Replication rate-information storage trade-off shapes genome architecture across domains

Abstract

Genome size varies widely among organisms, from compact genomes of bacteria to vast and complex genomes of eukaryotes. In this study, we theoretically identify the evolutionary pressures that may have driven this divergence in genome size. We use a parameter-free model to study genome size evolution under selection pressure to minimize replication time and maximize information storage capacity. We substantiate this choice by demonstrating a correlation between replication time and genome size using literature data. We show that bacteria tend to reduce genome size, constrained by a single replication origin, while eukaryotes expand their genomes by incorporating multiple replication origins. We propose a connection between genome size and cellular energetics, suggesting that endosymbiotic organelles, mitochondria and chloroplasts, evolutionarily regulate the number of replication origins, thereby influencing genome size in eukaryotes. We substantiate this claim by showing a correlation between organelle count and genome size data. We argue that nucleotide skews, present in nearly all genomes studied, and are used to identify replication origins, directly influence DNA unzipping kinetics, and hence its replication time. This connection enables us to derive nearly universal observations, such as Chargaffs second parity rule and replichore symmetrization, as adaptive consequences. We argue that high skews lead to faster replication, and substantiate it by showing a correlation between skews and replication speed in bacteria. The model reproduces more evolutionary genomic observations, such as a general preference for deletions over insertions across domains, and elongation and high variance of genome size under reduced selection pressure for replication rate, an integral component of C-value paradox. We highlight the possibility of regulation of the firing of latent replication origins in response to cues from the extracellular environment, leading to the regulation of cell cycle rates in multicellular eukaryotes. Significance StatementUnderstanding the forces shaping genome architecture is a long-standing challenge in evolutionary biology. Our study demonstrates that the balance between replication speed, influenced by nucleotide skews, and information storage, constrained by cellular energetics, drives the divergence in genome size between bacteria and eukaryotes. By quantifying selection pressure as the ratio of replication time to genomic information storage capacity, we show that this pressure enforces adaptive constraints, giving rise to observed features such as symmetric replichores and Chargaffs second parity rule. These insights not only help us resolve an enduring evolutionary puzzle, but also offer a unified framework linking genome organization, cellular specialization, and even potential mechanisms underlying carcinogenesis.