Pseudogene
Pseudogenes are DNA segments that are structured like a gene , but no longer serve as a template for a functional protein.
Formation of pseudogenes
A small number of pseudogenes are believed to have been functioning genes and have been overridden by mutations. Most pseudogenes, however, are functionless duplicates of functioning genes. The inoperability of a pseudogene could have arisen in two different ways:
- The pseudogene was already inoperable from the start (i.e. immediately after the gene duplication ) because serious errors occurred during the duplication process.
- In the beginning, the pseudogene worked exactly like its original, but then more and more mutations accumulated over time, so that the duplicate slowly became functionless.
In addition to the formation of pseudogenes through gene duplication , the possibility of retrotransposition is also discussed. The reverse transcription of mRNA of functioning genes creates double-stranded DNA, which is then incorporated somewhere in the genome. Pseudogenes that arose in this way no longer have any introns , since the underlying mRNA also no longer contained any introns (RNA splicing). These intron-less pseudogenes are also referred to as processed pseudogenes.
Importance of pseudogenes
Both ways described above - duplication and retrotransposition - can increase the number of genes in a living being. However, the duplicated gene is not subjected to the same selection pressure as the original gene, since a failure of the duplicate is no longer tragic if the original gene is still working. Mutations can therefore accumulate relatively easily in the duplicate. These can quickly make the duplicate functionless again (and thus transform it into a pseudogene) without this having any negative effects on the phenotype . On the other hand, mutations in the duplicated genes also enable the emergence of new, advantageous characteristics. For example, the green opsin genes of mammals emerged from the red opsin genes by gene duplication.
Pseudogenes of ribosomal proteins
Some types of genes can become pseudogenes particularly easily. Only 1/4 of all known gene families have produced pseudogenes. This is particularly extreme with the genes for ribosomal proteins. There are around 80 genes that encode ribosomal proteins. These 80 genes have produced over 2000 pseudogenes, i.e. 1/10 of all known pseudogenes. An extreme case is the RPL21 gene, of which there are more than 140 pseudogenes.
Pseudogenes and selection pressure
When pseudogenes are really useless, they are no longer subject to selection pressure. So over time, tons of mutations should pile up randomly. It has now been shown, however, that there are pseudogenes that are fairly conserved, that is, they have hardly changed. This strongly suggests that a selection pressure was effective here, as we know it from important “real” genes. This suggests that - at least some - pseudogenes do have a function. In this case, however, the pseudogenes would have to be transcribed. In fact, it has been found that approximately 10% of the pseudogenes are transcribed.
A new study discusses the function of some pseudogenes as regulators of miRNAs . It was shown that the 3 ' UTR of a tumor suppressor pseudogene ( PTENP1 ) has binding sites for miRNAs that also bind to its related protein-coding gene ( PTEN ). The miRNAs sequestered on the pseudogene can no longer affect the coding gene, which results in a certain down-regulation of the miRNA effect.
Possible functions of the pseudogene mRNA
The mRNA of pseudogenes can be used as regulatory RNA affect real Gene transcription (or translation).
- Example 1: Both the gene for nitric oxide synthase (NOS) and a corresponding pseudogen are transcribed in the neurons of a water snail . The pseudogene RNA inhibits the translation of the correct NOS RNA.
- Example 2: Developmental disorders in mice could be traced back to a regulatory gene called Makorin1. Somehow this gene was disturbed. However, no mutations were found in the base sequence of this gene. Instead, a change was found in a pseudogene. If this pseudogene was destroyed experimentally, the real gene could no longer function either.
Today we know more than 20 such pseudogenes that are regulating. However, it seems questionable whether these pseudogenes had such a regulating function from the start.
Reactivation of pseudogenes
There also appears to have been cases in evolution where useless pseudogenes became functioning genes again. Individual differences are also possible. In certain people an olfactory receptor pseudogene has no function, in other people it is transcribed and even translated. In the case of maize, reactivation of pseudogenes seems to occur particularly frequently when the plants are exposed to stressful environmental conditions. Seen in this way, pseudogenes can not only be viewed as dead genes, but also as sources for new genes.
literature
- The Real Life of Pseudogenes . In: Scientific American, August 2006
- A coding-independent function of gene and pseudogene mRNAs regulates tumor biology . In: Nature, Vol. 465, pages 1033-1040, June 24, 2010
See also
Individual evidence
- ↑ Thierry Heidmann, Cécile Esnault, Joël Maestre: Human LINE retrotransposons generate processed pseudogenes . In: Nature Genetics . 24, No. 4, 2000, ISSN 1061-4036 , pp. 363-367. doi : 10.1038 / 74184 .