The human genomic sequence is a gold mine for new discoveries in molecular cell biology, for identifying new proteins that may be the basis of effective therapies of human diseases, and for understanding early human history and evolution. However, finding new genes is like finding a needle in a haystack, because only about 1.5 percent of the human genome encodes proteins or functional RNAs. Identification of genes in bacterial genomic sequences is relatively simple because of the scarcity of introns; simply searching for open reading frames identifies most genes. In contrast, the search for human genes is complicated by the structure of our genes, most of which are composed of multiple, relatively short exons separated by much longer noncoding introns. Identification of complex transcription units by analysis of genomic DNA sequences alone is extremely challenging. Future improvements in bioinformatic methods for gene identification, as well as characterization of cDNA copies of mRNAs isolated from the hundreds of human cell types, is likely to lead to the discovery of new proteins, to a better understanding of biological processes, and possibly to applications in medicine and agriculture.

We have seen that although most transposons do not function directly in cellular processes, they have helped to shape modern genomes by promoting gene duplications, exon shuffling, and the generation of new combinations of transcription-control sequences. They are also teaching us about our own history and origins. L1 and Alu retrotransposons have inserted into new sites in individuals throughout our history. Large numbers of these interspersed repeats are polymorphic within populations, occurring at a particular site in some individuals and not in others. Individuals sharing an insertion at a particular site must have descended from a common ancestor who developed from an egg or sperm in which that insertion occurred. The time elapsed from the initial insertion can be estimated by the sequence differences in the element that have arisen from the accumulation of random mutations. Further analysis of retrotransposon polymorphisms will undoubtedly add immensely to our understanding of human migrations since Homo sapiens first evolved as well as the history of contemporary populations.

As described in Chapter 6, a Drosophila DNA transposon called the P element has been exploited for the facile stable transfection of genes into the Drosophila germ line. This transposon has provided a powerful method for molecular cell biology experimentation in Drosophila. An active area of current research is the use of mammalian transposons and retrotransposons for the transformation of human cells for gene therapy. This promises to be an exciting area of medicine in the future treatment of genetic diseases such as sickle-cell disease and cystic fibrosis as well as more common diseases, especially when coupled with the recently developed techniques for generating pluripotent stem cells (iPS cells) from differentiated cells of a pediatric or adult patient (see Chapter 21).