Genetics as it applies to evolution, molecular biology, and medical aspects.
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Okay the other day in my genetics class we went over basically how there are alot of repeat sequences everywhere in the genome, even introns. Examples we talked about were microsatellites (dispersed everywhere which are short sequences), dna transposons such as SINES and LINES, alpha satellite repeats in centromeres, telomerase repeats at the end of chromosomes, and some others. I know that sometimes LINES can use reverse transcriptase to insert a mRNA back into DNA and cause diseases but nowhere in my book did it mention what would happen if a repeat sequence would be put into an exon. My theory would be that if inserted into the exon the repeat sequence would cause a frameshift mutation and cause problems with the splicing and the proteins made would be incorrect. The repeated sequence would not code for proteins so would the ribosome just skip over this during translation? Is this the major reason why or is there a bigger reason that I am missing. Thanks for any guidance!
the inserted mRNA is long (at least several hundreds of bases), thus the insertion doesn't cause frame shift, but gene knock-out, since the cell is not able to translate it correctly.
Cis or trans? That's what matters.
okay, well this is a really good question at last.
one of the greatest theories in genetics is the origin of introns in eukaryotic DNA. They may have multiple origins. My favored idea, and it is the only sensible one I have heard, apart from the one I came up with on a previous post but have only just come to appreciate in answering this question, is that these retroelements (themselves derived from retroviruses and/or the founders of retroviruses) jumped in to the genome, and interuppted the genes. The cells which survived had to learn to unsplice these viruses, but rather than doing it at the genome level, it was done at the transcriptome level (mRNA). This had advantages as well as the obvious disadvantages, hence evolution took its course.
Don't forget the introns are the bits that end up on the cutting room floor, in mRNA terms.
Dude, its sooo much more likely that the mRNA so retrotransposed would lead to the creation of an extra locus for the gene of interest.....remember its very unlikely to hit a piece of protein coding DNA, due to the fact that introns are way way way bigger than exons - 10-100x bigger at least in most cases i estimate. In fact there are pseudogenes in the human genome which are very strong evidence of this type of evolution.
http://ukpmc.ac.uk/abstract/MED/8111117 ... C365C5C17E
well, that would cause disease!
that is the 67% probability for sure.
most likely event is the gene would be a mutant phenotype- either a 'genetic knockout' or it may function as a wrong-un; probably would take some getting used to depends on the gene, the exon (a lot of coded DNA has redundant function - an argument in favour of evolution being more like a river finding its way to the sea than directed by an engineer or a God, although correction of deleterious mutations like this may be done by a God, I am not sure of the evidence yet) hence if it goes in in the correct frame, then it may not cause any problems (hypothetically, at least).
it might code for viral proteins, or gobbledeegook polypeptides. In fact you should have been told that these transposons often encode their own enzymes such as reverse transcription polymerase, although such proteins-coding sequences are often a mess due to mutations - for jumping the gene only needs to have jumping signals to jump - the transposase can be provided by say a viral infection or another transposon which ironically may have mutations in its jump-signal DNA which mean it CANT jump!
Once the transposon is in the genes exon, well the other answers cover it I think .
BUT ... in case not: the ribosome would try to read it - it would NOT just skip over it! if it was at the first exon, it might take over entirely with the first start codon, or its rival start codon might compete for the ribosome thus decreasing protein production. If it had stops (stop codons) , then that would be the end of the protein synthesis at that first stop codon, unless amber/opal/ochre tRNA's are considered (phew!), or unlikely editing by APOBEC family...(!). If it had no stop codons whatsoever (very unlikely), then a readthru into the 'real' exons of the gene would ensue, and function ...who knows the impact. As for transposon proteins, if they are still intact, then there would be a 1/3 chance of a correct reading frame x1/2 chance that it was in the right direction multiplied by the number of encoded proteins in the transposon - If you consider that a retrovirus from which they evolved has many protein-coding sequences (like HIV... env gag nef pol rev tat vif vpr vpu 9 protein coding genes producing >9 proteins via alternative splicing). So one could anticipate that such transposon (broken viral) genes would be incorporated quite often when exons are hit, which as i say is rare, but remember there are some 1-100x10^12 cells per human body! So rare events happen in you probably every day, at a wild guess. What is important is to have a healthy immune system which will kill off these cells, before they become transformed into cancer cells, which is the usual outcome of a new uncontrolled protein. And remember, as each such creation is novel, and made by your'self', the difficult question is how the immune-system can tell which is which.
As a vision, one could see a rare transposon jumping into an active gene, and hijacking its machinery, making its own transposases in enormous amounts, and this causing cancer as the entire genome is blitzkreiged by genes leaping in and out at random. The immune system would be overrun. Evolution pressure by a single gene. Amazing.
Incidentally, you may have heard of RAG1 and RAG2, which splice genomic DNA to make the T cell receptors and B cell receptors. They evolved from such transposases, when we were all jawless hagfish-like.
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