Juergen Brosius at
Fri Sep 15 13:02:34 EST 1995

In article <ralph.1161056574B at>, ralph at (R M
Bernstein) wrote:

> there _are_ pseudogenes that are non-functional, ie not expressed, that are
> used and are important to the fitness of an organism...namely the VH genes
> in the rabbit.  they have 1 functional VH gene, meaning 1 gene that is
> expressed.  thay have , oh i dont know, maybe 15-20 (or more) other VH's
> that are the result of a probable duplication, that are all pseudogenes. 
> never expressed!  but, thru a process known as gene conversion
> (inotherwords-a miracle happened) the rabbits recombine or otherwise swap
> out their expressed VH gene for either: one of the pseudo-VHs or: a piece of
> one of the pseudo VHs.  and this produces the incredible diversity (also
> with somatic mut, etc) that we see in the rabbit antibody repitoire!  

There are other cases where assembly of parts of a *broken* gene can make a
functional gene.  I am citing from a review that I just finished:  

Another possibility of resurrecting inactive genes is recombination of
pseudogenes (or parts thereof) with active genes or other pseudogenes to
create novel gene variants, some interesting examples of which are already
known: The diversification of the light-chain preimmune repertoire is
achieved in the chicken by segmental gene conversions involving 25
pseudogenes as donors (Reynaud et al., 1987; McCormack et al., 1993).
Similarly, several pseudogenes -- all containing separate multiple stop
codons -- are pieced together by gene conversion, yielding functional
mosaic genes for late-appearing variable surface antigens in trypanosomes
(Longacre and Eisen, 1986; Roth et al., 1986, 1989). There is no indication
that the above pseudogenes have been created by retroposition. However,
formation of the 2V-II immunoglobulin gene has been generated in a murine
hybridoma, employing part of the germline VH108B retrogene (Stenzel-Poore
and Rittenberg, 1987). The potential for retrogenes in other yet to be
discovered examples is apparent (see also the Drosophila jingwei gene; Long
and Langley, 1993). Thus, retroposons may also represent a vast reservoir
for the creation of new gene variants by recombination with other inactive
pseudogenes, with active genes, or parts thereof.

Too often, a gene that originated by reverse transcription and
re-integration into the genome is earmarked as a pseudogene.  I know of at
least twelve examples where retrogenes did not end up as pseudogenes.  In
fact, most of the intronless genes of Eucarya may be of retroposon origin
(see also Baltimore [1985] Cell 40, 481-482 and Fink [1989] Cell 49, 5-6).

Short interspersed repetitive elements (SINEs) the epitomy of *junk DNA*
are nothing but retrogenes whose founders are small RNAs.  They are just
being more efficiently retroposed than mRNA-derived retrogenes.  Most of
them are neutral and some detrimental, depending on the site of
integration.  On the other hand, these SINEs - many of which are of tRNA
origin - are chockfull of DNA motifs that are potential protein binding
sites.  Many carry thus transcriptional enhancers or silencers to genes
that may - as a result - be regulated differentially.  Again, there is an
increasing number of such examples.  Also, SINEs can carry polyadenylation
signals, new splice sites or even amino acid codons to new locations and
thus alter resident genes (discussed e.g. in Brosius and Gould [1992] PNAS
89, 10706).

The term pseudogenes is unfortunate, since it keeps people from
contemplating their evolutionary potential.  The term dormant genes may be
more appropriate, yet is still not quite correct, since over time such
dormant genes are being modified by mutations during their state of
inactivity.  Such a variant dormant gene - sometimes so altered that its
origin cannot be deciphered anymore - can be anytime be recruited (exapted)
as a functional component of a gene.  For example, when it sits between two
exons it can be recruited as a third exon (Gilbert [1978] Nature 271, 501).

The frequently used analogy of non-coding DNA as the junkyard of evolution
is helpful - but not quite correct.  The DNA pieces (building blocks for
future uses) are constantly being remolden and reshaped.  Some of the
pieces get a trial in new combinations.  A fraction of those combinations
are beneficial.


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