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 element s (LINEs) have amplified to a copy number of about 100,000 over the last 10 0 million years of mammalian evolution and comprise similar to 15% of the h uman genome. The majority of LINE-1 (L1) elements within the human genome a re 5' truncated copies of a few active LI elements that are capable of retr otransposition. 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 evolu tion studies. First, they are typed by rapid, simple, polymerase chain reac tion (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 nucleot ides. 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 di splay for the direct identification of dimorphic L1 elements from the human genome, We have also developed PCR-based assays for the characterization o f six polymorphic Il elements within the human genome. PCR analysis of huma n/rodent hybrid cell line DNA samples showed that the polymorphic tl elemen ts were Located on several different chromosomes. Phylogenetic analysis of nonhuman primate DNA samples showed that all of the recently integrated "yo ung" L1 elements were restricted to the human genome and absent from the ge nomes of nonhuman primates. Analysis of a diverse array of human population s showed that the allele frequencies and revel of heterozygosity for each o f the II elements was variable. Polymorphic LI elements represent a new sou rce of identical-by-descent variation for the study of human evolution.