HERV-K (HML-2) Insertions Distinguishing Human Genome from Non-Human Primates



B. Lebedev


Institute of Bioorganic Chemistry, Russ.Acad.Sci.,


Miklukho-Maklaya str., 117997 Moscow, Russia

Phone: +7 (095) 330

6329  FAX:    +7 (095) 330 6538  e-mail: [email protected]



Retroelements (REs) of human genome bear crucial information about evolutionary

events. Thus, the identification of human specific integrations in the vicinity

of human genes, especially those involved in embryo development, could reveal

the REs which possibly played a role in the split of the human and other

hominoid lineages. In particular, ongoing integrations of Human Endogenous

Retroviruses (HERVs) and their activities could be a key factor of primate

genome evolution.


perform genome-wide comparison of RE integration site and RE activity

distinguishing closely related genomes we developed experimental approaches. A

method consists of (i) a whole genome selective amplification of the flanks

adjacent to target REs, and (ii) further analysis of obtained sequences using

subtractive hybridization, differential display, and differential hybridization

screening techniques.


of developed methods was applied for the detection of differences between the

human (H. sapience) and chimpanzee (P. troglodytes) genomes those

occurred due to HERV-K retrotranspositions. Over 80 LTRs human specific elements

were identified. Further phylogenetic analysis of the LTR sequences allowed us

to predict simultaneous retrotransposition activity of at least 3 distinct

‘master genes’ during hominid evolution. Total amount of the human specific LTRs

was estimated at the level of 120-150, and corresponding insertions were

searched from the draft of human genome. About 30% of the identified LTRs were

mapped in close vicinity or within introns of human genes. We found

human-specific HERV-K LTRs integrations in introns of 17 human genes most of

them oriented in opposite direction relative to the gene transcription.


second technique was used to compare the transcription level of human endogenous

retroviruses (HERV‑K) LTRs in testicular germ cell tumors and their normal

tissue counterparts. The result enabled us to get an overview of individual LTRs

within the whole-genome transcribed fraction and to reveal differences in

transcription patterns of the LTRs in normal and tumor tissues. An unexpectedly

large number of the LTRs was found to be transcribed. The content of many of the

transcripts being different in normal and tumor tissues. The data obtained

indicate that an appreciable fraction of the LTRs retained the regulatory

potential through millions of years of the evolution and thus may contribute to

the overall transcription regulatory network.

Methylation profiles of loci containing the human specific LTRs were

investigated in several human tissues and cell lines. With the use the developed

technique we found that many human-specific LTRs are differentially methylated

in human tissues and possibly their methylation status could be linked with

expression of adjacent genes.