Consider for example de novo genes (e.g., [ 9- 13])—genes that presumably have arisen "out of thin air" by a sequence of random mutations that came together into a new functioning gene, including signals for transcription and translation and even alternative splicing [ 11].
ALS patients with a TARDBP mutation that come to autopsy show ALS-TDP pathology that is indistinguishable from the TDP-43 pathology observed in sporadic ALS (152 156).
From the perspective of the theory proposed here, many different observations fall into place as pieces of one puzzle, including transcriptional promiscuity, molecular parallelism, the nonrandomness of mutation that comes out very clearly from the empirical evidence, and much more, as already stated in the above comments and in the paper.
Hereditary cancer comes up from mutations that occur in high-penetrant predisposing tumor genes.
"Unlike infectious diseases, for example, which we treat by killing the disease-causing agent, in the case of diseases that come from mutations in our own genes, one has to go into the cells and do surgery on our genomes to fix the root cause.
Most of the mutations may be uninformative "passengers" that come along for the ride, whereas many might be "drivers" that actually cause the unregulated cell proliferation that defines cancer.
To understand why HGT can prevent Muller's ratchet despite its average deleterious effect due to the high mutation load of eDNA that comes from dead cells, we considered the following simple Wright-Fisher model.
Since multiple "hits" are thought to be required for malignant transformation [ 67], it might be advantageous for a tissue to minimize the number of cells that carry two or more mutations [ 11, 68], even if that came at the cost of an overall increase in mutation frequency.
DNA markers are genetic markers that came from various classes of DNA mutations and rearrangements (Collard et al. 2005).
One that came up a bunch yesterday is the population mutation rate or the population scale mutation rate 4Nmu.
