Genomic Instability and the Evolution of the Antarctic Notothenioid Fishes

Northeastern University, Boston MA

Investigators

Abstract

The ancestral Notothenioid fish stock of Antarctica probably arose as a sluggish, bottom-dwelling species that evolved some 40-60 million years ago in the then temperate shelf waters of the Antarctic continent. The grounding of the ice sheet on the continental shelf and changing trophic conditions may have eliminated the taxonomically diverse late Eocene fauna and initiated the rapid diversification of the Notothenioids. On the High Antarctic shelf, Notothenioids today dominate the fish fauna and are recognized as one of the few examples of a species flock of marine fishes. Recent work conducted by this investigator and others suggests strongly that evolutionary change at the level of the genome permeates the Notothenioids and perhaps has been a major driver of the rapid diversification of this suborder of bony fishes. One striking example is the loss by the icefishes (Channichthyidae) of the ability to produce functional erythrocytes and hemoglobin. This natural "knockout" of the erythroid lineage makes the icefish taxon a unique genetic resource for analyzing the signaling pathways and transcriptional machinery involved in erythroid determination and differentiation. The hemoglobin-null and erythrocyte-null phenotypes appear to have been caused, at least in part, by genomic rearrangements and/or deletions mediated by repetitive elements and retrotransposons. One objective of this proposal will be to evaluate the role of genome instability in the evolution of the hematopoietic program of the icefishes. Using fluorescence in situ hybridization-based cytogenetics and bacterial artificial chromosome (BAC) libraries, erythropoietic gene loci will be mapped physically to the genomes of two notothenioids, the red-blooded rockcod Notothenia coriiceps and the white-blooded icefish Chaenocephalus aceratus, to determine the patterns of gene retention, inactivation, and/or loss that cause the erythrocyte-null condition. A second objective will be to exploit the absence of erythrocytes in icefishes to discover novel genes involved in the erythropoietic genetic program by use of new comparative genomic technologies. A third objective will be to determine the functions of newly discovered erythroid genes and their encoded proteins by functional analysis of zebrafish orthologs in zebrafish embryos. In summary, this research will evaluate the evolutionary mechanisms that generated the novel erythropoietic phenotype of the Antarctic icefishes and will exploit this novel taxon to conduct an unbiased, genome-wide scan for genes involved in red cell formation. The broader impacts include graduate student training in genomic molecular biology, including the bioinformatic strategies necessary to mine the data set for the potential functions of novel erythroid genes, and the use of a model system, the zebrafish, to test the hypothetical functions of these genes. A Web-hosted database will be created so that other laboratories can make use of the genome mapping data generated by this research project and lay audiences can learn about the uses of genomics for solving important questions in polar biology. In addition, the discovery of novel genes that participate in hematopoiesis may contribute important targets for the development by the biotechnology industry of therapeutics to treat anemias, leukemias, and other blood diseases.