Finding the switches that activate animal genes through a combined in silico and in vivo approach
The DNA sequences of genomes encode the recipes for making functional cellular products, notably proteins, and switches that regulate when these products are made. While the genetic code for proteins has been known for decades, a similar code for the regulative switches is lacking. This presents a major challenge to understanding the genetic basis of life, as these switches (called cis-regulatory elements or CREs) may outnumber protein-coding genes by 20-50 fold. Both in vivo and in silico approaches exist to study CREs, but the former approaches are generally low throughput and not up to the scale of vast genomes, and the latter lack validation of predictions. We are merging in silico and in vivo approaches to identify the CREs controlling genes responsible for a fruit fly pigmentation trait. Here, we are leveraging the knowledge of five CREs that switch on the transcription of five different genes from a fruit fly tergite pigmentation gene regulatory network (GRN). We are using the SCRMshaw bioinformatic tool to identify novel predicted CREs controlling genes within this GRN based on underlying similarities in the DNA sequences of the known CREs. From this novel list, we will test 24 for CRE activity in in vivo reporter transgene assays. The results from these tests will reveal to what extent the in silico method succeeded. Novel validated CREs will be compared with the known five to reveal what the molecular functions are for the common DNA motifs as the next stage of this research project. The encoding of information in CREs is a universal feature of life, so these results bear upon life at every level, including the betterment of the human condition.
Tom M Williams
Primary Advisor's Department
Stander Symposium poster
"Finding the switches that activate animal genes through a combined in silico and in vivo approach" (2019). Stander Symposium Posters. 1529.