Epigenetic regulation of alternative splicing
https://science-explained.com/theory/one-gene-many-proteins-alternative-splicing/Excerpt: "Just as it is possible to make different dishes by using some ingredients but leaving out others, it is also possible to make different proteins by including or leaving out certain “ingredients” of genes. This process is called alternative splicing and it makes it possible to produce different proteins from the same gene (these different protein versions from the same gene are called isoforms). In this way, our bodies can produce over 100.000 proteins from only 20.000 genes." (My add: Probably millions of different proteins according to latest research.)
"But what about alternative splicing? The principle is the same, a pre-mRNA is produced and spliced, a 5’ cap is added and a poly-A tail is added. The only difference is, that instead of just splicing the introns out, some exons might be spliced out too. This leads to different proteins, one in which all 3 exons are used and one in which only exon 1 and 3 are used. So one gene for two proteins (see figure below).
The example discussed here concerns a gene with only 3 exons. Although this keeps the explanation simple, it does not provide the potential of many different isoforms. If we would have more exons that would mean more flexibility in the number of proteins that can be formed from a single gene. The gene Dscam from the fruitfly (Drosophila melanogaster) has 95 exons and can form 38.016 different proteins. So this one fly gene can form more different proteins than the number of genes we humans have in total!
All in all, alternative splicing is an essential part of complex animals like us. The use of alternative splicing makes it possible to have many different proteins to fulfil all the different tasks necessary in our lives without the need of a gigantic genome."
Alternative splicing (AS) is regulated by epigenetic mechanisms:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325479/
"Generally, AS can be coupled with transcription and subjected to epigenetic regulation, such as DNA methylation and histone modifications. In addition, ncRNAs, especially long noncoding RNAs (lncRNAs), can be generated from AS and function as splicing factors (“interactors” or “hijackers”) in AS."
My comment: Differences in the DNA are not the reason for human phenotypic variation. Genetically identical twins might have different colours of skin, hair and eyes. The most significant reason for variation in organismal characteristics can be found in epigenetic mechanisms and factors that regulate and mediate the alternative splicing mechanism. We should remember that genetically (DNA) all people are 99.9 % similar. The 0.1% difference is strongly related to hereditary diseases. This is why evolution believers hardly find fully beneficial DNA mutations. Evolution has no mechanism. Don't get lost.
