Molecular Phylogeny of OVOL Genes Illustrates a Conserved C2H2 Zinc Finger Domain Coupled by Hypervariable Unstructured Regions

Abstract

OVO-like proteins (OVOL) are members of the zinc finger protein family and serve as transcription factors to regulate gene expression in various differentiation processes. Recent studies have shown that OVOL genes are involved in epithelial development and differentiation in a wide variety of organisms; yet there is a lack of comprehensive studies that describe OVOL proteins from an evolutionary perspective. Using comparative genomic analysis, we traced three different OVOL genes (OVOL1-3) in vertebrates. One gene, OVOL3, was duplicated during a whole-genome-duplication event in fish, but only the copy (OVOL3b) was retained. From early-branching metazoa to humans, we found that a core domain, comprising a tetrad of C2H2 zinc fingers, is conserved. By domain comparison of the OVOL proteins, we found that they evolved in different metazoan lineages by attaching intrinsically-disordered (ID) segments of N/C-terminal extensions of 100 to 1000 amino acids to this conserved core. These ID regions originated independently across different animal lineages giving rise to different types of OVOL genes over the course of metazoan evolution. We illustrated the molecular evolution of metazoan OVOL genes over a period of 700 million years (MY). This study both extends our current understanding of the structure/function relationship of metazoan OVOL genes, and assembles a good platform for further characterization of OVOL genes from diverged organisms.

OVO-like 1 regulates progenitor cell fate in human trophoblast development

“…Intriguingly, OVOL1-deficient mice are viable until birth, and no evident defects in placentation have been reported (20), but OVOL2-deficient mice die by midgestation with severe deficits in the development of the labyrinth placenta, the murine equivalent of the chorionic villi (50). OVOL2 binds to the same DNA-binding site as OVOL1 and can exert functions redundant to those of OVOL1 (46,51,52). Thus, it could be proposed that OVOL2 regulates placentation in mice and rats in a manner similar to the actions of OVOL1 in humans.…”

Conserved role of Ovo in germline development in mouse and Drosophila

“…By contrast, we show here that in Drosophila , maternal Ovo-B activates expression of genes highly enriched in PGCs and conversely suppresses somatic gene expression, thereby contributing to determination of “germness”. The ovo gene family is conserved across animal species, and encodes transcription factors regulating gene expression in various differentiation processes13. In light of the fact that an ovo ortholog is required for PGC formation in mice, we propose that Ovo acts as part of an evolutionarily conserved mechanism regulating the genetic network of germline development.…”

“…Ovo is evolutionarily conserved across a wide range of animals13. In Drosophila, ovo produces three alternate isoforms: Ovo-A and Ovo-B function as a negative and positive transcriptional regulator in the germline during oogenesis, respectively14, whereas Svb is required for epidermal differentiation1516.…”

“…Irrespective of the two modes of germline formation, ovo orthologs are widely conserved among animal species13. For example, three ovo orthologs have been identified in the mouse nuclear genome13.…”

“…For example, three ovo orthologs have been identified in the mouse nuclear genome13. The zinc-finger domains of Ovol1, Ovol2/MOVO , and Ovol3 share 74%, 68%, and 58% amino-acid identity, respectively, with Drosophila ovo 1920.…”