Extensive retroviral diversity in shark
© Han; licensee BioMed Central. 2015
Received: 12 December 2014
Accepted: 23 March 2015
Published: 28 April 2015
Retroviruses infect a wide range of vertebrates. However, little is known about the diversity of retroviruses in basal vertebrates. Endogenous retrovirus (ERV) provides a valuable resource to study the ecology and evolution of retrovirus.
I performed a genome-scale screening for ERVs in the elephant shark (Callorhinchus milii) and identified three complete or nearly complete ERVs and many short ERV fragments. I designate these retroviral elements “C. milli ERVs” (CmiERVs). Phylogenetic analysis shows that the CmiERVs form three distinct lineages. The genome invasions by these retroviruses are estimated to take place more than 50 million years ago.
My results reveal the extensive retroviral diversity in the elephant shark. Diverse retroviruses appear to have been associated with cartilaginous fishes for millions of years. These findings have important implications in understanding the diversity and evolution of retroviruses.
Retroviruses infect a wide range of vertebrates and cause many notorious diseases, such as AIDS and cancers. However, much remains unknown about the diversity of retroviruses in basal vertebrate species. In particular, only several retroviruses have been identified in fishes, including Snakehead retrovirus, walleye dermal sarcoma virus, walleye epidermal hyperplasia virus, and Atlantic salmon swim bladder sarcoma virus [1-4]. Retrovirus employs a unique replication strategy, which requires reverse transcription of its RNA genome into DNA and integration of viral DNA into the host chromosomes. Occasionally, retroviruses infect germ line cells, and the resulting integrated retrovirus, known as endogenous retrovirus (ERV), becomes vertically inherited as a host genomic locus. Over time, some retroviral insertions are fixed in the host population. ERVs provide important insights into the ecology and evolutionary history of retroviruses.
Cartilaginous fishes (Chondrichthyes) are the most basal class of vertebrates from which retrovirus has been reported . Here, I analyzed the recently available genome sequence of the elephant shark (Callorhinchus milii), a high-quality genome assembly covering approximately 94% of the C. milii genome, for retroviral insertions . The tBLASTn algorithm with various representative retroviral Pol protein sequences was employed to screen the elephant shark genome for candidate ERV sequences. To distinguish ERVs from other LTR-retrotransposons, I used a strict criterion: only the retroviral Pol protein homolog sequence with a downstream Env protein homolog is defined as an ERV element. After initial identification of ERVs, the BLASTn algorithm was used to identify short ERV fragments. My genome-scale screening procedure identified three complete or nearly complete ERV insertions (within the C. milii genome scaffolds 2, 324, and 2324, respectively; Additional file 1: Dataset 1) and many short ERV fragments in the elephant shark genome. I designate these retroviral elements “C. milli ERVs” (CmiERVs).
Genomic position and invasion time of two complete CmiERV insertions
5′- and 3′LTR divergence
Scaffold 2: 5,443,211-5,452,770
Scaffold 324: 74,676-84,761
Previously, a single ERV sequence was identified in the lemon shark (Negaprion brevirostris), which is closely related to human ERV; this ERV was thought to have a cross-transmission origin . However, I find that CmiERVs cluster together with retroviruses of fish origin. The phylogenetic pattern is compatible with the hypothesis of an ancient marine origin of retroviruses . Chondrichthyes are the most basal class of vertebrates from which retrovirus has been identified; no retrovirus is identified in earlier-diverging vertebrate lineages, the lampreys (Cephalaspidomorphi) and the hagfish (Myxini) . It follows that these CmiERV elements are likely to represent “primitive” retroviruses. However, the possibility that these elephant shark retroviruses originated from cross-transmission from other fishes cannot be formally excluded.
