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Human endogenous retrovirus K106 (HERV-K106) was infectious after the emergence of anatomically modern humans.

Jha AR, Nixon DF, Rosenberg MG, Martin JN, Deeks SG, Hudson RR, Garrison KE, Pillai SK - PLoS ONE (2011)

Bottom Line: However, recent data suggest that HERV-K113 is at least 800,000 years old, and HERV-K115 even older.A systematic study of HERV-K HML2 members to identify HERVs that may have infected the human genome in the more recent evolutionary past is lacking.Coalescent analysis of HERV-K106 3' LTR sequences representing 51 ethnically diverse individuals suggests that HERV-K106 integrated into the human germ line approximately 150,000 years ago, after the emergence of anatomically modern humans.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America.

ABSTRACT
HERV-K113 and HERV-K115 have been considered to be among the youngest HERVs because they are the only known full-length proviruses that are insertionally polymorphic and maintain the open reading frames of their coding genes. However, recent data suggest that HERV-K113 is at least 800,000 years old, and HERV-K115 even older. A systematic study of HERV-K HML2 members to identify HERVs that may have infected the human genome in the more recent evolutionary past is lacking. Therefore, we sought to determine how recently HERVs were exogenous and infectious by examining sequence variation in the long terminal repeat (LTR) regions of all full-length HERV-K loci. We used the traditional method of inter-LTR comparison to analyze all full length HERV-Ks and determined that two insertions, HERV-K106 and HERV-K116 have no differences between their 5' and 3' LTR sequences, suggesting that these insertions were endogenized in the recent evolutionary past. Among these insertions with no sequence differences between their LTR regions, HERV-K106 had the most intact viral sequence structure. Coalescent analysis of HERV-K106 3' LTR sequences representing 51 ethnically diverse individuals suggests that HERV-K106 integrated into the human germ line approximately 150,000 years ago, after the emergence of anatomically modern humans.

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Genome organization and haplotypes of HERV-K106.Figure 2A: Genomic characterization of HERV-K106 demonstrating the two LTRs, gag, pol, and env genes. The HERV-K106 genome was annotated with the aid of the HERV-K consensus sequence (HERV-KCON) [23], two HERV-K HML2 members that have somewhat functional gag (HERV-K101 and HERV-K109) [43], and insertionally polymorphic HERV-K113 that has intact ORF [17]. Known functional elements within the HERV-K106 LTR are shown in colored boxes. All SNP positions in the coding genes are counted from the beginning of gag ORF. Five nonsynonymous SNPs shown in gag region are HERV-K106 specific. These SNPs do not include I516M mutation which singlehandedly eliminates functionality of HERV-K113 gag [43] warranting the future investigation of functionality of K106 gag. Although K106 lacks this vital SNP it harbors one base deletion at position 1977 which causes a frameshift near the end of the gag gene. Whether this frameshift causes gag to be dysfunctional is unknown. The HERV-K106 polymerase gene (pol) that includes reverse transcriptase is distinct from the other HERV-K family members used in our sequence comparison. In addition to the SNP shown, it harbors a 5 bp deletion from 4849–4853 bp that results in a frameshift mutation. The large 292 base deletion beginning at 5392 bp of pol extending into the env gene is the signature of type-I HERV-K [16]. In addition to the 292 bp deletion, HERV-K106 env gene has a premature stop codon. (<$>\raster(70%)="rg1"<$>) indicate stop codons in HERV-K106 genome. Figure 2B: SNPs and surrounding bases in 3′LTR of HERV-K106 demonstrating four haplotypes. Each haplotype is listed on the left, each SNP is represented in red and the position containing the SNP is highlighted in yellow.
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pone-0020234-g002: Genome organization and haplotypes of HERV-K106.Figure 2A: Genomic characterization of HERV-K106 demonstrating the two LTRs, gag, pol, and env genes. The HERV-K106 genome was annotated with the aid of the HERV-K consensus sequence (HERV-KCON) [23], two HERV-K HML2 members that have somewhat functional gag (HERV-K101 and HERV-K109) [43], and insertionally polymorphic HERV-K113 that has intact ORF [17]. Known functional elements within the HERV-K106 LTR are shown in colored boxes. All SNP positions in the coding genes are counted from the beginning of gag ORF. Five nonsynonymous SNPs shown in gag region are HERV-K106 specific. These SNPs do not include I516M mutation which singlehandedly eliminates functionality of HERV-K113 gag [43] warranting the future investigation of functionality of K106 gag. Although K106 lacks this vital SNP it harbors one base deletion at position 1977 which causes a frameshift near the end of the gag gene. Whether this frameshift causes gag to be dysfunctional is unknown. The HERV-K106 polymerase gene (pol) that includes reverse transcriptase is distinct from the other HERV-K family members used in our sequence comparison. In addition to the SNP shown, it harbors a 5 bp deletion from 4849–4853 bp that results in a frameshift mutation. The large 292 base deletion beginning at 5392 bp of pol extending into the env gene is the signature of type-I HERV-K [16]. In addition to the 292 bp deletion, HERV-K106 env gene has a premature stop codon. (<$>\raster(70%)="rg1"<$>) indicate stop codons in HERV-K106 genome. Figure 2B: SNPs and surrounding bases in 3′LTR of HERV-K106 demonstrating four haplotypes. Each haplotype is listed on the left, each SNP is represented in red and the position containing the SNP is highlighted in yellow.

