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Contribution of type W human endogenous retroviruses to the human genome: characterization of HERV-W proviral insertions and processed pseudogenes

View Article: PubMed Central - PubMed

ABSTRACT

Background: Human endogenous retroviruses (HERVs) are ancient sequences integrated in the germ line cells and vertically transmitted through the offspring constituting about 8 % of our genome. In time, HERVs accumulated mutations that compromised their coding capacity. A prominent exception is HERV-W locus 7q21.2, producing a functional Env protein (Syncytin-1) coopted for placental syncytiotrophoblast formation. While expression of HERV-W sequences has been investigated for their correlation to disease, an exhaustive description of the group composition and characteristics is still not available and current HERV-W group information derive from studies published a few years ago that, of course, used the rough assemblies of the human genome available at that time. This hampers the comparison and correlation with current human genome assemblies.

Results: In the present work we identified and described in detail the distribution and genetic composition of 213 HERV-W elements. The bioinformatics analysis led to the characterization of several previously unreported features and provided a phylogenetic classification of two main subgroups with different age and structural characteristics. New facts on HERV-W genomic context of insertion and co-localization with sequences putatively involved in disease development are also reported.

Conclusions: The present work is a detailed overview of the HERV-W contribution to the human genome and provides a robust genetic background useful to clarify HERV-W role in pathologies with poorly understood etiology, representing, to our knowledge, the most complete and exhaustive HERV-W dataset up to date.

Electronic supplementary material: The online version of this article (doi:10.1186/s12977-016-0301-x) contains supplementary material, which is available to authorized users.

No MeSH data available.


Insertion and deletions of the 59 proviral sequences >2.5 Kb with respect to LTR17-HERV17-LTR17 reference
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Fig2: Insertion and deletions of the 59 proviral sequences >2.5 Kb with respect to LTR17-HERV17-LTR17 reference

Mentions: Secondly, in order to define the group structural characteristics, the 213 HERV-W elements were further analyzed in great detail by annotating all insertions/deletions with respect to the consensus LTR17-HERV17-LTR17, as schematically represented for the 59 proviruses with minimum length of 2.5 Kb in Fig. 2. In comparison to the consensus, in all types of sequences some recurrent deletions clearly affect viral genes, with the loss of some big viral portions: (1) nucleotides 2780–3209 in gag gene (45 % of the sequences), (2) nucleotides 4513–6184 and 6797–7692 (IN portion) in pol gene (28 and 84 % of the sequences, respectively), and (3) nucleotides 7928–9114 in the env gene (85 % of the sequences), with the exception of a small region of about 30 nucleotides at position 8289–8318 that is frequently present despite the flanking deletions. Interestingly, the recurrent loss of pol and env genes, deleted in the C-terminal IN portion and retaining only the TM intracytoplasmic tail, respectively, possibly suggests a selective removal of regions that were no longer needed in the absence of an active infective transmission.Fig. 2


Contribution of type W human endogenous retroviruses to the human genome: characterization of HERV-W proviral insertions and processed pseudogenes
Insertion and deletions of the 59 proviral sequences >2.5 Kb with respect to LTR17-HERV17-LTR17 reference
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5016936&req=5

Fig2: Insertion and deletions of the 59 proviral sequences >2.5 Kb with respect to LTR17-HERV17-LTR17 reference
Mentions: Secondly, in order to define the group structural characteristics, the 213 HERV-W elements were further analyzed in great detail by annotating all insertions/deletions with respect to the consensus LTR17-HERV17-LTR17, as schematically represented for the 59 proviruses with minimum length of 2.5 Kb in Fig. 2. In comparison to the consensus, in all types of sequences some recurrent deletions clearly affect viral genes, with the loss of some big viral portions: (1) nucleotides 2780–3209 in gag gene (45 % of the sequences), (2) nucleotides 4513–6184 and 6797–7692 (IN portion) in pol gene (28 and 84 % of the sequences, respectively), and (3) nucleotides 7928–9114 in the env gene (85 % of the sequences), with the exception of a small region of about 30 nucleotides at position 8289–8318 that is frequently present despite the flanking deletions. Interestingly, the recurrent loss of pol and env genes, deleted in the C-terminal IN portion and retaining only the TM intracytoplasmic tail, respectively, possibly suggests a selective removal of regions that were no longer needed in the absence of an active infective transmission.Fig. 2

View Article: PubMed Central - PubMed

ABSTRACT

Background: Human endogenous retroviruses (HERVs) are ancient sequences integrated in the germ line cells and vertically transmitted through the offspring constituting about 8 % of our genome. In time, HERVs accumulated mutations that compromised their coding capacity. A prominent exception is HERV-W locus 7q21.2, producing a functional Env protein (Syncytin-1) coopted for placental syncytiotrophoblast formation. While expression of HERV-W sequences has been investigated for their correlation to disease, an exhaustive description of the group composition and characteristics is still not available and current HERV-W group information derive from studies published a few years ago that, of course, used the rough assemblies of the human genome available at that time. This hampers the comparison and correlation with current human genome assemblies.

Results: In the present work we identified and described in detail the distribution and genetic composition of 213 HERV-W elements. The bioinformatics analysis led to the characterization of several previously unreported features and provided a phylogenetic classification of two main subgroups with different age and structural characteristics. New facts on HERV-W genomic context of insertion and co-localization with sequences putatively involved in disease development are also reported.

Conclusions: The present work is a detailed overview of the HERV-W contribution to the human genome and provides a robust genetic background useful to clarify HERV-W role in pathologies with poorly understood etiology, representing, to our knowledge, the most complete and exhaustive HERV-W dataset up to date.

Electronic supplementary material: The online version of this article (doi:10.1186/s12977-016-0301-x) contains supplementary material, which is available to authorized users.

No MeSH data available.