STRUCTURAL ANALYSIS OF ETS-RELATED GENES IN LOWER EUKARYOTES

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Studies of ets family genes in lower eukaryotes focused on: 1) possible ets sequences in the baker's yeast (Saccharomyces cerevisiae); 2) an erg homolog in a sea urchin; 3) an inversion found in avian leukemia virus E26 v-ets; 4) a phylogenetic analysis of the entire ets family. (1) Low stringency hybridization of S. cerevisiae DNA digested by four different sets of enzymes to a radiolabeled sea urchin ets probe revealed approximately four major bands for each set of enzymes. Three unique bacteriophage lambda clones that hybridize to ets sequences were isolated by screening a S. cerevisiae genomic library under the same conditions. (2) A genomic clone from the sea urchin Lytechinus variegatus was found to be the homolog of the ets family genes, ERG and Fli-1. It contains an open reading frame, of which the 173 amino acid coding region begins at a splice acceptor site. The first 84 of these amino acids are homologous to all ets family genes, while the remainder of the sequence represents a highly-conserved erg-specific domain. (3) The segment of the E26 genome near the termination of the p135gag-myb-ets open reading frame was found to contain an inversion of the chicken ets-1 sequence. The inversion contains at least 41 bp, and may be as large as 46 bp. This results in the replacement of 13 amino acids of chicken ets-1, with 16 amino acids derived from the reverse complement of the normal ets-1 coding strand or read-through into E26 env sequences. The altered carboxy terminal sequences may be responsible for the different oncogenic potential of v- ets, as contrasted to chicken ets-1. (4) A phylogenetic analysis of 32 ets sequences revealed that this family of genes may be divided into 11 subgroups. Analysis of these clusters allows the history of the evolution of the ets gene family to be examined in the context of metazoan radiation. Homologous ets-related genes have been found in three phyla (Chordata, Echinodermata, and Arthropoda). Of the 10 subgroups, 4 have representatives in more than one phyla, implying that several gene duplications occurred prior to the divergence of these phyla over 500 million years ago.