Mentions: We used Multalin [22] to align HERV-K113, K115, K106, and K116 with experimentally reconstituted infectious HERVs KCON [23] and Phoenix [24] that are based on artificial consensus sequences of full-length human-specific HERV-K (HML-2) insertions. We observed that while all four HERV insertions (K113, K115, K106, and K116) exhibited similarities to the reconstituted viruses, all four contained mutations that were unique to each insertion (Figure S1). We observed that both HERV-K106 and HERV-K116 are members of the type I HERV-K family as evidenced by the presence of a 292 bp ‘deletion’ in env which is the signature of all type I HERV members. The presence of this 292 bp env deletion in multiple HERV-K type I members suggests that this deletion may have been present in the infectious ancestral precursors of these viruses and probably does not render a HERV insertion dysfunctional on its own. However, HERV-K116 also has a 2846 bp deletion in its pol sequence [16]. In contrast, HERV-K106 exhibits relatively intact retroviral genome architecture (Figure 2A). Thus, these data suggest that HERV-K106 is the youngest endogenous retrovirus that survives largely intact in the human genome.


Human endogenous retrovirus K106 (HERV-K106) was infectious after the emergence of anatomically modern humans.

Jha AR, Nixon DF, Rosenberg MG, Martin JN, Deeks SG, Hudson RR, Garrison KE, Pillai SK - PLoS ONE (2011)

Genome organization and haplotypes of HERV-K106.Figure 2A: Genomic characterization of HERV-K106 demonstrating the two LTRs, gag, pol, and env genes. The HERV-K106 genome was annotated with the aid of the HERV-K consensus sequence (HERV-KCON) [23], two HERV-K HML2 members that have somewhat functional gag (HERV-K101 and HERV-K109) [43], and insertionally polymorphic HERV-K113 that has intact ORF [17]. Known functional elements within the HERV-K106 LTR are shown in colored boxes. All SNP positions in the coding genes are counted from the beginning of gag ORF. Five nonsynonymous SNPs shown in gag region are HERV-K106 specific. These SNPs do not include I516M mutation which singlehandedly eliminates functionality of HERV-K113 gag [43] warranting the future investigation of functionality of K106 gag. Although K106 lacks this vital SNP it harbors one base deletion at position 1977 which causes a frameshift near the end of the gag gene. Whether this frameshift causes gag to be dysfunctional is unknown. The HERV-K106 polymerase gene (pol) that includes reverse transcriptase is distinct from the other HERV-K family members used in our sequence comparison. In addition to the SNP shown, it harbors a 5 bp deletion from 4849–4853 bp that results in a frameshift mutation. The large 292 base deletion beginning at 5392 bp of pol extending into the env gene is the signature of type-I HERV-K [16]. In addition to the 292 bp deletion, HERV-K106 env gene has a premature stop codon. (<$>\raster(70%)="rg1"<$>) indicate stop codons in HERV-K106 genome. Figure 2B: SNPs and surrounding bases in 3′LTR of HERV-K106 demonstrating four haplotypes. Each haplotype is listed on the left, each SNP is represented in red and the position containing the SNP is highlighted in yellow.
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Related In: Results  -  Collection

