Reading between the LINEs: Human genomic variation induced by LINE-1 retrotransposition

The insertion of mobile elements into the genome represents a new class of genetic markers For the study of human evolution. Long interspersed elements (LINEs) have amplified to a copy number of about 100,000 over the last 100 million years of mammalian evolution and comprise similar to 15% of the human genome. The majority of LINE-1 (L1) elements within the human genome are 5' truncated copies of a few active LI elements that are capable of retrotransposition. Some of the young L1 elements have inserted into the human genome so recently that populations are polymorphic for the presence of an Lf element at a particular chromosomal location. LI insertion polymorphisms offer several advantages over other types of polymorphisms for human evolution studies. First, they are typed by rapid, simple, polymerase chain reaction (PCR)-based assays. Second, they are stable polymorphisms that rarely undergo deletion. Third, the presence of an II element represents identity by descent, because the probability is negligible that two different young LI repeats would integrate independently between the exact same two nucleotides. Fourth, the ancestral state of L1 insertion polymorphisms is known to be the absence of the LI element, which can be used to root plots/trees of population relationships. Here we report the development of a PCR-based display for the direct identification of dimorphic L1 elements from the human genome, We have also developed PCR-based assays for the characterization of six polymorphic Il elements within the human genome. PCR analysis of human/rodent hybrid cell line DNA samples showed that the polymorphic tl elements were Located on several different chromosomes. Phylogenetic analysis of nonhuman primate DNA samples showed that all of the recently integrated "young" L1 elements were restricted to the human genome and absent from the genomes of nonhuman primates. Analysis of a diverse array of human populations showed that the allele frequencies and revel of heterozygosity for each of the II elements was variable. Polymorphic LI elements represent a new source of identical-by-descent variation for the study of human evolution.