Neofunctionalization of Duplicated Genes Under the Pressure of Gene Conversion

Abstract

Neofunctionalization occurs when a neofunctionalized allele is fixed in one of duplicated genes. This is a simple fixation process if duplicated genes accumulate mutations independently. However, the process is very complicated when duplicated genes undergo concerted evolution by gene conversion. Our simulations demonstrate that the process could be described with three distinct stages. First, a newly arisen neofunctionalized allele increases in frequency by selection, but gene conversion prevents its complete fixation. These two factors (selection and gene conversion) that work in opposite directions create an equilibrium, and the time during which the frequency of the neofunctionalized allele drifts around the equilibrium value is called the temporal equilibrium stage. During this temporal equilibrium stage, it is possible that gene conversion is inactivated by mutations, which allow the complete fixation of the neofunctionalized allele. And then, permanent neofunctionalization is achieved. This article develops basic population genetics theories on the process to permanent neofunctionalization under the pressure of gene conversion. We obtain the probability and time that the frequency of a newly arisen neofunctionalized allele reaches the equilibrium value. It is also found that during the temporal equilibrium stage, selection exhibits strong signature in the divergence in the DNA sequences between the duplicated genes. The spatial distribution of the divergence likely has a peak around the site targeted by selection. We provide an analytical expression of the pattern of divergence and apply it to the human red-and greenopsin genes. The theoretical prediction well fits the data when we assume that selection is operating for the two amino acid differences in exon 5, which are believed to account for the major part of the functional difference between the red and green opsins.

Whole-genome duplication in teleost fishes and its evolutionary consequences

“…Second, gene conversion can contribute to neofunctionalization, since beneficial mutations can be shared and also, novel combinations of allelic sequences can be created. In a theoretical model, Teshina and Innan have explored another interesting effect of gene conversion by which it counteracts neofunctionalization (Teshima and Innan, 2008). A DNA sequence conferring a novel function can be converted back to the ancestral sequence by gene conversion.…”

Population genetic models of duplicated genes

“…This might take time, so it is important to know whether this temporarily neofunctioned gene (pink box) can be maintained for a sufficiently long time, during which the two genes can accumulate mutations. Innan (2003b) proposed a two-locus model of this process, and found that the temporal state can be stably maintained when the power of selection to eliminate deleterious gene conversion is sufficiently stronger than the pressure of homogenization by gene conversion (see also Teshima and Innan 2008). In the model, it is assumed that chromosomes having two different alleles (i.e., AB and BA) are advantageous over those with a single kind (i.e., AA and BB).…”

Evidence that strong positive selection drives neofunctionalization in the tandemly duplicated polyhomeotic genes in Drosophila

“…The likely reason appears to be that gene conversion was at some point inactivated in the first introns of ph-p and ph-d, because of drastic sequence differences caused by insertion/deletion events (43). As a result, the first intron of ph-p (which is much larger than that of ph-d) contains several regulatory elements that may be potential targets of selection (in that they can escape the counteracting force of gene conversion).…”