Enhancer evolution as a driving force for lineage-specific paralog usage in the central nervous system

Abstract

Expression patterns of paralogous genes in the functionally homologous cells sometimes show differences across species. However, no reasonable explanation for the mechanism underlying such phenomena has been discovered. To understand this mechanism, the present study focused on the hypophysiotropic GnRH neurons in vertebrates as a model. These neurons express eithergnrh1orgnrh3paralogs depending on species, and apparent switching of the expressed paralogs in them occurred at least four times in vertebrate evolution. First, we found redundant expressions ofgnrh1andgnrh3in a single neuron in piranha and hypothesized that this situation may indicate an ancestral condition. We tested this hypothesis by examining the activity of piranhagnrh1/gnrh3enhancers in zebrafish and medaka, in which the twognrhparalogs are not co-expressed. Here, thegnrh1/gnrh3enhancer of piranha induced reporter RFP/GFP co-expressions in a single hypophysiotropic GnRH neuron in both zebrafish and medaka. From these results, we propose that long-lasting (~550 My) redundancy aftergnrh1/3duplication in 1R/2R WGD may be the key to apparent switching of the paralog usage among the present-day species. Moreover, interspecies analyses of enhancers indicated that the loss of enhancers rather than changes in trans-regulatory elements drove the role-division of these paralogs.