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pone-0020234-g002: Genome organization and haplotypes of HERV-K106.Figure 2A: Genomic characterization of HERV-K106 demonstrating the two LTRs, gag, pol, and env genes. The HERV-K106 genome was annotated with the aid of the HERV-K consensus sequence (HERV-KCON) [23], two HERV-K HML2 members that have somewhat functional gag (HERV-K101 and HERV-K109) [43], and insertionally polymorphic HERV-K113 that has intact ORF [17]. Known functional elements within the HERV-K106 LTR are shown in colored boxes. All SNP positions in the coding genes are counted from the beginning of gag ORF. Five nonsynonymous SNPs shown in gag region are HERV-K106 specific. These SNPs do not include I516M mutation which singlehandedly eliminates functionality of HERV-K113 gag [43] warranting the future investigation of functionality of K106 gag. Although K106 lacks this vital SNP it harbors one base deletion at position 1977 which causes a frameshift near the end of the gag gene. Whether this frameshift causes gag to be dysfunctional is unknown. The HERV-K106 polymerase gene (pol) that includes reverse transcriptase is distinct from the other HERV-K family members used in our sequence comparison. In addition to the SNP shown, it harbors a 5 bp deletion from 4849–4853 bp that results in a frameshift mutation. The large 292 base deletion beginning at 5392 bp of pol extending into the env gene is the signature of type-I HERV-K [16]. In addition to the 292 bp deletion, HERV-K106 env gene has a premature stop codon. (<$>\raster(70%)="rg1"<$>) indicate stop codons in HERV-K106 genome. Figure 2B: SNPs and surrounding bases in 3′LTR of HERV-K106 demonstrating four haplotypes. Each haplotype is listed on the left, each SNP is represented in red and the position containing the SNP is highlighted in yellow.
Mentions: We used Multalin [22] to align HERV-K113, K115, K106, and K116 with experimentally reconstituted infectious HERVs KCON [23] and Phoenix [24] that are based on artificial consensus sequences of full-length human-specific HERV-K (HML-2) insertions. We observed that while all four HERV insertions (K113, K115, K106, and K116) exhibited similarities to the reconstituted viruses, all four contained mutations that were unique to each insertion (Figure S1). We observed that both HERV-K106 and HERV-K116 are members of the type I HERV-K family as evidenced by the presence of a 292 bp ‘deletion’ in env which is the signature of all type I HERV members. The presence of this 292 bp env deletion in multiple HERV-K type I members suggests that this deletion may have been present in the infectious ancestral precursors of these viruses and probably does not render a HERV insertion dysfunctional on its own. However, HERV-K116 also has a 2846 bp deletion in its pol sequence [16]. In contrast, HERV-K106 exhibits relatively intact retroviral genome architecture (Figure 2A). Thus, these data suggest that HERV-K106 is the youngest endogenous retrovirus that survives largely intact in the human genome.

Bottom Line: However, recent data suggest that HERV-K113 is at least 800,000 years old, and HERV-K115 even older.A systematic study of HERV-K HML2 members to identify HERVs that may have infected the human genome in the more recent evolutionary past is lacking.Coalescent analysis of HERV-K106 3' LTR sequences representing 51 ethnically diverse individuals suggests that HERV-K106 integrated into the human germ line approximately 150,000 years ago, after the emergence of anatomically modern humans.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America.

ABSTRACT
HERV-K113 and HERV-K115 have been considered to be among the youngest HERVs because they are the only known full-length proviruses that are insertionally polymorphic and maintain the open reading frames of their coding genes. However, recent data suggest that HERV-K113 is at least 800,000 years old, and HERV-K115 even older. A systematic study of HERV-K HML2 members to identify HERVs that may have infected the human genome in the more recent evolutionary past is lacking. Therefore, we sought to determine how recently HERVs were exogenous and infectious by examining sequence variation in the long terminal repeat (LTR) regions of all full-length HERV-K loci. We used the traditional method of inter-LTR comparison to analyze all full length HERV-Ks and determined that two insertions, HERV-K106 and HERV-K116 have no differences between their 5' and 3' LTR sequences, suggesting that these insertions were endogenized in the recent evolutionary past. Among these insertions with no sequence differences between their LTR regions, HERV-K106 had the most intact viral sequence structure. Coalescent analysis of HERV-K106 3' LTR sequences representing 51 ethnically diverse individuals suggests that HERV-K106 integrated into the human germ line approximately 150,000 years ago, after the emergence of anatomically modern humans.

Show MeSH
Related in: MedlinePlus