A significant challenge for biologists is understanding the genetic basis of variation among organisms. Meeting this challenge will require numerous organisms to become "genomically enabled", that is having a large number of genetic markers spread evenly throughout the genome that can be assembled into a genetic map. This will allow researchers to move very quickly from roughly locating a gene on a chromosome to identifying DNA sequences. In the past, developing these tools was time consuming and very expensive. The goal of this project is to develop a clear set of protocols and computational software to rapidly produce genomic analysis tools for just about any organism. After first testing the protocols on the well-developed model nematode worm, Caenorhabditis elegans, the techniques will be further refined by applying them to a non-model vertebrate organism, the pipefish Syngnathus scovelli. The research on these two organisms will serve as test cases from which an easily followed set of methods will be created and distributed widely, including the wet lab procedures for data generation and the software for the analysis of these data.
This research will have broad impacts by increasing the number of researchers who can genomically enable the organisms they study. This will lead to a more general set of answers to classic unanswered questions such as what genes and alleles are contributing to evolutionary change. In addition these tools will help biologists tackle practical problems such as what is the genomic basis of how organisms respond to climate change, a fundamental problem of our time.
Biologists are working tirelessly to understand the genetic and developmental underpinnings of evolutionary change in natural populations. This research is of particular importance given the rapid change in environmental conditions experienced by many organisms that are forcing them to adapt or become extinct. Scientists are beginning to address this research challenge using a small number of traditional laboratory model organisms such as fruit flies or mice. However, to make more general discoveries will require numerous other organisms living in the wild to become ‘genomically enabled’. Accomplishing this task will often entail the creation of an assembly of the complete DNA sequence of an organism’s genome. The overall goal of this grant was to create a clear set of protocols and computational tools to enable biologists to better create these genomic resources for nearly any study organism. We tackled this challenge by using four diverse organisms as test cases. We performed this work using two vertebrate animals and two invertebrate animals that are the focus of genetic studies at the University of Oregon. For two of these animals, the threespine stickleback fish and the common laboratory roundworm, extensive genomic resources already existed. The two other organisms, a pipefish and a nonstandard laboratory roundworm, had few genomic resources available when we began our project. The first two organisms provided an appropriate positive control for our approaches, while the second two were our test cases. For each organism we developed new laboratory genetic protocols and analysis software to create a high quality genome assembly that was well annotated for the genes present. In addition to providing new biological knowledge in terms of novel genomes, we also accomplished broader impact goals of this project beyond the scientific discoveries. This research served as a successful test case from which we created new protocols that have been distributed widely, including the wet lab procedures for data generation and software for the analysis of these data. We produced several laboratory protocols for genome assembly and annotation, and we produced the widely used Stacks software package to assist other researchers. Together, the results of this project have helped many other biologists by increasing their ability to genomically enabled their focal organism. This project also provided opportunities for undergraduate and graduate students to acquire computational biology training, and several of these students were drawn from groups underrepresented in the sciences. Lastly, PI Cresko gave numerous talks to general audiences on the fundamental breakthroughs in evolutionary biology, and the contribution of evolutionary understanding to everyday life, such as understanding the genetic basis of evolution in the wild.
