Retrotransposons, reverse transcriptase and the genesis of new genetic information

Abstract

Spermatozoa of virtually all species can take up exogenous DNA or RNA molecules and internalize them into nuclei. A sperm endogenous reverse transcriptase activity can reverse-transcribe the internalized molecules in cDNA copies: exogenous RNA is reverse-transcribed in a one-step reaction, whereas DNA is first transcribed into RNA and subsequently reverse-transcribed. In either case, the newly synthesized cDNAs are delivered from sperm cells to oocytes at fertilization and are further propagated throughout embryogenesis and in tissues of adult animals. The reverse-transcribed sequences are underrepresented (below 1 copy/genome), mosaic distributed in tissues of adult individuals, transmitted in a non-Mendelian fashion from founders to F1 progeny, transcriptionally competent, variably expressed in different tissues and temporally transient, as they progressively disappear in aged animals. Based on these features, the reverse-transcribed sequences behave as extrachromosomal, biologically active retrogenes and induce novel phenotypic traits in animals. This RT-dependent mechanism, presumably originating from LINE-1 retroelements, generates transcriptionally competent retrogenes in sperm cells. These data strengthen the emerging view of a novel transgenerational genetics as the source of a continuous flow of novel epigenetic and phenotypic traits, independent from those associated to chromosomes. The distinctive features of this retrotransposon-based phenomenon share analogies with a recently discovered form of RNA-mediated inheritance, compatible with a Lamarckian-type adaptation.