Reconciling Natural Selection and Neutral Theory—It’s About Escaping Deaths, Not Maximizing Fitness

We propose a Unified Model (UM) that integrates natural selection and neutral theory of molecular evolution. This model advocates that lethal variations are perpetual threats to the sustained survival of all life forms in constantly changing environments, and bottlenecked reproduction is a natural selection solution preserved and fortified throughout evolution to rein in lethal variations. For brevity, the current review focuses on haploid bacteria only, leaving discussions on other life forms for separate future deliberations. We will attempt to illustrate the omnipresence of lethal variations in bacterial populations, and explain why bottlenecked reproduction is essential for not only weeding out obligately lethal mutations real-time, but also unmasking conditionally lethal variations under varying environments. Testing predictions of this new model is likely to lead to paradigm-shifting understanding of evolution at both molecular and phenotypic levels.