Molecular properties and evolutionary origins of a parvovirus-derived myosin fusion gene in guinea pigs

Abstract

word count: 239 17 Text word count: 3128 18 2 Abstract 19Sequences derived from parvoviruses (family Parvoviridae) are relatively common in 20 animal genomes, but the functional significance of these endogenous parvoviral element (EPV) 21 sequences remains unclear. In this study we use a combination of in silico and molecular 22 biological approaches to investigate a fusion gene encoded by guinea pigs (genus Cavia) that is 23 partially derived from an EPV. This gene, named enRep-Myo9, encodes a predicted polypeptide 24 gene product comprising a partial myosin9 (Myo9)-like gene fused to a 3' truncated, EPV-25 encoded replicase. We first examined the genomic and phylogenetic characteristics of the EPV 26 locus that encodes the viral portions of enRep-Myo9. We show that this locus, named enRep, is 27 specific to guinea pigs and derives from an ancient representative of the parvoviral genus 28 Dependoparvovirus that integrated into the guinea pig germline 22-35 million years ago. Despite 29 these ancient origins, however, the regions of enRep that are incorporated into the coding 30 sequence of the enRep-Myo9 gene are conserved across multiple species in the family Caviidae 31 (guinea pigs and cavies) consistent with purifying selection. Using molecular biological 32 approaches, we further demonstrate that: (i) enRep-Myo9 mRNA is broadly transcribed in guinea 33 pig cells; (ii) the cloned enRep-Myo9 transcript can express a protein of the expected size in 34 guinea pig cells in vitro, and; (iii) the expressed protein localizes to the cytosol. Our findings 35 demonstrate that, consistent with a functional role, the enRep-Myo9 fusion gene is evolutionarily 36 conserved, broadly transcribed, and capable of expressing protein. 37 38 Importance 39DNA from viruses has been 'horizontally transferred' to mammalian genomes during 40 evolution, but the impact of this process on mammalian biology remains poorly understood. The 41 3 findings of our study indicate that in guinea pigs a novel gene has evolved through fusion of host 42 and virus genes. 43 44

Comparative analysis reveals the long-term co-evolutionary history of parvoviruses and vertebrates

“…Our results reveal that mammals acquired EPVs at a much higher frequency than other vertebrate groups (Table 2). In addition to the previously reported dependoparvovirus-derived elements in "whippomorphs" (cetaceans and hippopotamus) [13], lagomorphs, Old World rodents [7], New World rodents [24,26], elephants [25], and macropoids [12] we identified numerous other ancient EPV loci diverse range of animal species (Table S1, Fig 3). Orthologous sets of EPV sequences demonstrating were also identified in passerine birds (order Passeriformes), establishing the ancestral presence of these viruses among ancestral members of clade Neoaves >85 Mya [35].…”

“…Previous studies have shown that some EPV loci express RNA with the potential to encode polypeptide gene products, either as unspliced viral RNA [12,24,25], or as fusion genes comprising RNA sequences derived from both host and viral sources [26]. We examined coding potential in EPVs and identified numerous sequences capable of encoding uninterrupted polypeptide sequences of 300 amino acids (aa) or more, with some ranging up to 722aa (Table S7).…”

“…These observations suggest that expression of Rep protein or mRNA might -in some way -be physiologically relevant. More broadly, incorporation of parvovirus-derived DNA into animal germlines may provide a novel DNA substrate for the evolution of new genes -for example, guinea pigs (Cavia porcellus) encode a predicted polypeptide gene product comprising a partial myosin9-like (M9l) gene fused to a 3' truncated, EPV-encoded replicase [26].…”

An Ancient Lineage of Highly Divergent Parvoviruses Infects both Vertebrate and Invertebrate Hosts

“…Though we did not identify any orthologous ChPV insertions, the EPVs described here show extensive evidence of germline degradation. Through comparison to studies of EPVs in mammals (in which several orthologous EPVs have been described [13,48]), it appears likely that ChPVs have been present in animals for many millions of years. Moreover, as the hexapod EPVs appear to be monophyletic and mirror the evolution of their host species, the age of ChPVs could possibly correlate with the Insecta–Entognatha split, suggesting a minimum age of 400 million years [49].…”