Joo-Mi Yi

Molecular Evolution of the Periphilin Gene in Relation to Human Endogenous Retrovirus M Element

HERV-M (human endogenous retrovirus M), related to the super family of HERV-K, has a methionine (M) tRNA primer-binding site, and is located within the periphilin gene on human chromosome 12q12. HERV-M has been integrated into the periphilin gene as the truncated form, 5′LTR-gag-pol-3′LTR. Polymerase chain reaction (PCR) and reverse transcription-polymerase chain reaction (RT-PCR) approaches were conducted to investigate its evolutionary origins. Interestingly, the insertion of retroelements in a common ancestor genome can make different transcript variants in different species. In the case of the periphilin gene, human (10 variants) and mouse (2 variants) lineages show different transcript variants. Insertion of HERV-M (variant 1-3) could affect the protein-coding region. Also, Alusq/x (variant 4-9) and L1ME4a (mammalian-wide subfamilies of LINE-1) (variant 10) in humans and SINE (short interspersed repetitive element) and RLTR15 (the mouse putative long terminal repeat) (variant 2) in mice could be driving forces in transcript diversification of the periphilin gene during mammalian evolution. The HERV-M derived transcripts (variant 1-3) were expressed in different human tissues, whereas they were not detected in crab-eating monkey and squirrel monkey tissues by RT-PCR amplification. Taken together, HERV-M seems to have been integrated into our common ancestor genome after the divergence of simians and prosimians, and then was actively expressed during hominoid evolution.

Expression of Human Endogenous Retrovirus env Genes in the Blood of Breast Cancer Patients

Human endogenous retroviruses (HERV) env proteins have been recently reported to be significantly up-regulated in certain cancers. Specifically, mRNA and protein levels of HERV-K (HML-2) are up-regulated in the blood plasma or serum of breast cancer patients. Here, we collected blood samples of 49 breast cancer patients and analyzed mRNA expressions of various HERVs env genes including HERV-R, HERV-H, HERV-K, and HERV-P by real-time PCR. The expression of env genes were significantly increased in the blood of primary breast cancer patients but were decreased in patients undergoing chemotherapy to a similar level with benign patients. When we compared the group currently undergoing chemotherapy and those patients undergoing chemotherapy simultaneously with radiotherapy, HERVs env genes were reduced more in the chemotherapy only group, suggesting that chemotherapy is more effective in reducing HERV env gene expression than is radiotherapy. Among chemotherapy groups, HERV env gene expression was the lowest in the taxotere- or taxol-treated group, suggesting that taxotere and taxol can reduce HERVs env expression. These data suggest the potential to use HERVs env genes as a diagnosis marker for primary breast cancer, and further studies are needed to identify the mechanism and physiological significance of the reduction of HERV env gene expression during chemotherapy.

Molecular evolution of the HERV-E family in primates

Summary.More than 50 copies of HERV-E family elements have been estimated to exist in the human genome. Here we examined the recent evolutionary history of the HERV-E family by a PCR approach using genomic DNA from hominoid primates and a human monochromosomal panel. From the HERV-E family, 25 and 68 env fragments, were identified and analyzed from hominoid primates and human chromosomes 1, 2, 3, 4, 6, 7, 8, 10, 11, 12, 13, 14, 15, 16, 17, 19, X, and Y, respectively. They showed 76.7–99.6% sequence similarity to that of HERV-E (accession no. M10976). Phylogenetic analysis of HERV-E env family distinctively divided into two groups (groups I and II) that each contained three subgroups. Divergence times of the two groups were estimated as 10.7 MYr for group I and 41.3 MYr for group II using an average evolutionary rate of 0.3% per MYr. These data are consistent with that of PCR analysis, which showed a band of the HERV-E family in the genomes of the hominoids, Old World monkeys, and New World monkeys. Therefore, the HERV-E family may have integrated into the primate genome after prosimians and New World monkeys diverged. Then they proliferated extensively in the genome of humans and great apes during primate evolution.

