The Century of the Gene, E. F. Keller, 2000.
Evelyn Fox Keller, discusses the
rediscovery of inheritance and the meaning of genes.
By doing so she uncovers the limits of metaphors; her introduction
to life’s complexity becomes an adventure in discovering the miracle of
the structural and functional units of adaptation, immune response, memory,
and replication of variability.
The challenges of consensus & discovery 
There is a paradox in that as DNA/RNA discoveries reveal an ever greater complexity; the widespread public beliefs in “genetic determinism” are growing ever more simplistic.
This means that there is a pervasive and popular belief in the dominance of nature, meaning genes determining an organism's "fate" or people's characters, despite the near absence of supporting evidence for the nature side of the "nature vs. nurture" argument.
page 5.
This widespread scientific agreement was that by reducing a set of complex processes to its component parts researchers would reveal greater clarity and discover underlying causes for the way the parts function as they contribute to an integral whole. Simplicity of form and function was supposed to emerge as one moved from the cellular to the chromosomal level.
Discovery:
After 1953 and 1954, though there were skeptics before the deciphering of the double helix, further discoveries about proteins, ribonucleic acid (RNA) and cellular functions undermined the "reductionist" approach around which two beliefs were central to the consensus in microbiology:
The scientific consensus began to unravel quickly after the discovery of the structure of DNA. The consequence of this unraveling consensus was that the simplicity of the cell was shattered, the role of RNA in altering DNA in retroviruses such as leukemia and acquired immune deficiency syndrome (AIDS) helped dismantle a reductionist approach, and eventually the gene, as a concept, emerged as both a decoding process and a cluster of protein mediated responses to changing cellular conditions.
1859, Darwin's Origin of Species
1900, papers on “the rules of inheritance” DeVries, “pangens”
1906, genetics announced by Bateson (Wm.)
1909, genes suggested as a clarifying word
1944, Schroedinger's question asked: What is life?1953, Franklin, Wilkins, Watson, and Crick devise molecular DNA model.
Keller's key points in the argument
that genes are not just codes for genotypes & expressions of selected for
phenotypes
1. The inadequacy of DNA as an explanation for inheritance and natural selection
2. the collaboration of proteins during DNA replication for effective mitosis.
3. “high fidelity" of genotype transcription.4. the four functional factors proteins perform & SOS system which:
a. allows replication to proceed,
b. generates diversity for its own sake (adaptability under stress?).
5. preservation of “evolvability,” evolution as fortunate paring down.
6. individuality, multicellularity and sex arise from a synthesis of
a. nucleic acid integrity and amino acid fidelity,
b. metabolic system for self-maintenance.
Barbara McKlintock’s description of the genome as an exquisite organ
“ a highly sensitive organ of the cell monitoring genomic activities and correcting common errors, sensing the unusual and unexpected events, and responding to them.”Page 33.
“The Meaning of Gene Function: What does a gene do?”
“But what does a gene do?” “What in fact is a gene?”
Particulate materiality (Genotype)
Simultaneously animating and directing the cell’s construction
Do genes act as “the cell’s brain” as Erwin Schroedinger suggested, or
- structure of proteins
- hereditary material for natural selection to act upon?
47
How is elementary life an oxymoron?
Because single-celled life is more complicated than we may be able to imagine.
48
DNA, molecules or structure of the nitrogen base pairs of the double helix.
How could the structure of the gene be translated into the function of the gene?
“they needed to explain how it is that the unit of hereditary, as de Vries had earlier put it, ‘impresses its character upon the cell’.”49
Genes as conceived by 20th century scientists have a dual responsibility:
A. Preserve genetic memory through the generations (fidelity),
B. In each generation to steer the course of individual development (adaptability).
Regulator genes
Central dogma DNA ‡ RNA ‡ Endoplasmic Reticulum for protein building
Operon model for gene regulation
Splicing and editing mechanisms
Four possible means for generating variability by operon splicing
“I have been using the term gene to refer to the original stretch of DNA.
But doing so means that we have to give up on the notion, even for structural
genes, that one gene makes one enzyme (or protein). One gene can be employed
to make many different proteins….Which protein should the gene make, and
under what circumstances? And how does it choose?”
“Responsibility for this decision lies elsewhere, in the complex regulatory
dynamics of the cell as a whole.”
