Transposable elements and the evolution of eukaryotic genomes.

W hen transposable elements (TEs) were discovered in maize by Barbara McClintock 50 years ago they were regarded as a curiosity; now they are known to be the most abundant component of probably all eukaryotic genomes. They account for almost 50% of the human genome and 70% of the genomes of some grass species, including maize. As such, they make up the vast majority of the output of genome sequencing projects. The availability of so much new information has fueled a revolution in their analysis and studies of their interaction with the host. In addition to discovering TEs, McClintock also uncovered disparate ways that TEs can alter genetic information. At one end of the spectrum she found that TEs could restructure genomes through element-mediated chromosomal rearrangements. At the other end she and others found they could generate new alleles by inserting into and around genes and altering their expression. Thus, the presence and extraordinary abundance of TEs in eukaryotic genomes promote a myriad of genome-altering events. TEs are fragments of DNA that can insert into new chromosomal locations, and they often make duplicate copies of themselves in the process. Eukaryotic TEs are divided into two classes, according to whether their transposition intermediate is RNA (class 1) or DNA (class 2) (Fig. 1). For all class 1 elements, the element-encoded transcript (mRNA) forms the transposition intermediate. In contrast, with class 2 elements, the element itself moves from one site to another in the genome. Each group of TEs contains autonomous and nonautonomous elements. Autonomous elements have ORFs that encode the products required for transposition. In contrast, nonautonomous elements do not encode transposition proteins but are able to transpose because they retain the cis sequences necessary for transposition. Integration of almost all TEs results in the duplication of a short genomic sequence (called a target site duplication, or TSD) at the site of insertion. Eukaryotic DNA (class 2) transposons usually have a simple structure with a short terminal inverted repeat (TIR) ( 10–40 bp, but can be up to 200 bp) and a single gene encoding the transposase. Transposase binds in a sequence-specific manner to the ends of its encoding element and to the ends of nonautonomous family members. Once bound, transposase initiates a cut-andpaste reaction whereby the element is excised from the donor site (generating an ‘‘empty site’’) and inserted into a new site in the genome. The elements studied by McClintock, including the Ac Ds and Spm dSpm families, are DNA transposons capable of insertion and excision. Class 1 retroelements can be divided into two groups on the basis of transposition mechanism and structure. LTR retrotransposons have long terminal repeats (LTRs) in direct orientation that can range in size from 100 bp to several kilobases. Autonomous elements contain at least two genes, called gag and pol. The gag gene encodes a capsidlike protein, and the pol gene encodes a polyprotein that is responsible for protease, reverse transcriptase, RNase H, and integrase activities. An elementencoded transcript that initiates from a promoter in the 5 LTR and terminates in the 3 LTR is transported to the cytoplasm. There it serves as both mRNA and template for double-stranded cDNA that is transported into the nucleus where it can then integrate into the genome. The host can mitigate this increase in genome size by mediating homologous recombination between the identical or near-identical LTRs of fulllength elements, generating a much shorter solo LTR. LTR retrotransposons compose the largest fraction of most plant genomes, where they appear to be the major determinant of the tremendous variation in genome size. Non-LTR retrotransposons are divided into the autonomous long interspersed elements (LINEs) and the nonautonomous short interspersed elements (SINEs). LINEs encode two ORFs, which are transcribed as a bicistronic mRNA composed of ORF1 (an RNA binding protein) and ORF2 (endonuclease and reverse transcriptase activities). Both LINEs and SINEs terminate by a simple sequence repeat, usually poly(A). LINE transcripts initiate at a promoter within the 5 end of the element and terminate at or often downstream of the simple repeat sequence. SINEs are characterized by an internal RNA pol III