Jürgen Brosius

Institute of Experimental Pathology, University of Münster, Von-Esmarch-Str. 56, D-48149 Münster, Germany

Contact: Tel.:   +49-251-835-8511,     fax:   +49-251-835-8512,
E-mail:  RNA.world@uni-muenster.de

Conversion of genetic information from RNA into DNA by reverse transcription is ancient and was instrumental for the transition from the RNP world to modern cells (Brosius, 1999a, Nat. Genet. , 22, 8–9; Brosius, 2003, J. Struct. Funct. Genom. , 3, 1–17). Surprisingly, in many eukaryotic lineages, the process of retroposition is still very active. All types of RNAs (Brosius, 1999b, Gene , 238, 115–134) can be reverse transcribed and their cDNA copies reintegrated into genomes as retronuons (a nuon is any discrete segment of nucleic acid (Brosius and Gould, 1992, Proc. Natl Acad. Sci. USA , 89, 10706–10710)). About 38% or 42% of the mouse and human genomes, respectively, consist of discernible retronuons (excluding mRNA-derived retroposons). Only 1.5% of the human genome consists of exons coding for proteins. Even considering DNA transposons (1–3% discernible), slippage during replication and a relatively large fraction derived from segmental duplications it is conceivable that the remainder of mammalian genomes is probably derived from ancient, today non-discernible retronuons. Hence, the vast majority of mammalian genomes have been contributed by retroposition. Retroposition predominantly leads to ‘junk DNA’. However, mRNA-derived retronuons are known to give rise to active genes, often with different expression patterns than their respective founder genes (Brosius and Gould, 1992, Proc. Natl Acad. Sci. USA , 89, 10706–10710; Brosius, 1991, Science , 251, 753). Retronuons derived from small non-messenger RNAs (snmRNAs) generate novel snmRNA genes (such as the neuron-specific BC1 and BC200 RNAs) (Brosius, 1999b, Gene , 238, 115–134; Brosius and Gould, 1992, Proc. Natl Acad. Sci. USA , 89, 10706–10710). Frequently, retronuons are exapted (co-opted) as regulatory elements that may alter expression or processing of targeted genes (Brosius and Gould, 1992, Proc. Natl Acad. Sci. USA , 89, 10706–10710) (for compilations see:
http://www-ifi.uni-muenster.de/exapted-retrogenes/tables.html  ).
Consequently, retronuons are a major driving force of evolution and perhaps even speciation. Comparison of the human genome with that of other mammals such as mouse or, in particular, chimpanzee reveals that neither contains numerous additional genes. Instead, one observes exaptation of novel exons (often involving alternative splicing) from previously nonaptive intronic (as predicted by Gilbert, 1978, Nature , 271, 501) or flanking sequences originally generated by retroposition. Furthermore, the differential expression of shared genes with respect to developmental onset and/or cell-type specificity, that is triggered by de novo insertions of retronuons, will turn out to be a recurrent theme in species differences at the genomic level.

References:

1. Brosius J, (1991), "Retroposons - seeds of evolution",  Science,vol.  251: 753.

2. Brosius J, and Gould SJ, (1992), "On Genomenclature: A comprehensive (and respectful) taxonomy for pseudogenes and other 'junk' DNA", Proc. Natl. Acad. Sci. USA, vol. 89: 10706-10710.

3. Brosius J, (1999a), "Transmutation of tRNA over time", Nature Genetics, vol. 22; 8-9.

4. Brosius J, (1999b), "RNAs from all categories generate retrosequences that may be exapted as novel genes or regulatory elements", Gene, vol. 238: 115-134.

5. Brosius J, (2003), "Gene duplication and other evolutionary strategies: from the RNA world to the future", J. Struct. Funct. Genom. vol. 3, 1-17.

6. Gilbert W, (1978), "Why genes in pieces?" Nature vol. 271, 501.

Additional References:

1. DeCarvalho S, "Effect of RNA from Normal Human Marrow on Leukemic Marrow In-Vivo".

2. Gottesfeld JM,  and Barbas CF III, "RNA as a Transcriptional Activator".

3. Frenster JH, and Hovsepian JA, "Overshoot in Late Telophase for RNA Re-Programming of Mitotic Chromatin".

4. Hovsepian JA, and Frenster JH, "RNA-Induced Melting of DNA during Selective Gene Transcription".

5. Saha S, Ansari AZ, Jarell KA, and Ptashne M, "RNA Sequences that Work as Transcriptional Activating Regions".

6. Cavaille J, Buiting K, Kiefmann M, Lalande M, Brannan CI, Horsthemke B, Bachellerie J-P, Brosius J, and Huttenhofer A, "Identification of Brain-Specific and Imprinted Small Nucleolar RNA Genes Exhibiting an Unusual Genomic Organization".

7. Skryabin BV, Sukonina V, Jordan U, Lewejohann L, Sachser N, Muslimov I, Tiedge H, Brosius J., "Neuronal untranslated BC1 RNA: targeted gene elimination in mice",  Mol Cell Biol. 2003 Sep;23(18):6435-41.

8. Frenster JH, "Ultrastructural Probes of Active DNA Sites, and the RNA Activators of DNA".