The integrated WF-Haldane (WFH) 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. Under-estimation of genetic drift is a major cause of mis-conclusions on 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 proposed the branching process for genetic drift (Haldane 1927), whereby each gene copy is transmitted toKdescendants with the mean and variance ofE(K) andV(K). Genetic drift is simplyV(K), i.e., the variance in transmission success, orV(K)/Nwhen averaged over the population. Under the WF model, many paradoxes have emerged: i) Most curiously, genetic drift may often become stronger asNbecomes larger at the ecological time scale, opposite to the model; ii) Sex chromosomes experience drift differently even with the same normalizedN; iii) Genetic drift operates on advantageous mutations depends onV(K) but not onN. iv) Irresolution and paradoxes emerge in multi-copy gene systems, including diploidy, viruses and others, whereby evolution progresses both within and between individuals. We now show that the integration of the WF and Haldane (i.e., WFH) model can resolve these paradoxes. Most important, the WFH model can fully define genetic drift in molecular evolution.