Thursday, June 02, 2016

genes without prominence...,


inference-review |  The cell is a complex dynamic system in which macromolecules such as DNA and the various proteins interact within a free energy flux provided by nutrients. Its phenotypes can be represented by quasi-stable attractors embedded in a multi-dimensional state space whose dimensions are defined by the activities of the cell’s constituent proteins.1
 
This is the basis for the dynamical model of the cell.

The current molecular genetic or machine model of the cell, on the other hand, is predicated on the work of Gregor Mendel and Charles Darwin. Mendel framed the laws of inheritance on the basis of his experimental work on pea plants. The first law states that inheritance is a discrete and not a blending process: crossing purple and white flowered varieties produces some offspring with white and some with purple flowers, but generally not intermediately colored offspring.2 Mendel concluded that whatever was inherited had a material or particulate nature; it could be segregated.3

According to the machine cell model, those particles are genes or sequences of nucleobases in the genomic DNA. They constitute Mendel’s units of inheritance. Gene sequences are transcribed, via messenger RNA, to proteins, which are folded linear strings of amino acids called peptides. The interactions between proteins are responsible for phenotypic traits. This assumption relies on two general principles affirmed by Francis Crick in 1958, namely the sequence hypothesis and the central dogma.4 The sequence hypothesis asserts that the sequence of bases in the genomic DNA determines the sequence of amino acids in the peptide and the three-dimensional structure of the folded peptide. The central dogma states that the sequence hypothesis represents a flow of information from DNA to the proteins and rules out a flow in reverse.

In 1961, the American biologist Christian Anfinsen demonstrated that when the enzyme ribonuclease was denatured, it lost its activity, but regained it on re-naturing. Anfinsen concluded from the kinetics of re-naturation that the amino acid sequence of the peptide determined how the peptide folded.5 He did not cite Crick’s 1958 paper or the sequence hypothesis, although he had apparently read the first and confirmed the second.

The central dogma and the sequence hypothesis proved to be wonderful heuristic tools with which to conduct bench work in molecular biology.

The machine model recognizes cells to be highly regulated entities; genes are responsible for that regulation through gene regulatory networks (GRNs).6 Gene sequences provide all the information needed to build and regulate the cell.

Both a naturalist and an experimentalist, Darwin observed that breeding populations exhibit natural variations. Limited resources mean a struggle for existence. Individuals become better and better adapted to their environments. This process is responsible for both small adaptive improvements and dramatic changes. Darwin insisted evolution was, in both cases, gradual, and predicted that intermediate forms between species should be found both in the fossil record and in existing populations. Today, these ideas are part of the modern evolutionary synthesis, a term coined by Julian Huxley in 1942.7 Like the central dogma, it has been subject to controversy, despite its early designation as the set of principles under which all of biology is conducted.8

The modern synthesis, we now understand, does not explain trans-generational epigenetic inheritance, consciousness, and niche construction.9 It is possible that the concept of the gene and the claim that evolution depends on genetic diversity may both need to be modified or replaced.

This essay is a step towards describing biology as a science founded on the laws of physics. It is a step in the right direction.