RNA-Dependent Synthesis of RNA and DNA:- Many Transposons, Retroviruses, and Introns May Have a Common Evolutionary Origin
Some well-characterized eukaryotic DNA transposons from sources as diverse as yeast and fruit flies have a structure very similar to that of retroviruses; these are sometimes called retrotransposons (Fig. 1). Retro transposons encode an enzyme homologous to the retro viral reverse transcriptase, and their coding regions are flanked by LTR sequences. They transpose from one position to another in the cellular genome by means of an RNA intermediate, using reverse transcriptase to make a DNA copy of the RNA, followed by integration of the DNA at a new site. Most transposons in eukaryotes use this mechanism for transposition, distinguishing them from bacterial transposons, which move as DNA directly from one chromosomal location to another .
FIGURE 1 Eukaryotic transposons. The Ty element of the yeast Saccharomyces and the copia element of the fruit fly Drosophila serve as examples of eukaryotic transposons, which often have a structure similar to retroviruses but lack the envgene. The sequences of the Ty element are functionally equivalent to retroviral LTRs. In the copia element, int and RTare homologous to the integrase and reverse transcriptase segments, respectively, of the pol gene.
Retrotransposons lack an envgene and so cannot form viral particles. They can be thought of as defective viruses, trapped in cells. Comparisons between retro viruses and eukaryotic transposons suggest that reverse transcriptase is an ancient enzyme that predates the evolution of multicellular organisms.
Interestingly, many group I and group II introns are also mobile genetic elements. In addition to their self-splicing activities, they encode DNA endonucleases that promote their movement. During genetic exchanges between cells of the same species, or when DNA is introduced into a cell by parasites or by other means, these endonucleases promote insertion of the intron into an identical site in another DNA copy of a homologous gene that does not contain the intron, in a process termed homing (Fig. 2). Whereas group I intron homing is DNA-based, group II intron homing occurs through an RNA intermediate. The endonucleases of the group II introns have associated reverse transcriptase activity. The proteins can form complexes with the intron RNAs themselves, after the introns are spliced from the primary transcripts. Because the homing process involves insertion of the RNA intron into DNA and reverse transcription of the intron, the movement of these introns has been called retro homing. Over time, every copy of a particular gene in a population may acquire the intron.
FIGURE 2 Introns that move: homing and retrohoming. Certain introns include a gene (shown in red) for enzymes that promote homing (type I introns) or retrohoming (type II introns). (a) The gene within the spliced intron is bound by a ribosome and translated. Type I homing introns specify a site-specific endonuclease, called a homing en donuclease. Type II retrohoming introns specify a protein with both endonuclease and reverse transcriptase activities. (b) Homing. Allele a of a gene X containing a type I homing intron is present in a cell containing allele b of the same gene, which lacks the intron. The homing endonuclease produced by a cleaves b at the position corresponding to the intron in a, and double-strand break repair then creates a new copy of the intron in b. (c) Retrohoming. Allele a of gene Y contains a retrohoming type II intron; allele b lacks the intron. The spliced intron inserts itself into the coding strand of b in a reaction that is the reverse of the splicing that excised the intron from the primary transcript , except that here the insertion is into DNA rather than RNA. The noncoding DNA strand of b is then cleaved by the intron-encoded endonuclease/reverse transcriptase. This same enzyme uses the inserted RNA as a template to synthesize a complementary DNA strand. The RNA is then degraded by cellular ribonucleases and replaced with DNA.
Much more rarely, the intron may insert itself into a new location in an unrelated gene. If this event does not kill the host cell, it can lead to the evolution and distribution of an intron in a new location. The structures and mechanisms used by mobile introns support the idea that at least some introns originated as molecular parasites whose evolutionary past can be traced to retro viruses and transposons.
