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.

The clustering of the HERV-K 5′ and 3′ LTR sequences of each insertion suggests that gene conversion is rare in the HERV-K family. Each HERV is indicated by its name (K106 for HERV-K106). HERV taxa that may have undergone gene conversion are indicated in red. HERV-K115 5′LTR clusters with HERV-K109 suggesting a gene conversion occurred between these two HERV-K members. HERV-K10, HERV-K HML2HOM, and HERV-K110 are sometimes referred to as HERV-K107, HERV-K108, and HERV-K18, respectively. HERV-K110 was used to root the phylogeny because it is present in both Humans and Gorillas [16].

Haplotypes and haplotype frequencies of HERV K113 and K106 from individuals in the same sample set are shown. Haplotypes and haplotype frequencies of K113 were obtained from our previous study [25]. Higher minor haplotype frequencies (MHFs) were observed for K113 (18%, 9%, 9%) compared to K106 (8%, 4%, 3%) even though the numbers of K113 LTRs sequenced was much smaller than that compared to K106. Higher K113 MHFs in a subset of our samples compared to that of K106 suggests that K106 integrated into the human genome much later than K106 such that MHFs of K106 have not had enough time to reach higher frequencies in global populations. This serves as an additional evidence for recent insertion integration time of HERV-K106.