Introduction
Transposable elements (TEs), mobile segments of genetic material, were first discovered by McClintock [1]. Since then, they have been identified in a variety of eukaryotes [2]. Recent genome sequencing projects have consistently shown that TEs make up ~50% of primate genomes, while coding DNA occupies only ~2% of the genomes [3-5]. TEs are generally divided into two categories, DNA transposons and retrotransposons (Fig. 1), based on their manner of mobilization. DNA transposons move using a cut-and-paste mechanism [6]. In contrast, retrotransposons move in a copy-and-paste fashion by duplicating the element into a new genomic location via an RNA intermediate [7]. Thus, retrotransposons increase their copy number more rapidly than DNA transposons.
Retrotranspons include short interspersed element (SINE), long interspersed element (LINE), and human endogenous retrovirus (HERV). Alu and short interspersed element/variable number of tandem repeats/Alu (SVA) elements are primate-specific retrotransposons, and their full-length is 300 bp and 2 kb, respectively. The Alu element is the most successful SINE in terms of its copy number; ~1.2 million Alu copies exist in the human genome. LINE is ~6 kb in length, and thus, it is much longer than the SINEs. This element has two open reading frames encoding enzymatic machineries essential for the propagation of the three elements; the Alu element depends on reverse transcriptase of LINE for making their dispersed copies in the host genome [8]. In contrast to SINE and LINE, which do not have long terminal repeats (LTRs), the full-length HERV (~10 kb) has two LTRs, and three genes-gag, pol, and env-are located between them [8, 9].
Studies on active TEs have suggested that the elements could alter gene expression by providing cis-regulatory elements, such as promoters, enhancers, and transcription factor binding sites [10]. Through these mechanisms, altered transcriptional activity could lead to dysfunctional and abnormal proteins. Through de novo TE insertion within a gene, TEs could alter a gene product, which could be either harmful or beneficial to its host genome [11, 12]. In cases where an inserted TE causes a harmful effect on its host genome, the TE is likely to go to inactivation and fossilization by evolutionary accumulation of mutations and silencing effects [13].
Since the divergence of the human and chimpanzee, ~6 million years ago, many TEs have propagated in each genome. Among them are the Alu, L1, SVA, and HERV-K (HML-2) elements. During the past 6 million years, 5,530 Alu, 1,835 L1, 864 SVA, and 113 HERV-K (HML-2) elements are estimated to have been newly inserted in the human genome (Table 1) [8, 14, 15]. These elements could act as an agent causing human-specific genomic rearrangements via de novo TE insertions, TE insertion-mediated deletions, and homologous recombination events [12, 16-19]. Furthermore, some of the recent integrated TEs are capable of producing new copies in the human genome. These de novo TE insertions have the potential to cause a genomic difference among human populations and even human individuals, which could be related to human phenotypes and diseases [20].
In this review, we describe species-specific TEs and discuss how they affect their host genomes, focusing on illustrating the mechanisms that they utilize with examples. Taken together, we suggest that TEs, often called 'junk' DNA, in fact have many functions and play a significant and dynamic role in primate genomic evolution.