Genome-Wide Characterization of Zebrafish Endogenous Retroviruses Reveals Unexpected Diversity in Genetic Organizations and Functional Potentials.

Endogenous retroviruses (ERVs) occupy a substantial fraction of mammalian genomes. However, whether ERVs extensively exist in ancient vertebrates remains unexplored. Here, we performed a genome-wide characterization of ERVs in a zebrafish (Danio rerio) model. Approximately 3,315 ERV-like elements (ERVs) were identified as Gypsy, Copia, Bel, and class I-III groups. ERVs accounted for approximately 2.3% of zebrafish genome and were distributed in all 25 chromosomes, with a remarkable bias on chromosome 4. Gypsy and class I are the two most abundant groups with earlier insertion times. The vast majority of the ERVs have varied structural defects. A total of 509 and 71 genes with coding potentials were detected. The -coding elements were well-characterized and classified into four subgroups. A ERV-E4.8.43-DanRer element shows high similarity with HERV9NC-int in humans and analogous sequences were detected in species spanning from fish to mammals. RNA-seq data showed that hundreds of ERVs were expressed in embryos and tissues under physiological conditions, and most of them exhibited stage and tissue specificity. Additionally, 421 ERVs showed strong responsiveness to virus infection. A unique group of ERVs with immune-relevant genes, such as , , and , instead of intrinsic viral genes were identified. These ERVs are regulated by transcriptional factors binding at the long terminal repeats. This study provided a survey of the composition, phylogeny, and potential functions of ERVs in a fish model, which benefits the understanding of the evolutionary history of ERVs from fish to mammals. Endogenous retroviruses (ERVs) are relics of past infection that constitute up to 8% of the human genome. Understanding the genetic evolution of the ERV family and the interplay of ERVs and encoded RNAs and proteins with host function has become a new frontier in biology. Fish, as the most primitive vertebrate host for retroviruses, is an indispensable integral part for such investigations. In the present study, we report the genome-wide characterization of ERVs in zebrafish, an attractive model organism of ancient vertebrates from multiple perspectives, including composition, genomic organization, chromosome distribution, classification, phylogeny, insertion time, characterization of and genes, and expression profiles in embryos and tissues. The result helps uncover the evolutionarily conserved and fish-specific ERVs, as well as the immune-relevant ERVs in response to virus infection. This study demonstrates the previously unrecognized abundance, diversification, and extensive activity of ERVs at the early stage of ERV evolution.