63
Ribonucleic acid, the replicating molecule may be older in origin than DNA
Concerning the role of m-RNA (messenger RNA transcript [of the DNA] )
“the players rewrite the score in their very execution of it.”
That is, protein construction by RNA can alter, control, influence, or suppress the expression (phentotype) of the base pair sequences (genotype).
Protein synthesis occurs in four steps
A. transcription (Marian)
B. splicing and editing
C. ribosome assembly of amino acids
D. translation into the into protein (Polypeptide) chain
Hemoglobin protein carries oxygen (chelated iron molecule in a porphyrin ring.
Proteins too have their regulatory sites…[and] changes in the three dimensional
structure of a protein…at these sites; in turn, change in conformation
alters the function and activity of the protein.”
64.
Thus: “one protein -- many functions.”
“But there is no single fact of the matter about what the gene is.”
66.
“Unlike chromosomes, genes are not physical objects but are merely concepts
that have acquired a great deal of” implicit assumptions and un-testable
attributes.
67
Thus the gene as an insufficient description of what the process of inheritance
involves, gave way to the concept of a “mediated” process or a “genetic
program.”
“The gene as two very different kinds of entities:
one,
a structural entity—maintained by the molecular machinery of the cell so that it can be faithfully transmitted from generation to generation,
and
the other,
a functional entity that emerges only out of the dynamic interaction between and among a great many players,…”
p. 71.
Structural sequences (nitrogen base pairs that constitute DNA and RNA forms) -- called base pair sequences, BPS.
Exons and introns that specify code stretches or operons of DNA to select for amino acids.
Prions, stretches of nucleic acid that “jump” or move within the genome.
Proteins (which themselves are made from mRNA transcriptions of DNA).
Ribosomes (where amino acid chains are cobbled into polypeptide [protein] chains.Junk DNA (like spare parts) comprised of non-coding stretches of nitrogen bases.
Chromosomes are physical structures where the genome is “quartered” or housed in discrete units or twisted bundles; traits are attributed to certain loci on specific C-somes, or chromosomes.
“This is the picture of life:….
We know that all cells contain the directions for all cell life, written in the DNA of their chromosomes, and that these directions include specification of how to make the many kinds of enzyme molecules by means of which the cell converts available substances into metabolites suitable for the making of more cells.”
James Bonner, 1965,
p. 73.
can the concept of a “genetic program…be said to explain development?”
“How can an organism be built out of the mere accumulation of different
proteins?”
p. 74.
Ernst Mayr’s critique of “bean-bag” genetics not taking account of gene interactions
p. 76.
“…any one cell represents more an historical than a physical event….No,
any living cell carries with it the experiences of a billion years of experimentation
by its ancestors. You cannot expect to explain so wise an old bird in a few
simple words."
Max Delbrück, 1949,
p. 103.
“But if contingency is the key to evolution, it might be argued that the obverse of contingency—the capacity to stay on track, despite the myriad vicissitudes that invariably plague a developing organism, is the key to biological development.”
p. 104.
Lesson:
The idea that genes are an unmediated entity with a one to one relationship to traits (phenotype, or expressed observed characteristics of an organism) is a resilient prejudice.
The public, based on historical conditioning since the middle ages, believes that we are what we are due to our genetic endowment. The widespread belief that inheritance is the primary determinant in behavior persists in shaping public opinions.
Thus some serious divergence has emerged:
Wilson: the cell is most like a rain forest in its complexity of functional parts.
Wes Jackson: the genome is most like an ecosystem with complex levels.
Genome as an integrated system?
Geno-system, as a combination of genome and ecosystem in order to convey the probable complexity or scale of details involved in what have simply been called genes.
Recall that 30,000 genes or more are at work in making, maintaining and reproducing a human being. In addition to DNA, RNA and proteins make up the functional parts of the genome that is more than a collection of genes.
It is more of an operational center for the construction of proteins that regulate all phases of an organism's response to its surroundings. Comparable to the many levels of feedback that operate in an ecosystem the genome is a collection of feedback mechanisms that regulate the levels of proteins, enzymes and hormones needed by any living being.
A crucial paradox persists between the recent genomic discoveries and the widespread public misunderstanding of genetic science.
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