Buffering the cell against gene alterations

These protection systems are effective, but they are not perfect. The threat of DNA damage remains; sustained attrition cannot be resisted altogether. So far as we know, organisms have been susceptible to such assaults throughout the history of life, perhaps more intensely in some eras than others, and not all organisms are equally well defended. Therefore, DNA has always been susceptible to mutation. A mutation might involve the insertion, deletion or alteration of a single base (a point mutation), or it might affect more of the DNA sequence.

Although a mutation is usually not good news for the cell or the organism, it might not always be bad news; many mutations have no discernible consequences. One reason is that in most eukaryotes (though not in prokaryotes), a good deal of the DNA is "junk". That is to say, it does not encode proteins. In human DNA, for example, genes make up only 3-5% of the total. The more non-coding DNA there is, the lower the chance that a mutagen will affect a gene. Suppose you are in a crowd where someone starts shooting at random. The bigger the crowd, the smaller your personal risk of being hit; there is safety in numbers.

Moreover, a mutation that does occur within a gene might not alter the protein encoded in that gene. The genetic code contains redundancies, so a change in a DNA letter might not change the protein's amino acid sequence. Also, if an amino acid is changed, it might be replaced with one that serves equally well, and the protein's function remains unimpaired. For example, the DNA base sequence UUU specifies the amino acid lysine. That is to say, where UUU occurs in the gene, lysine will occur at the corresponding point in the protein. UUC also specifies lysine, so a mutation that converted the third U to C would not alter the protein at all; lysine would still appear in the same place. UCU specifies a different amino acid, arginine (so does UCC), so if the second U were mutated to C, the protein would be changed. But arginine and lysine are chemically similar in many ways, so the replacement of one of these amino acids by the other might still leave the protein functional, though slightly changed.

There is another and rather simpler point. In sexually reproducing organisms, each cell has two copies of nearly every gene, one copy from each parent. If one of these copies is defective, the other will probably be normal. So a mutation in one copy of a gene still leaves the organism capable of making the normal protein. This is why the "carriers" of genetic diseases are often free of symptoms: they have one mutant gene and one normal one. Only those offspring who have mutations in both copies of the gene are affected.

The loss of one gene might make the cell non-viable, but the consequences are seldom so extreme. In these days of advanced molecular biology, it is easy to eliminate almost any gene from an embryo, and in most cases the organism develops more or less normally. "Gene knock-out" has become a routine experimental technique. Many different genes can be knocked out of a mouse without it ceasing to be a viable mouse. Of course there are exceptions, where the alteration or loss of a single gene produces a seriously impaired or completely non-viable cell or organism, but despite the number of genetic diseases listed in our medical text books, not all genes seem to be "essential".

This is not really surprising. As we said in chapter 9, complex systems with redundancy are robust; they can function when individual components are missing. So we ought to expect cells to tolerate a certain amount of gene damage or loss; the rest of the system compensates for their absence or malfunction. The defective cell might lack some structure or activity that the normal ("wild-type") cell has, but in most respects it will be the same cell. Relatively few gene products are so essential for the cell's viability that the system cannot compensate for their absence.

In summary, organisms are buffered against mutations by:-

  • quot;junk" DNA;
  • the redundancy of the genetic code;
  • the chemical similarities between some pairs of amino acids;
  • in sexually reproducing organisms, two copies of nearly every gene;
  • compensation for the effects of gene loss by the rest of the system (a complex system made robust by redundancy).

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