Genotype Variation, Mutations and Recombination

From WikiLectures


Genetic Variability

Genetic variability is a measure of the tendency of individual genotypes in a population to vary from one another. The variability of a trait describes how much that trait tends to vary in response to environmental and genetic influences. It is important to note that the sequence of nuclear DNA between any two humans is nearly 99.9% identical, and yet it is that 0.01% of DNA sequence differences that cause genetically determined variability among humans. On the other hand some DNA sequence differences have little or no effect on phenotype whereas others are directly responsible for causing disease. Between these two extremes the difference in DNA sequence is responsible for variation in phenotype, character, talents, susceptibility to specific diseases etc.

Basic forms of variation

  1. Continuous variation: This is the case where the individuals in a population show a graduation from one extreme to another. For example, height of individuals in the human population follows a normal distribution curve (bell-shaped curve). Characteristics which show continuous variation are controlled not by one but by the combined effect of a number of genes and is called a polygene. Thus any characteristic which results from the interaction of many genes is called polygenic inheritance. The variable assortment of the genes during prophase 1 of meiosis ensures that individuals posses a range of genes from any polygenic complex.
  2. Discontinuous variation: This is the case where there is a limited number of distinct forms within the population in other words there are no intermediate phenotypes. For example humans may be separated into groups according to their blood type i.e. 4 groups.


Genetic recombination is the process by which the combinations of alleles observed at different loci in two parental individuals become shuffled in offspring individuals. Such shuffling can be the result of recombination via intra-chromosomal recombination (crossing over) and via inter-chromosomal recombination (also called independent assortment). In other words, it is a process by which a breaking of a strand occurs and then rejoined to a different DNA molecule therefore the offspring now having a different combination of alleles from their parents.

The crucial events of meiosis are those which are responsible for recombination, which means that the combinations of alleles passed by individuals to their offspring differ from those that were passed to the individuals by their parents. This helps to a level of genetic variation.

Independent assortment

Each pair of homologous chromosomes consists of one chromosome inherited from the father and one inherited from the mother. When a pair of homologous chromosomes separate/segregate at anaphase I, one member of each pair moves to opposite poles of the cell. It is important to note that the process is not selective to which chromosome of the homologous pair, paternal or maternal, is going to move to a specific pole of the cell. Therefore the two daughter cells contain new combinations of maternally and paternally inherited chromosomes. Hence we say that we have recombination due to independent assortment (on the equatorial plate) in metaphase I

Recombination due to crossing over at chiasmata

This only affects recombination in genes located on the same chromosome. It occurs in Prophase I when homologous chromosomes pair up (one paternal and one maternal) a process called “synapsis”. The paternal and maternal chromosomes cross over forming chiasmata and exchange genetic information. Thus the recombinant sister cromatid formed contains genetic information from both father and mother.

Other mechanisms

  1. Conservative site specific recombination: This occurs when a mobile element of DNA is inserted into another strand of DNA. This is possible when the mobile element posses a segment of DNA that matches exactly the other strand, therefore allowing enzymes called integrases to insert the rest of the mobile element into the target strand. Site specific recombination systems are employed in many cellular processes, including bacterial genome replication, pathogenesis and differentiation. These systems present a potential basis for the development of genetic engineering tools.
  2. Transpositional recombination: Does not require an identical strand of DNA in the mobile element to match with the target DNA. The integrases that are involved, introduce nicks in both the mobile element and the target DNA, allowing the mobile DNA to enter the sequence. The nicks are then removed by ligases.


It is defined as a change in the DNA sequence of a cell's genome. Mutations can be divided into 3 classes or categories:

  • Genome mutations: Mutations that affect the number of chromosomes.
  • Chromosome mutations: Mutations that alter the structure of individual chromosomes. Also known as Gross mutations.
  • Gene mutations: Mutations that alter individual genes.

All 3 types of mutations occur quite often in many different cells. However, if a mutation occurs in a germline cell, it may be passed on to future generations. On the other hand somatic mutations occur by chance in a subset of cells in certain tissues and result in somatic mosaicism that cannot be transmitted.

It is important to note the fact that many types of mutations are represented among the millions of DNA variants found throughout the genome in the normal population as well as among the vast numbers of alleles at individual loci in thousands of genetic disorders. Also another important pointer is that, mutations are the drive force of evolution but they can also be pathogenic.

Genome mutations

These are changes in the number of intact chromosomes arising from errors in chromosome segregation during meiosis or mitosis. Missegregation of a chromosome pair during meiosis can cause genome mutations responsible for conditions such as Trisomy 21 also know as Down Syndrome.

Searchtool right.svg For more information see Chromosomal Abnormalities.
Searchtool right.svg For more information see Autosomal Disorders.

