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Flavivirus GLUE EVE Project Background

Robert J. Gifford edited this page Nov 24, 2024 · 20 revisions

Endogenous Flaviviral Elements

Timeline of flavivirus evolution

A proposed timeline of flavivirus evolution: A model for long-term evolution of flavivirids, taken from Bamford et al, 2022. The time-scaled tree shows the phylogenetic relationships of flavivirids calibrated using information obtained from analysis of EVEs, co-phyletic analysis, and the fossil record of haematophagous arthropods. Symbols on the phylogenies indicate types of calibration as shown in the key. Codivergence type A = codivergence supported by co-phylogeny. Codivergence type B = potential codivergence-based calibrations without supporting evidence. Vertical lines to right of the tree show taxonomic groups. MYA=million years ago.

Endogenous viral elements (EVEs) are virus-derived sequences that occur in the germline genomes of cellular organisms. EVEs derived from a diverse range of virus families have been identified, including flavivirids. These ‘endogenous flavivirids’ (EFVs) can originate from RNA viruses when infection of germline cells leads to virus-derived complementary deoxyribonucleic acid (cDNA) being incorporated into chromosomal DNA so that integrated viral genes are inherited as host alleles. Sometimes, these sequences persist in the gene pool over many generations until they are genetically fixed (i.e. reach a frequency of 100 per cent in the species gene pool).

Currently, the distribution and diversity of EFVs remains incompletely characterized. Progress in characterising and analysing these elements has been hampered by the challenges encountered attempting to analyse their fragmentary and degenerated sequences. Flavivirus-GLUE-EVE aims to address these issues.


Relevance to Flavivirus Research

  • Evolution: EVEs provide insights into the long-term evolutionary history of virus groups, which greatly influences how we understand their biology.

  • Genomics: Some EFVs may have, or have had, functional roles as host alleles.

  • Virus discovery: When new flavivirus species are identified, inclusion of EVEs in phylogenetic analyses can provide useful contextual information. Addionally, the EFV sequences collated here can be used to exclude any potential 'false positive' hits that arise in metagenomics-driven virus discovery efforts (i.e. sequences that seem to represent new flaviviruses but in fact derive from genomic DNA).

  • EVE discovery: Using the EFV sequences provided here as 'probes' for in silico genome screening may enable the detection of novel EFV elements.


What the Flavivirus-GLUE EVE Extension Offers:

The Flavivirus-GLUE-EVE project is designed to provide a comprehensive and accessible resource for the analysis of EFV sequences. Key features include:

  • GLUE Framework Integration: As part of the Flavivirus-GLUE project, the information contained in this repository can be accessed via GLUE's command layer, minimizing the need for labor-intensive pre-processing and enabling streamlined workflows.

  • Standardized Nomenclature: A consistent naming system for EFV loci to ensure clarity and interoperability across studies.

  • Genomic Mapping: A detailed map showing the precise genomic locations of all known EFV loci in published whole genome sequence assemblies, aiding in comparative genomic studies.

  • Paleovirus Consensus Genomes: Annotated consensus genomes for the ancient flaviviruses that gave rise to the EFVs, offering a reconstructed view of these viral ancestors.

  • Sequence Alignments: Pre-aligned EFV sequences and modern flavivirus genomes to facilitate comparative analysis.

  • Evolutionary Phylogenies: Phylogenetic trees illustrating the evolutionary relationships between EFV sequences and extant flaviviruses, shedding light on the long-term co-evolution of these viruses with their hosts.