[New mechanism of retrogene formation in mammalian genomes: in vivo recombination during RNA reverse transcription].

L1 LINE retrotransposons play an important role in the shaping and permanent evolution of mammalian genomes. In particular, occupying about 20% of genomic DNA, they transduce their 3' flanking sequences to new genomic loci and create pseudogenes by reverse transcribing different kinds of cellular RNAs. Recently we discovered in mammalian genomes several families of chimeric pseudogenes, consisting of fused copies of various cellular transcripts. The characteristic peculiarities of such chimeric inserts suggest the involvement of L1 enzymatic machinery in their formation. The detailed sequence analysis revealed that 5' terminal parts of the chimeras are copies of nuclear RNAs, while 3' terminal sequences were formed on the templates of transcripts having cytoplasmic orientation. These data enabled us to propose the mechanism for the chimeras formation, comprising the switch of templates during RNA reverse transcription by L1 reverse transcriptase. The further identification of not only "double", but also "triple" chimeric retrogenes evidences the possibility of the double template switches as well. Some of the found chimeras are transcriptionally active, thus allowing to consider the discovered phenomenon as the new mechanism of the gene formation by "shuffling" of pre-existing transcribed sequences. Being active in mammals now, the mechanism appeared at least 75 million years ago and is evolutionary conserved.