Chromosomal aneuploidy is produced by these so called genome mutations and they occur at a rate of one missegregation per 25 to 50 meiotic cell divisions. However this estimate is minimal since most aneuploidy fetuses are spontaneously aborted shortly after conception, due to the fact that the developmental consequences are very severe that could not sustain life and thus they go unrecognized. Genome mutations are also common in cancer cells.

Chromosome mutations

These include, partial duplications or triplications, inversions, deletions and translocations. These type of mutations can occur either spontaneously or may arise as a result of improper segregation of translocated chromosomes during meiosis. They occur at rate of one rearrangement per 1700 cell divisions. This is estimate is much less than the rate of genome mutations. As with genome mutations these types of mutations are most of the times incompatible with life. Chromosome mutations are also frequently seen in cancer cells.

Gene mutations

  • Gene mutations are changes in the DNA sequence (nuclear or mitochondrial) that may be as small as a single nucleotide to as large as involving millions of base pairs.
  • These include, base pair substitutions, insertions and deletions. They can occur by either of the following two mechanisms: erros the occur during normal replication, or mutations that arise because of a fault in the reparation mechanism, i.e. failure to repair DNA after damage and to reconstruct the original DNA sequence.
  • Some mutations are induced by mutagens (these include chemical and physical agents, as well as biological i.e. viruses) , whereas others occur spontaneously.
  • DNA replication errors: Most of the errors are removed and subsequently corrected by DNA repair enzymes by first recognizing the faulty strand in the newly synthesized double helix and then replacing it with the correct complementary base. This process is called proof reading. DNA polymerase is an enzyme that duplicates the double helix through a combination of base pairing and molecular proof reading.
  • Repair of DNA damage: Many nucleotides are damaged everyday by spontaneous chemical processes like, demethylation, depurination or deamination due to chemical mutagens., that may be natural or otherwise, and by exposure to ionizing radiation or ultraviolet light. Some, but not all of these damages are repaired. Even if the damage is recognized and excised the repair machinery might misread the complementary strand and introduce mutations, by introducing incorrect bases.
  1. Nucleotide substitutions (point mutations)

Remember, substitution for one purine for the other or one pyrimidine for the other are called transitions. However, replacement of a purine for a pyrimidine and vice versa is called transversion.

  • Missense mutations: When a single nucleotide is substituted in a DNA sequence it can result in a triplet of bases the code for a different amino acid than what was originally intended. Such mutations alter the "sense" of the coding strand and hence the name given, "missense". Base substitutions outside the coding sequence can also have devastating effects on the gene product.
  • Nonsense mutations: Substitution that result in the formation of one of the three termination codons where it used to be a codon coding for an amino acid is called a "nonsense mutation". The translation of the mRNA ultimately stops at the new termination codon with one of two possible consequences. Either the partial mRNA formed is unstable and no translation is possible (nonsense mediated mRNA decay) or, even if the mRNA formed is stable enough to be translated, the truncated protein is usually so unstable that is quickly degraded. A point mutation can also destroy a termination codon and allow translation to continue to the next termination codon.
  • Silent mutations: These include substitutions of a base that results in coding for the same amino acid, therefore, no harm done.
  • RNA processing mutations: A series of modifications are needed to produce a mature mRNA from an immature initial RNA transcript. These include, 5' capping, polyadenylation, and splicing. These steps in modifiaction are dependent on specific sequences among the mRNA.

In the case of splicing introns have to be excised from the unprocessed mRNA and exons have to be spliced together to form a mature mRNA. For this to happen, particular nucleotide sequences located at or near the intron-exon (3' acceptor site) or the exon-intron (5' donor site) junctions are required. Thus, mutations that affect these sites interfere with normal RNA splicing.

  1. Insertions and deletions (indels)
  • Small deletions and insertions: Some indels affect only a small number of base pairs. When the number of bases involved is not a multiple of three (one triplet of bases makes a codon coding for one amino acid), the reading frame is altered, or better, shifted. Such mutations are called frameshift mutations. If the number of bases is a mutliple of three then no frameshift occurs and there will be an insertion or deletion of corresponding amino acids in the translated gene product.
  • Large deletions and insertions: Alterations of gene structure that are large enough to be detected by Souther blotting are relatively uncommon but have been described by many inherited disorders. For example, deletions within the large dystrophin gene on the X chromosome in Duchene muscular dystrophy or the large neurofibromin gene in neurofibromatosis type 1.


Related articles

External links




  • NUSSBAUM, Robert L – MCINNES, Roderick R – WILLARD, Huntington F. Genetics in Medicine. 7th edition. Philadelphia : Saunders Elsevier, 2007. 585 pp. ISBN 9781416030805.
  • CHAMPE, Pamela C – HARVEY, Richard A – FERRIER, Dennis R. Lippincott's Illustrated Reviews : Biochemistry. 4th edition. Philadelphia : Lippincott Williams & Wilkins, 2008. 520 pp. ISBN 978-1-6083-1521-5.

Further reading