Telomerase and retrotransposons: which came first?

TH Eickbush - Science, 1997 - science.org
TH Eickbush
Science, 1997science.org
Evolution is opportunistic. New cellular mechanisms can evolve from any genetic material
available within a cell. This adaptability means that self-replicating genetic elements, such
as transposable elements or viruses (cellular parasites), could be recruited for important
cellular functions. But this opportunism could work both ways. A gene that supplies a cellular
function could become a parasite, if given the ability to self-replicate. An important key to our
understanding of which scenario applies to telomeres—specialized structures at the ends of …
Evolution is opportunistic. New cellular mechanisms can evolve from any genetic material available within a cell. This adaptability means that self-replicating genetic elements, such as transposable elements or viruses (cellular parasites), could be recruited for important cellular functions. But this opportunism could work both ways. A gene that supplies a cellular function could become a parasite, if given the ability to self-replicate. An important key to our understanding of which scenario applies to telomeres—specialized structures at the ends of chromosomes—is provided on page 955 of this issue (1) and in a previous issue of Science (2). Because conventional DNA polymerases cannot complete the synthesis of both strands of a blunt-ended DNA template, early eukaryotes adopted the telomere as a mechanism to stably maintain the ends of linear chromosomes. The new reports provide a clear connection between telomerases, the enzymes that synthesize telomeres, and retrotransposons, small elements of DNA that can autonomously move from one part of the genome to another.
Eukaryotic telomeres are composed of tandem arrays of short nucleotide sequences (3). The probable mechanism of telomere sequence addition was first revealed by identification of the RNA subunit of telomerase and the demonstration that this RNA provides the template for nucleotide addition (4). A short region of the RNA subunit is repeatedly copied with the 3′ hydroxyl at the DNA terminus as a primer. Because the putative polymerase for telomere sequence addition uses an RNA template, it was postulated that this catalytic component could be similar to the reverse transcriptases encoded by retroviruses and retrotransposable elements. In a beautiful series of experiments that used a direct biochemical approach in Euplotes aediculatus and a genetic approach in Saccharomyces cerevisiae, the first telomerase catalytic subunits were identified (2). The S. cerevisiae protein was also implicated as a catalytic subunit in an independent study (5). By sequence homology this subunit has now also been identified in Schizosaccharomyces pombe and in humans, suggesting the universality of this subunit and the mechanism of telomere addition (1).
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