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  Topic: The Origin of "Information" via natural causes, Refuting a key ID claim (refs, webpages)< Next Oldest | Next Newest >  

Posts: 97
Joined: May 2002

(Permalink) Posted: Aug. 26 2003,18:18   

Evidence of more retrogenes in the human genome.    

Nucleic Acids Res. 2003 Aug 1;31(15):4385-90.

The human genome contains many types of chimeric retrogenes generated through in vivo RNA recombination.

Buzdin A, Gogvadze E, Kovalskaya E, Volchkov P, Ustyugova S, Illarionova A, Fushan A, Vinogradova T, Sverdlov E.

L1 retrotransposons play an important role in mammalian genome shaping. In particular, they can transduce their 3'-flanking regions to new genomic loci or produce pseudogenes or retrotranscripts through reverse transcription of different kinds of cellular RNAs. Recently, we found in the human genome an unusual family of chimeric retrotranscripts composed of full-sized copies of U6 small nuclear RNAs fused at their 3' termini with 5'-truncated, 3'-poly(A)-tailed L1s. The chimeras were flanked by 11-21 bp long direct repeats, and contained near their 5' ends T2A4 hexanucleotide motifs, preferably recognized by L1 nicking endonuclease. These features suggest that the chimeras were formed using the L1 integration machinery. Here we report the identification of 81 chimeras consisting of fused DNA copies of different RNAs, including mRNAs of known human genes. Based on their structural features, the chimeras were subdivided into nine distinct families. 5' Parts of the chimeras usually originated from different nuclear RNAs, whereas their 3' parts represented cytoplasmic RNAs: mRNAs, including L1 mRNA and Alu RNA. Some of these chimeric retrotranscripts are expressed in a variety of human tissues. These findings suggest that RNA-RNA recombination during L1 reverse transcription followed by the integration of the recombinants into the host genome is a general event in genome evolution.

To remind everyone, retrogenes are created as follows:

1.  mRNA from existing gene --> reverse transcription into cDNA.

This is carried out by an endogenous reverse transcriptase, which may come from endogenous retroviruses, Alu elements, etc.

2.  cDNA is integrated into genome.

This is also carried out by endogenous integration proteins.  Again, these can also come from endogenous retroviruses, etc.

The result is a gene duplicate that usually has the following attributes:

A.  No introns.
B.  Trucated at the 5' end.
C.  The remnants of a poly-A tail at the 3' end.
D.  Flanking repeats.

These attributes make identifying retrogenes relatively easy, and they provide extremely strong evidence that these genes did indeed arise through retrotransposition.  Given that they contain a truncation, and are integrated without regulatory sequences, the most common fate for a retroelement of this kind is to be non-functional.  However, examples of functional retrogenes exist.  

The chimeras observed in the present study are formed when an RNA-RNA hybrid, consisting of two unrelated RNA transcripts, is acted upon by a reverse transcriptase.  Here is the proposed mechanism:

Figure 4. A probable mechanism for the chimeras’ formation. (Step 1) An L1 pre-integration complex binds L1, Alu or the host mRNA in the cytoplasm. (Step 2) The ribonucleoprotein formed is transferred to the nucleus. (Step 3) Reverse transcription of the bound mRNA primed by a genomic DNA single-stranded break within the TTTTAA sequence. (Step 4) Another (nuclear) RNA binds to the L1 reverse transcription/integration complex. (Step 5) Switch of templates for the reverse transcription. (Step 6) The DNA reparation mediated formation of a new chimeric retrogene insertion flanked by short direct repeats and carrying a poly(A) sequence at the 3' terminus.

The authors found that at least 6 of the chimeric retrogenes that they found (out of 81) are being expressed in human tissues, indicating that they likely have a function.  Whether or not the rest have a function isn't known, but the authors only directly tested (via RT-PCR analysis) 6 of the sequences and found that 4 were unexpressed.  So these identified retroelements probably contain a mixture of functional and non-functional sequences.

Moreover, the presence of these chimeric retrogenes also provides evidence for common descent, since they have integrated at various times during primate evolution, and yet they follow the standard phylogeny:

Figure 3. Results of the 12 chimeric retrogenes insertional polymorphism study. The chimeras’ integration times were estimated according to the presence/ absence of the inserts in genomic DNAs of different primate species.

One of the retrogenes is polymorphic within the human population, indicating that it arose since the last common ancestor of all humans.

This is very strong evidence for common descent, along the lines of shared errors in pseudogenes.  


Edited by theyeti on Aug. 26 2003,18:19

  42 replies since May 30 2002,00:02 < Next Oldest | Next Newest >  

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