Revisiting the Neutral Dynamics Derived Limiting Guanine-Cytosine Content Using the Human De Novo Point Mutation Data

TL;DR

This paper reevaluates the limiting GC content in the human genome under neutral evolution using de novo mutation data, introducing a new mutation bias measure and formula that accounts for CpG mutations, suggesting possible persistence of isochores.

Contribution

It presents a novel approach to estimate mutational bias and a new formula for limiting GC content that incorporates CpG mutations, advancing understanding of neutral genome dynamics.

Findings

GC content decreases less when CpG mutations are included

A new mutation bias measure facilitates dataset comparisons

Isochore-like structures may persist under neutral evolution

Abstract

We revisit the topic of human genome guanine-cytosine content under neutral evolution. For this study, the de novo mutation data within human is used to estimate mutational rate instead of using base substitution data between related species. We then define a new measure of mutation bias which separate the de novo mutation counts from the background guanine-cytosine content itself, making comparison between different datasets easier. We derive a new formula for calculating limiting guanine-cytosine content by separating CpG-involved mutational events as an independent variable. Using the formula when CpG-involved mutations are considered, the guanine-cytosine content drops less severely in the limit of neutral dynamics. We provide evidence, under certain assumptions, that an isochore-like structure might remain as a limiting configuration of the neutral mutational dynamics.