigation of genomic variation, transcriptomic variation, and variation in transcription factor binding in Drosophila populations using flies collected from a variety of environments.