Summary

Mobile DNA elements within the human genome are in almost all cases inactive and represent a 'fossil record' in our DNA reflecting past transposition events. They constitute a remarkable 45% of human genomic sequence and have contributed greatly to the complexity and plasticity of our genome, and that of our primate and earlier ancestors. No evidence of transposase activity is found in the anthropoid lineage for 37 million years, but intense activity is believed to have taken place early in primate evolution (Pace and Feschotte 2007). The consequences of transposition can be profound, leading for example to the generation of new genes through fusion events, as illustrated by the birth of the SETMAR gene in primates some 40-58 million years ago involving a mariner mobile element (Cordaux et al. 2006).

The dispersal and accumulation of transposable elements are believed to have had a dramatic influence on the evolution of eukaryotic genomes. They have the capacity to introduce significant diversity into the genome and the potential to serve as building blocks for coordinated regulatory networks, as illustrated by the dispersal of specific transcription factor binding sites within mobile elements for the master regulator p53 (Wang et al. 2007; Feschotte 2008). Elsewhere there is recent evidence of how specific SINEs may have generated important regulatory enhancer elements for the POMC and ISL1 genes some 170 and 410 million years ago, respectively (Bejerano et al. 2006; Santangelo et al. 2007).

Mobile DNA elements are seen as genomic parasites, surviving as they replicate faster than the host genome in which they are found (Brookfield 2005). Within this diverse group, Alu elements are themselves parasites of LINEs, relying as they do on active L1 elements for the proteins they require to replicate. Over 99.8% of the more than 500 000 copies of L1 elements in our genome are inactive; polymorphism is recognized among human populations for the 80-100 competent L1s (Brouha et al. 2003). Similarly, only a small number of competent ' master' Alu elements are found among the more than 1 million Alu insertions in the human genome. A diverse range of human genetic diseases may result from either L1 or Alu element insertions -ranging from haemophilia (factor VIII gene) (Kazazian et al. 1988) to colon cancer (APC gene) (Miki et al. 1992) with L1s, and to breast cancer (BRCA2) (Miki et al. 1996), neurofibromatosis (NF1) (Wallace et al. 1991), and Apert syndrome (FGFR2) (Oldridge et al. 1999) with Alu insertions. Alu elements are also an important substrate for homologous recombination, which may lead to deleterious deletions, and for unstable repeats.

Polymorphism among recent Alu elements and other mobile DNA elements has been a very important tool in our understanding of human population genetics and evolutionary history, as illustrated by work on human origins and support for the Recent African Origins

| 1 Archaic deme

^^ Transition to anatomically modern humans

1 1 Anatomically modern humans

| Extinction event

^ Gene flow

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