Thermogenomic Analysis of Left-Handed Z-DNA Propensities in Genomes

The initial discovery of left-handed Z-DNA was met with great excitement as a dramatic alternative to the right-handed double-helical conformation of canonical B-DNA. In this chapter, we describe the workings of the program ZHUNT as a computational approach to mapping Z-DNA in genomic sequences using a rigorous thermodynamic model for the transition between the two conformations (the B-Z transition). The discussion starts with a brief summary of the structural properties that differentiate Z- from B-DNA, focusing on those properties that are particularly relevant to the B-Z transition and the junction that splices a left- to right-handed DNA duplex. We then derive the statistical mechanics (SM) analysis of the zipper model that describes the cooperative B-Z transition and show that this analysis very accurately simulates this behavior of naturally occurring sequences that are induced to undergo the B-Z transition through negative supercoiling. A description of the ZHUNT algorithm and its validation are presented, followed by how the program had been applied for genomic and phylogenomic analyses in the past and how a user can access the online version of the program. Finally, we present a new version of ZHUNT (called mZHUNT) that has been parameterized to analyze sequences that contain 5-methylcytosine bases and compare the results of the ZHUNT and mZHUNT analyses on native and methylated yeast chromosome 1.