Mutation


Mutations are alterations of genetic material.  They occur frequently during DNA duplication in cell division.  This should not be surprising considering the fact that mitosis and meiosis are essentially mechanical processes with many complex operations that must be precisely completed in order for duplicate DNA molecules to be created.  There are four common categories of mutations:

1. 

DNA base substitution, insertion, and deletion

2.

unequal crossing-over and related structural modifications of chromosomes

3.

partial or complete gene inversion and duplication

4.

irregular numbers of chromosomes

Substitutions, insertions, and deletions of single bases are common.  For example, an adenine can be accidentally substituted for a guanine in a sequence of bases.  Such small errors in copying DNA are referred to as point mutations.  There is a self-correcting mechanism in DNA replication that repairs these small errors, but it does not always find every one of them.

What Causes Mutations to Occur?

Structural modifications of chromosomes generally occur as a consequence of the crossing-over process during cell division.  Normally, there is an equal exchange of end sections of homologous chromosomes.  Occasionally, there is a reunion of an end section onto a chromosome that is not homologous.  Likewise, there can be an orphaned end section that does not reattach to any chromosome. The genes on such orphans are functionally lost. 

Sometimes, extra copies of one or more genes are produced when a DNA molecule is replicated.  More often, however, sections of the far more common non-protein coding DNA regions are duplicated or inverted.  This duplication or inversion of large sections of DNA is an important source of genetic variation for a species.  Spare copies of genes or inactive genes can mutate and change their function over time thereby producing a new variation that natural selection can favor or reject.  Large-scale evolutionary changes in a species line generally occur in this way.  Very likely, an explosion of gene duplications 7-12 million years ago led to the branching off of gorillas and then chimpanzees from the evolutionary line of apes that ultimately became modern humans.

Irregular numbers of chromosomes can occur as a consequence of errors in meiosis and the combining of parental chromosomes at the time of conception.  Such is the case when there are three instead of two autosomes for pair 21 (i.e., trisomy 21).  This specific error is characteristic of Down syndrome.

Types of
mutations

 

 

drawings of the types of mutations--point mutation altering a base unit in a DNA molecule, structural modification of a chromosome (loss of part of a chromatid), and irregular numbers of chromosomes (extra or missing ones)

In order for a mutation to be inherited, it must occur in the genetic material of a sex cell.  It is likely that most sex cells contain gene mutations of some sort.  It is now thought that the frequency of new mutations in humans is about 1 for every 10,000 genes per generation.  If this number is correct, every individual would be expected to have 2-3 mutations on average.  Complicating the picture is the fact that mutation rates for different genes and chromosomes apparently vary.  Mutations are common occurrences even in healthy people.  The majority of them probably do not confer a significant advantage or disadvantage because they are point mutations that occur in non-gene coding regions of DNA molecules.  They are relatively neutral in their effect.  However, some mutations are extremely serious and can result in death before birth, when an individual is still in the embryonic or early fetal stages of development.

Mutations can occur naturally as a result of occasional errors in DNA replication.  They also can be caused by exposure to radiation, alcohol, lead, lithium, organic mercury, and some other chemicals.  Viruses and other microorganisms may also be responsible for them.  Even some commonly prescribed drugs are thought to be potential mutagens .  In this group are

1. 

androgens (steroid hormones that control the development and maintenance of masculine characteristics)

2.

ACE inhibitors (a class of blood pressure medication)

3.

streptomycin and tetracycline (two classes of antibiotics)

4.

vitamin A

Mutations appear to be spontaneous in most instances.  That does not mean that they occur without cause but, rather, that the specific cause is almost always unknown.  Subsequently, it is usually very difficult for lawyers to prove in a court of law that a particular mutagen is responsible for causing a specific mutation in people.  With the aid of expert scientific testimony, they can often demonstrate that the mutagen can cause a particular kind of mutation.  However, that is not the same thing as proving that a plaintiff's mutation was caused by that mutagen instead of some others.

In order for a mutation to be subject to natural selection, it must be expressed in the phenotypes of individuals.  Selection favors mutations that result in adaptive phenotypes and eliminates nonadaptive ones.  Even when mutations produce recessive alleles that are seldom expressed in phenotypes, they become part of a vast reservoir of hidden variability that can show up in future generations.  Such potentially harmful recessive alleles add to the genetic load of a population.  Even mutations that have a neutral effect can become advantageous or harmful if the environment changes to select for or against them.

The great diversity of life forms that have been identified in the fossil record is evidence that there has been an accumulation of mutations producing a more or less constant supply of both small and large variations upon which natural selection has operated for billions of years.  Mutation has been the essential prerequisite for the evolution of life.