The paradox of extremely fast evolution driven in multi-copy gene systems - A resolution

Abstract

Multi-copy gene systems that evolve within, as well as between, individuals are common. They include viruses, mitochondrial DNAs, transposons and multi-gene families. The paradox is that their evolution in two stages should be far slower than single-copy systems but the opposite is often true. The paradox has been unresolvable because the standard Wright-Fisher (WF) model for molecular evolution cannot track multi-copy genes. We now apply the newly expanded WF-Haldane (WFH) model to such systems, first on ribosomal rRNA genes. On average, rRNAs have C ∼ 150 - 300 copies per haploid in mammals. While a neutral mutation would take 4 N ( N being the population size) generations to become fixed, the time should be 4 NC generations for rRNAs. However, the observed fixation time in mouse and human is < 4 N ; thus the paradox means, effectively, C < 1. Genetic drift (i.e., all random neutral forces driving molecular evolution by the WFH model) of rRNA genes appears 200-300 times higher than single-copy genes, thus reducing C to < 1. The large increases in genetic drift are driven by the homogenizing forces of unbiased gene conversion, unequal crossover and replication slippage within individuals. This study is one of the first applications of the WFH model to track random neutral forces of evolution. Such random forces, outside of the standard WF model, are often mis-interpreted as the working of natural selection.