Evolutionary implication of human endogenous retrovirus HERV-H family

AbstractThe human endogenous retrovirus (HERV-H) family is most abundant and widely distributed in the human genome, with about 100-1,000 full-length or deleted elements and a similar number of solitary, long-terminal repeats. The HERV-H env ORF has been characterized in humans and in the course of primate evolution, indicating the increased possibility of biological roles in humans. Using the polymerase chain reaction approach with a human monochromosomal DNA panel, 70 envfragments belonging to the HERV-H family from chromosomes 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 14, 15, 16, 17, 18, 19, 20, X, and Y were identified and analyzed. They showed 82-99% sequence similarity to that of HERV-H (accession no. AF108843). We also identified other HERV-H envfragments in the DDBJ/EMBL/GenBank databases. The total of 120 fragments was evolutionarily analyzed. Phylogenetic analysis suggests that the HERV-H env family is divided into one major and two minor groups. The HERV-H members have been actively proliferated and evolved by intra-chromosomal spread during hominid radiation.

Isolation and Phylogenetic Analysis of HERV-K Long Terminal Repeat cDNA in Cancer Cells

Long terminal repeat (LTR) elements of human endogenous retrovirus (HERV-K) may have contributed to disease-associated structural change or genetic variation in the human genome. The LTR elements have been found to be coexpressed with sequences of closely located genes. We identified seven HERV-K LTR elements from mRNA of human cancer cells (HepG2, MCF7, and SiHa), using the RT-PCR approach. Four of them are closely related to the human-specific HERV-K LTR elements with a high degree of sequence homology in a neighbor-joining phylogenetic tree. The data suggest that recently proliferated HERV-K LTR elements are expressed actively in various cancer cells. These HERV-K LTR elements deserve further investigation as potential leads in the treatment of human cancer.

Long terminal repeats of porcine endogenous retroviruses in Sus scrofa

SummaryUsing PCR, sequencing, and bioinformatic approaches with the genomic DNAs of Korean pigs (domestic, wild, and hybrid with Yorkshire), twelve solitary PERV long terminal repeat elements were identified and analyzed. Structure analysis of the LTR elements indicated that they have different repeat sequences in the U3 region. The PERV-A6-KWP1 and -KWP2 elements bear seven and eight 39-bp repeats, respectively. The R region of the PERV LTR elements was highly conserved in pig and mouse genomes, suggesting that they seem to have originated from a common exogenous viral element and then evolved independently throughout the course of mammalian evolution.

Molecular cloning and phylogeny of HERV-E family that is expressed in japanese monkey (Macaca fuscata) tissues

Summary.More than 50 copies of HERV-E family have been estimated to exist in the human genome. Here, we examined the expression pattern and their relationships of the HERV-E in Japanese monkey tissues by RT-PCR and sequence analysis. The env gene of HERV-E family was expressed in monkey tissues (testis, prostate, kidney, thymus, intestine and stomach) except for cerebellum, pancreas and ovary, exhibiting that they may have transcriptional potential. Phylogenetic analysis of the HERV-E env family from Japanese monkey tissues and our previous data could be divided into two distinctive groups (I and II). They were integrated into the genomes of anthropoids and have evolved at the rate of 0.3% nucleotide differences per MYr through evolutionary divergence in primate evolution. Divergence times of the two groups were estimated as 11.6 MYr for group I and 41.6 MYr for group II. Those HERV-E sequences were extensively proliferated in the genome of humans and great apes. These data will contribute to further studies on the transcriptional potential of the HERV-E family in the Japanese monkey genome and to biomedical knowledge related to human diseases.

Identification and phylogenetic analysis of the human endogenous retrovirus HERV-W pol in cDNA library of human fetal brain

A human endogenous retroviral family (HERV-W) has recently been described that is related to multiple sclerosis-associated retrovirus (MSRV) sequences that have been identified in particles recovered from monocyte cultures from patients with multiple sclerosis. Two pol fragments (HWP-FB10 and HWP-FBl2) of HERV-W family were identified and analysed by the PCR approach with cDNA library of human fetal brain. They showed 89 percent nucleotide sequence similarity with that of the HERV-W (accession no. AF009668). Deletion/insertion or point mutation in the coding region of the pol fragments from human fetal brain resulted in amino acid frameshift that induced a mutated protein. Phylogenetic analysis of the HERV-W family from GenBank database indicates that the HWP-FB10 is very closely related to the AC000064 derived from human chromosome 7q21-q22. Further studies on the genetic relationship with neighbouring genes and functional role of these new HERV-W pol sequences are indicated.