The Generalized Haldane (GH) model of genetic drift resolving the many paradoxes of molecular evolution

Genetic drift, the random changes in frequencies of neutral variants, is the fundamental force of molecular evolution. However, the standard Wright-Fisher (WF) model of random sampling in population of sizeNonly partially defines genetic drift with 1/Nor 1/N_e(N_ebeing a function of varyingN’s). In parallel, JBS Haldane (1927) proposed the branching process for genetic drift, whereby each gene copy is transmitted toKdescendants with the mean and variance ofE(K) andV(K). WhereasNis externally imposed on the standard and modified WF models, the Haldane model can be generalized (hence, the GH model) for regulatingN’s internally as a function ofE(K). The determination ofN, as well as the broader definition of genetic drift based onV(K), enables the GH model to account for many paradoxes of molecular evolution. They include: i) Genetic drift may often become stronger asNbecomes larger; ii) The two sexes experience drift differently; iii) Genetic drift operates on advantageous mutations is independent ofN; iv) Irresolution and paradoxes emerge in multi-copy gene systems (viruses, mitochondria, etc.) whereby genetic drift happens within and between individuals. We show how a GH model can resolve these paradoxes that elude the WF models. By integrating their results, GH models may supplant the WF models of genetic drift for the ever more complex biological systems.