Integrative Computational Biomedical Approaches to Comparative Genomic Analysis Integrative Computational & Biomedical Approaches to Comparative Genomic Analysis One of the grand challenges in biology has been finding how alterations in the library of genes, or genome, of each organism, is responsible for the differences between species during evolution as well as the differences between individuals in a species, such as why some people are tall and others are short. The differences between species include changes in body shape, such as the length of the limbs or shape of the skull, overall size, behavior, and external coloration. Recently, with the development of affordable new technologies to quickly decode the genome, we have been able to look at both the portions of the genome that code for proteins and RNAbased enzymes in the cells, as well as the regions in and around the genes that control when, where, and at what level they will be expressed. These new technologies are also allowing researchers to move beyond a limited set of model organisms, such as the fruit fly and the mouse, to look at animals that are natural experiments taking place over the past few hundred million years. One of these natural experiments, like Darwins finches, are the anole lizards. The lizards in the genus Anolis represent the world's most species-rich genus in land-dwelling animals, with over 375 described species. Evolutionary biologist hypothesize that these species have arisen when a single population of lizards have invaded an island, and over millions of years, they have diverged to occupy different ecological niches, such as in the crown of trees, trunks, or underlying shrubs and grass. Building on the sequencing of the complete genome of the first anole, the Carolina green anole Anolis carolinensis, our group has been able to highlight important gene information as well as complete the sequencing of three more anole lizards, the grass anole, A. auratus, the slender anole, A. apletophallus, and the Central American giant anole, A. frenatus. We have been able to compare physical traits between these anoles and use computer-based tools to match them with changes in the genome. Developing these tools will also be useful for the new study of evolutionary medicine, which aims to take advantage of these insights to provide clues to doctors as to whether a change in the patients genome is likely to account for the genetic disease. The challenge is to combine the talents of computer scientists and biologists to develop the next generation of tools to allow these evolutionary medical comparisons. Anole lizards, like other reptiles, are also capable of regenerating their tails when lost. This is in contrast to humans who have lost almost all major regenerative capacity, except in a newborn state. We have used our knowledge of the lizard genome and tools to look at which genes are on versus off. Almost all of these genes are shared between lizards and humans, so the question focuses on what has changed in these genes and how they talk to each other that allow lizards to regenerate but not humans. Understanding and deciphering the network of interactions between genes is a huge undertaking and also would benefit from the combined efforts of statisticians/computer scientists and biologists to develop tools for these comparisons. For both the evolutionary medicine and regenerative medicine studies based in the anole lizards, I have started collaboration with Dr. Joshua Ho, a computer scientist at the Victor Chang Cardiac Research Institute, to work on using the newest generation of tools to address these questions.
|Effective start/end date||5/16/14 → 12/31/15|
- Burroughs Wellcome Fund: $10,000.00
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