Something is antithetical when it is in complete and utter opposition to the character of something.

Analysis of protein-coding genetic variation in 60,706 humans

reported as: Largest collection of human exome sequence data yields unprecedented tool for diagnosing rare disease

…variation that was expected, but not found, in the data offered new insight. Some genes were found to have less than the expected number of missense mutations, which change the protein sequence, or “loss-of-function” mutations, which obliterate protein function. With such a large sample size, the researchers were able to quantify the deficit of these types of mutation per gene, identifying a few thousand “highly constrained” genes for which natural selection has weeded out these mutations because their effects are so detrimental.

Masatoshi Nei (2013) reached an anthetical conclusion: “…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world. In this view of evolution there is no need of considering teleological elements (p. 199).”
The data show that without the biophysical constraints that link hydrogen-atom transfer in DNA base pairs in solution from energy-dependent changes in microRNA flanking sequences to codon usage and protein folding chemistry, theorists cannot link RNA-mediated amino acid substitutions to DNA repair and all extant biodiversity, life on Earth. The number of mutations is too great, and they have been linked from virus-driven energy theft to pathology.
No beneficial mutation has been linked to evolution of one species from another. RNA-mediated amino acid substitution have been linked to all biodiversity via the innate immune system and supercoiled DNA, which link energy-dependent changes in angstroms to ecosystems in all living genera. See also:

Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors (2012) and Nutrient-dependent/pheromone-controlled adaptive evolution: a model (2013)

Unconscious affects that are manifested during the development of diversified life and human behavior are, by their very nature, part of life that few people think about (Kohl et al., 2001). Therefore, the largest contributor to the development of our personal preferences may be the unconscious epigenetic effects of food odors and pheromones on hormones that organize and activate behavior. If so, the model represented here is consistent with what is known about the epigenetic effects of ecologically important nutrients and pheromones on the adaptively evolved behavior of species from microbes to man. Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific ‘fit’.

Since the day my 2013 review was published, which was on the same day “Mutation-driven evolution” was published, nothing published by serious scientists has supported the claims of Masatoshi Nei, or other theorists. See for comparison:

Experience-Dependent Plasticity Drives Individual Differences in Pheromone-Sensing Neurons (2016)

 •Individual differences in cell types are not random
•Sex differences in pheromone-sensing neurons are controlled by experience
•Changes in specific cell types are governed via “use it and lose it” plasticity
•Targeting plasticity to specific cell types changes animal behavior

Protein Folding

Protein folding is the physical process by which a protein chain acquires its native 3-dimensional structure, a conformation that is usually biologically functional, in an expeditious and reproducible manner. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil. Each protein exists as an unfolded polypeptide or random coil when translated from a sequence of mRNA to a linear chain of amino acids. This polypeptide lacks any stable (long-lasting) three-dimensional structure. Amino acids interact with each other to produce a well-defined three-dimensional structure, the folded protein is known as the native state. The resulting three-dimensional structure is determined by the amino acid sequence.

Inching toward the 3D genome

Re: “…the nucleome structure changes as cells age, differentiate, and divide, and researchers want to understand how and why.”

Cell type differentiation is nutrient-dependent. RNA-directed DNA methylation links RNA-mediated amino acid substitutions to cell type differentiation via protein folding during life history transitions. Amino acid substitutions stabilize protein folding; mutations perturb it, during nutrient-dependent theromodynamic cycles of protein biosynthesis and degradation.

Life is physics and chemistry and communication —

The metabolism of nutrients links metabolic networks to genetic networks via species-specific pheromones that control the physiology of reproduction. Simply put, pheromones link nutrient-dependent life via physics, chemistry, and the conserved molecular mechanisms of communication in species from microbes to man.

Until nutrient-dependent protein folding is linked via the conserved molecular mechanisms of amino acid substitutions and pheromone-controlled DNA stability in organized genomes, which links the epigenetic landscape to the physical landscape of DNA, researchers must take a piece-meal approach to integrating the requirements for life and successful life history transitions — despite the fact that life history transitions have been detailed in the context of the honeybee model organism. See: Honey bees as a model for understanding mechanisms of life history transitions

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