Comparative analysis of teleost fish genomes reveals preservation of different ancient clock duplicates in different fishes

摘要

Clock (Circadian locomotor output cycle kaput) was the first vertebrate circadian clock gene identified in amouse forward genetics mutagenesis screen. It encodes a bHLH-PAS protein that is highly conservedthroughout evolution. Tetrapods also have the second Clock gene, Clock2 or Npas2 (Neuronal PAS domainprotein 2). Conversely, the fruit fly, an invertebrate, has only one clock gene. Interrogation of the five teleostfish genome databases revealed that the zebrafish and the Japanese pufferfish (fugu) each have three clockgenes, whereas the green spotted pufferfish (tetraodon), the Japanese medaka fish and the three-spinestickleback each have two clock genes. Phylogenetic and splice site analyses indicated that zebrafish and fugueach have two clocks genes, clockla and clock] b and one clock2; tetraodon also have clockla and clockl b butdo not have clock2; and medaka and stickleback each have clocklb and one clock2. Genome neighborhoodanalysis further showed that docklalclockl b in zebrafish, fugu and tetraodon is an ancient duplicate. Whilethe dN/dS ratios of these three fish clock duplicates are all <1, indicating that purifying selection has actedupon them; the Tajima relative rate test showed that all three fish clock duplicates have asymmetricevolutionary rates, implicating that one of these duplicates have been under positive selection or relaxedfunctional constraint. These results support the view that teleost fish clock genes were generated from anancient genome-wide duplication, and differential gene loss after the duplication resulted in retention ofdifferent ancient duplicates in different teleost fishes, which could have contributed to the evolution of thedistinct fish circadian clock mechanisms.