Retroelements and the human genome: new perspectives on an old relation

Abstract

Retroelements constitute a large portion of our genomes. One class of these elements, the human endogenous retroviruses (HERVs), is comprised of remnants of ancient exogenous retroviruses that have gained access to the germ line. After integration, most proviruses have been the subject of numerous amplifications and have suffered extensive deletions and mutations. Nevertheless, HERV-derived transcripts and proteins have been detected in healthy and diseased human tissues, and HERV-K, the youngest, most conserved family, is able to form virus-like particles. Although it is generally accepted that the integration of retroelements can cause significant harm by disrupting or disregulating essential genes, the role of HERV expression in the etiology of malignancies and autoimmune and neurologic diseases remains controversial. In recent years, striking evidence has accumulated indicating that some proviral sequences and HERV proteins might even serve the needs of the host and are therefore under positive selection. The remarkable progress in the analysis of host genomes has brought to light the significant impact of HERVs and other retroelements on genetic variation, genome evolution, and gene regulation.

Fig. 1.

Classification of transposable elements. The percentage of each element in the genome and the estimated number of the elements of the main groups are indicated.

Fig. 2.

Structural features of important retroelements. Arrows indicate repeat sequences generated during the integration process. Filled squares represent promoter regions, and A-runs indicate original polyadenylation. The usual length of the respective element is shown in parentheses.

Fig. 3.

Genomic organization and transcript pattern of HERV-K. (A) The structure of a type 2 HERV-K is shown. (Right) A Northern blot with mRNA of a teratocarcinoma cell line, probed with a labeled HERV-specific cDNA. (B) Schematic representation of the splicing events resulting in rec (HERV-K type 2) and np9 (HERV-K type 1) specific mRNAs. The proviruses differ in a 292-bp deletion (Δ292 bp) that contains the splice donor site used to generate the rec transcripts (SD “b”). An alternative upstream splice donor site (SD “a”) is used for np9 messages. The numbers within the boxes refer to the coding reading frame. (This part of the figure has been redrawn with modifications from ref. .)

Fig. 4.

Electron microscopic analysis of HERV-K/HTDV particles produced by teratocarcinoma cell lines. Micrographs courtesy of K. Boller, Paul-Ehrlich-Institut (Langen, Germany). (Scale bar, 200 nm.)