Paralogs are homologous genes that arose through gene duplication. In humans and other species, gene duplication events are food energy-dependent. They result in two copies of a gene within the same genome. Sometimes, one or both of the duplicates is altered by the virus-driven degradation of messenger RNA, which causes the creation of toxic peptides in gut microbes that link mutations to all pathology.
From the Introduction:
Defective completion of the PTC [petidyltransferace center] causes developmental disorders associated with an increased propensity for malignant transformation. Hence, our atomic models not only illuminate the mechanism of PTC assembly but also suggest how mutations found in leukaemia disrupt this process.
My comment: This is of interest to me in the context of energy-dependent autophagy, see also:
The identification of a crosslink between the N-terminus of Lsg1 and the P-site loop of uL16 (Figure 1—figure supplement 5A,B and Supplementary file 2) raises the intriguing possibility that Lsg1 may proofread accommodation of the uL16 P-site loop into the PTC as the Nmd3 β4–5 loop is retracted. In this model, Lsg1 may act as a gatekeeper that licenses further progression of 60S subunit maturation by dissociating only once it senses that uL16 is correctly integrated. The disengagement of Lsg1 from the N-terminus of Nmd3 will further destabilise the interaction of Nmd3 with the 60S subunit, allowing retraction of the L1 stalk to pull Nmd3 completely off the intersubunit face.
It is the most confusing way I have seen to say that PTC assembly is a light-activated gate-keeper of biophysically constrained viral latency.
In conclusion, we have used single-particle cryo-EM to demonstrate the conformational changes during cytoplasmic 60S subunit maturation that couple incorporation of the ribosomal proteins eL40 and uL16 to the release of Nmd3 in what is likely to be a universal mechanism in eukaryotes. Our data not only reveal how the central functional site of the ribosome is assembled, but provide a framework to interpret the consequences of mutations linked to leukaemia-associated ribosomopathies.
My summary: Used of single-particle cryo-EM technology allowed others to reveal the fact that the virus-driven theft of the sun’s anti-entropic virucidal energy links changes in the light-activated assembly of the microRNA-RNA-peptide nanocomplex to the creation of toxic peptides. The creation of toxic peptide link mutations to all pathology.
But some researchers from some countries claim that mutations are responsible for the evolution of differences in all species on Earth. For country-wide exceptions see:
microRNA Israel >800
microRNA Iran >1200
microRNA Korea > 1900
Researchers from these three countries are more likely to approach the energy-dependent survival of all species on Earth to feedback loops that link the sun’s anti-entropic virucidal energy to biophysically constrained viral latency via The roles of microRNAs in regulation of autophagy during bacterial infection 7/24/19
…we are only just beginning to understand the role miRNAs play in autophagy processes and how it affects the outcome of host-pathogen interactions in various bacterial infections. In this review, we focus on how Mycobacteria, Listeria, and Helicobacter evade host protective immune responses using miRNA-dependent mechanisms to suppress autophagy.
Many researchers from countries that share aspects of the so-called Abrahamic faiths, relating specifically to the Biblical patriarch Abraham, start with God’s Creation of sunlight and water and base their claims about species diversity on the likelihood that microRNAs are the endogenous substrates found in all cell types of all living genera. If true, in the Biblical sense, there should be experimental evidence to support their claims.
…plants alter microRNA (miRNA) biogenesis in response to light transition.
If light-activated changes in microRNA biogenesis do not biophysically constrain autophagy during bacterial infection, this additional evidence of top-down energy-dependent cause and effect is not likely to be linked from the physiology of reproduction to disease prevention in all species on Earth.
But see also: MicroRNA in Innate Immunity and Autophagy during Mycobacterial Infection (10/29/16)
…we present a comprehensive review of the recent literature regarding miRNA profiling in tuberculosis and the roles of miRNAs in modulating innate immune responses and autophagy defenses against mycobacterial infections.
Future studies revealing the functions of host miRNAs that regulate autophagy and immune responses could contribute to the development of miRNA‐based approaches for host‐directed therapeutics/vaccines against mycobacterial infections.
See for comparison: Nutrient-dependent/pheromone-controlled adaptive evolution: a model (6/14/13)
…evidence links olfactory/pheromonal input to genetically predisposed species-specific behavior via previously unmodeled epistatic interactions that must occur throughout the lifecycle transitions of all organisms. Thus, the epigenetic ‘tweaking’ of the immense gene networks that occurs via exposure to nutrient chemicals and pheromones can now be modeled in the context of the microRNA/messenger RNA balance, receptor-mediated intracellular signaling, and the stochastic gene expression required for nutrient-dependent pheromone-controlled adaptive evolution. The role of the microRNA/messenger RNA balance (Breen, Kemena, Vlasov, Notredame, & Kondrashov, 2012; Duvarci, Nader, & LeDoux, 2008; Griggs et al., 2013; Monahan & Lomvardas, 2012) in adaptive evolution will certainly be discussed in published works that will follow.
MicroRNAs and bacterial infection (6/25/13)
And see: Autophagy.pro
“Transmissible cancer really blurs the lines between infection, infestation, metastasis, but evolution doesn’t care about classifications. It’s just whatever works. And spreading cells from one animal to another works.”
It does not work in the context of how virucidal sunlight is linked from Pseudomonas fluorescens to plant growth and via biophysically constrained viral latency.