A New Framework for Studying the Isochore Evolution: Estimation of the Equilibrium GC Content Based on the Temporal Mutation Rate Model

Isochore is the genome-wide mosaic structure in guanine-cytosine (GC) content. The origin of isochores is thought to have emerged in the ancestral amniote genome, and the GC-rich isochore is eroded in the mammalian lineages. However, there are many enigmas in the isochore evolution: 1) although all the mammalians, birds, and even reptiles, which are clearly polyphyletic, have isochore, opossum and platypus lack GC-rich and GC-poor isochore classes; 2) although the isochore is predicted to vanish according to a fairly robust theory, a completely opposite conclusion was led in some mammalian lineages; and 3) the major three hypotheses on the isochore evolution cannot explain observed evidences without flaws. So far compositional evolution has been studied under the assumption that per base pair rate of GC→AT (u) and AT→GC (v) mutations are temporally constant (the constant model). With this model alone, however, it is difficult to explain the isochore evolution. We propose a simple model for compositional evolution based on the temporal per base pair rate of mutations (the variable model). In this model, rates u and v vary depending on temporal GC contents. Mathematically, the variable model is an expansion of the constant model. By using high-density human single nucleotide polymorphism data, we compared the variable model with the constant model. Although the variable model gave consistent results with the constant model, it can potentially describe the complicated isochore evolution, which the constant model cannot explain. The versatile characteristics of the variable model may shed new light on the mysterious isochore evolution.