Long Interspersed Elements (LINEs) Types and Distribution

Long INterspersed Elements (LINEs) comprise ~21% of human DNA and are grouped into three general classes (LINE-1, LINE-2 and LINE-3). The average human genome contains ~100 active (i.e. retrotransposition-competent) LINE-1 (L1) elements. LINE-2 and LINE-3 elements are ancient and are no longer retrotransposition-competent.

Active L1s encode two proteins (ORF1p and ORF2p) required for their retrotransposition by a mechanism termed target site primed reverse transcription. Most active human L1s belong to the Transcribed-Active (Ta) subfamily. Ta-subfamily L1s share diagnostic sequence characters, have amplified during the last 1-2 MY, and generally are polymorphic in humans. Ongoing L1 retrotransposition can lead to disease and 17/18 disease-producing L1 insertions are derived from the L1 Ta-subfamily.

L1s can impact the genome in a variety of ways. First, L1s can mobilize sequences derived from their 3’ flanks, and less commonly from their 5’ flanks, to new genomic locations by a process known as L1-mediated transduction. Second, L1-mediated recombination events, generated either during or after their integration, can result in genome instability. Third, L1 retrotransposition events into genes may alter gene expression by serving as premature polyadenylation sites, cryptic splice sites, or potentially RNA polymerase II stalling sites. Fourth, the L1-encoded proteins may function in trans to promote the retrotransposition of Short Interspersed Elements (SINEs), non-coding RNAs, and cellular mRNAs (discussed more in the Alu and SVA sections). Finally, recent studies also indicate that L1s can undergo retrotransposition in both early development and somatic tissues, and may lead to genetic mosaicism in individuals.

L1s continue to expand throughout the primate lineage. Two L1 lineages (LINE-1Pt-1 and LINE-1Pt-2) have specifically amplified the chimpanzee genome. The numbers of lineage specific L1 insertions are comparable between humans and chimps; however, the chimpanzee genome appears to contain twice as many polymorphic L1s as the human genome. These differences may reflect the greater effective ancestral population sizes for chimps when compared to humans.