To date, only a limited number of exogenous/endogenous retroviruses have been identified in fishes [1-5,14]. My results reveal the unexpectedly extensive retroviral diversity of the elephant shark. The initial candidate ERVs were identified based on a strict criterion – whether there is a downstream Env protein homolog following the Pol protein homolog. This approach is conservative, given that the retroviral Env protein evolves rapidly and its similarity to other retroviral Env proteins will erode over a long time. On the other hand, the ERVs identified using this approach are authentic retroviruses. It is likely that there are additional ERV insertions that were not detected. Also, it should be noted that only a small proportion of retroviruses could leave endogenous copies in their host genomes . Therefore, I believe the actual diversity of retroviruses is more extensive in the elephant shark. Further analysis of ERV in basal vertebrates would improve our understanding of the diversity and evolution of retroviruses.
This research was supported by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions. I thank Chunyang Wang for helping prepare Figure 1.
- Hart D, Frerichs GN, Rambaut A, Onions DE. Complete nucleotide sequence and transcriptional analysis of snakehead fish retrovirus. J Virol. 1996;70:3606–16.PubMed CentralPubMedGoogle Scholar
- LaPierre LA, Holzschu DL, Bowser PR, Casey JW. Sequence and transcriptional analyses of the fish retroviruses walleye epidermal hyperplasia virus types 1 and 2: evidence for a gene duplication. J Virol. 1999;73:9393–403.PubMed CentralPubMedGoogle Scholar
- Holzschu DL, Martineau D, Fodor SK, Vogt VM, Bowser PR, Casey JW. Nucleotide sequence and protein analysis of a complex piscine retrovirus, walleye dermal sarcoma virus. J Virol. 1995;69:5320–31.PubMed CentralPubMedGoogle Scholar
- Paul TA, Quackenbush SL, Sutton C, Casey RN, Bowser PR, Casey JW. Identification and characterization of an exogenous retrovirus from atlantic salmon swim bladder sarcomas. J Virol. 2006;80:2941–8.View ArticlePubMed CentralPubMedGoogle Scholar
- Herniou E, Martin J, Miller K, Cook J, Wilkinson M, Tristem M. Retroviral diversity and distribution in vertebrates. J Virol. 1998;72:5955–66.PubMed CentralPubMedGoogle Scholar
- Venkatesh B, Lee AP, Ravi V, Maurya AK, Lian MM, Swann JB, et al. Elephant shark genome provides unique insights into gnathostome evolution. Nature. 2014;505:174–9.View ArticlePubMed CentralPubMedGoogle Scholar
- Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004;32:1792–7.View ArticlePubMed CentralPubMedGoogle Scholar
- Talavera G, Castresana J. Improvement of phylogenies after removing divergent and ambiguously aligned blocks from protein sequence alignments. Syst Biol. 2007;56:564–77.View ArticlePubMedGoogle Scholar
- Ronquist F, Huelsenbeck JP. Mrbayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics. 2003;19:1572–4.View ArticlePubMedGoogle Scholar
- Johnson WE, Coffin JM. Constructing primate phylogenies from ancient retrovirus sequences. Proc Natl Acad Sci USA. 1999;96:10254–60.View ArticlePubMed CentralPubMedGoogle Scholar
- Kimura M. A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol. 1980;16:111–20.View ArticlePubMedGoogle Scholar
- Martin AP. Substitution rates of organelle and nuclear genes in sharks: implicating metabolic rate (again). Mol Biol Evol. 1999;16:996–1002.View ArticlePubMedGoogle Scholar
- Kumar S, Subramanian S. Mutation rates in mammalian genomes. Proc Proc Natl Acad Sci USA. 2002;99:803–8.View ArticleGoogle Scholar
- Han GZ, Worobey M. A primitive endogenous lentivirus in a colugo: insights into the early evolution of lentiviruses. Mol Biol Evol. 2015;32:211–5.View ArticlePubMedGoogle Scholar
- Han GZ, Worobey M. An endogenous foamy-like viral element in the coelacanth genome. PLoS Pathog. 2012;8:e1002790.View ArticlePubMed CentralPubMedGoogle Scholar
- Emerman M, Malik HS. Paleovirology–modern consequences of ancient viruses. PLoS Biol. 2010;8:e1000301.View ArticlePubMed CentralPubMedGoogle Scholar
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.