How Heredity Works

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    So how does DNA produce a living organism? Primarily it guides the production of proteins. In the half century after Franklin, Gosling, Watson, and Crick worked out the double-helical structure of DNA, molecular biologists have worked out how that double helix gets used in the cell to make the building blocks of life. They have discovered that DNA has three basic components Ė genes, switches, and controllers. Genes produce RNA that produces proteins and other molecules for the cell. Switches turn genes on and off. And controllers flip the switches, presumably in response to chemicals or other environmental factors.

    The process starts when a chromosome partly unravels and the DNA at least partly unwinds and its halves separate to expose the gene that they encode at a particular location. Bits of ribose bearing the genetic bases (adenine [A], cytosine [C], guanine [G], and uracil [U]) come to the exposed parts and attach to their complements (thymine [T], guanine, cytosine, and adenine, respectively). The bits of ribose then stick to each other to form a string of codons (trios of bases) that biologists call messenger RNA (mRNA). The messenger RNA separates from the DNA and floats out into the cellular cytoplasm until it meets a ribosome, which grabs onto one end and begins the process of reading out the instructions encoded in the mRNA.

    The ribosome acts by drawing in little wads of RNA called transfer RNA (tRNA). Each of those wads has a single anti-codon at one end and a corresponding amino acid molecule loosely attached at the other end. If a tRNAís anti-codon matches the codon that the ribosome has grabbed on the mRNA, then the ribosome pulls it in, brings the codon and the anti-codon together, and adds the amino acid to the protein under assembly in the ribosomeís grasp. The ribosome then discards the tRNA and moves on to the next codon on the mRNA.

    Sixty-four possible codons provide the means of bringing twenty different amino acids together and of signaling the ribosome to stop adding amino acids to a particular protein (the codons UGA, UAA, and UAG serve as stop signals). That redundancy might, on first impression, seem to have no effect upon the production of proteins: indeed, biologists call the mutations that replace one codon with another that specifies the same amino acid "silent mutations". But, in fact, which coding for a particular amino acid the mRNA uses affects the speed at which the ribosome adds that amino acid to the growing protein. Further, the mRNA strands have a tendency to knot themselves up and how tightly a given strand knots up can affect the rate at which the protein it encodes gets produced. Thus we can have two mRNA strands that encode the same sequence of amino acids, but one will yield the product faster than the other because the ribosome can unknot it and read it faster.

    Molecular biologists have found another way in which silent mutations can have profound effects on an organism. In bacteria the genes exist as uninterrupted lengths of DNA that float freely within the organism, so the protein producing process can proceed in a straightforward way. In eukaryotes, though, the genes, which remain trapped within a cell nucleus, consist of alternating segments of DNA called exons (which encode the production of proteins) and introns (which do not encode the production of proteins). In human DNA the exons have, on average, 150 bases, while the introns have, on average, 3500 bases and can have as many as half a million or more. Both exons and introns get copied into mRNA, so something in the cell must cut out the introns and splice the exons together before a ribosome can use the mRNA to produce a protein. To aid in that effort both exons and introns have cut-and-splice-here codes at their ends. A silent mutation in one of those codes would change the proteins that the gene encodes.

    But if all cells have the same DNA and thus produce the same proteins in the same proportions and amounts, then how can any living thing grow into anything but an undifferentiated blob?

    Clearly DNA does not always produce the same proteins in the same proportions and amounts; instead, the quantities of various proteins that a given strand of DNA produces depend upon where in the organism that strand floats. As DNA gets tightened or loosened by external forces, it produces different amounts of various proteins. The pattern of protein production determines what proteins are available to the cell to build and rebuild itself. The interaction between an organism and its environment determines the shape the organism acquires as it grows. Experiments have shown that forces exerted on cells, along with a pair of proteins called YAP/TAZ, control how the DNA in the cellís nucleus produces proteins for cell growth (see "Twists of Fate" in the October 2014 issue of Scientific American).

    Over the longer part of an eon the interplay between mutation and natural selection has shaped the relationship between the forces acting on a cell and the cellís response in producing a certain kind of tissue. Mechanical stresses exerted upon the cell, reflecting the stiffness of surrounding material, push and pull the cellís internal parts in ways that affect its chemical behavior. Those strains determine whether the cell will become part of a bone, part of a muscle, or part of a nerve.

    Multicellularity began with identical cells sticking to each other in flat sheets. Some of the sheets formed hollow spheres, such as we see manifested in Volvox. Under the influence of pushes and pulls from their environment some spheres became misshapen and their cells, by pulling on their neighbors, gave the organism a certain small ability of movement. Life produced creatures such as we see manifested in Hydra. Subject to the ruthless and relentless breeding program of natural selection, DNA that gave its manifestation the shape and movements that best fit its environment reproduced itself preferentially over less successful DNA and thus came to dominate the population of organisms it encoded.

    Subsequent mutations were then selected or deleted from existence by the inexorable logic of evolution. DNA changed in such a way that gave its cells a structure that would respond to the appropriate mechanical and/or chemical stress by differentiating from the original cells. From the basic bacteria-like cells forming a single-layer skin around an empty space a few surrounding a hole in that skin can expand or contract in response to the presence of nutrients, thereby making the hole grow larger and smaller as a primordial mouth. Cells that expand and contract in response to external stimuli will evolve into muscle tissue. Cells that evolve especially stiff cell walls become wood or cartilage, the foundation of bone. And cells that respond to certain stimuli by propagating chemical waves along their lengths, in a kind of salt-exchange shrug, evolve into neurons, the cells that comprise nerves.

    As an organism progresses from fertilized egg or seed, it faintly recapitulates the evolution of life, from ball of cells to fully differentiated organism: the history of life plays out in abridged form. We catch a glimpse at how life acquired its various features as mechanical and chemical stresses push and pull differentiated organs into existence. The egg, the womb, and the seed have evolved to provide the right environment in which a single cell can grow into an elaborately manifested organism. This is how heredity works.


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