DNA commonly is viewed as an evenly spaced double helix and often depicted simply as a string of letters or even as two parallel lines. Genomes typically are analyzed by treating DNA sequences as if they actually were composed of strings of letters. In addition, both evolutionary biologists and computational biologists often make the assumption that all genetic variation is generated in a random manner. In reality, however, the structure of DNA is not monotonous, but rather varies along its sequence, sometimes dramatically so. Such variation in structure leads to sequence-dependent variations in the fidelity of DNA copying and repair. That the probability of distinct classes of mutations varies along a DNA sequence has implications for evolutionary theory because selection acts on heritable variation when this variation affects fitness. Highly mutable sequences have, in fact, evolved in genome regions such as those encoding pathogen coats, where increased diversity in a population favors survival. In addition, the fidelity of DNA replication and repair is affected by the activities of multiple enzymes (which can be induced by environmental or cell-type specific factors), and furthermore, it is becoming increasingly obvious that some of the information in DNA is carried in forms that can be obscured by treating DNA as if it actually were comprised only of a sequence of letters. Often it is the conformation of DNA (or RNA) or the relationship among sequences that carries the information. It is factors such as these that will be the focus of the Genome Structure and Variation Conference. A broad interdisciplinary group of researchers will gather to explore the impact of our increasing understanding of DNA structure, repair, replication, and organization on subjects ranging from evolution and the dependence of the effect of mutagens on environmental and sequence context to non-canonical forms of information representation in genomes. Incorporating our knowledge of the sequence-dependent effects of DNA structure and context on the analysis of genome sequence and variation is a computational challenge. However, in order for new methods to be developed, the appropriate communities must be made aware of the existence of novel biochemical and genetic observations on the one hand, and the potential for creation of novel computational tools on the other. By bringing together experts in these different areas to share ideas and begin a dialog, this workshop should serve as a catalyst for new collaborations and insights, along with the development of algorithms that will enable us to discover novel ways in which information affecting genetic variation and regulation is represented within genomes. In addition, this meeting is designed to facilitate productive interactions between early-career scientists, including graduate students, and the leading researchers at the conference.
|Effective start/end date||10/1/10 → 9/30/11|
- National Science Foundation (National Science Foundation (NSF))