Genetic variation

The pop music take on mutation

Genetic analysis requires variants. Genetic variants arise through mutation.

A gene mutation is a situation where a new allele arises through a change in the DNA code.

A chromosome mutation is a situation where a segment of chromosome, a whole chromosome, or a set of chromosomes changes. Changes in sets of chromosomes will be discussed in the section on Polyploidy.

Gene mutations

Genes and alleles: _____________________________

• Sudden, random heritable change in the genetic material

• Without mutation all genes would exist in only one form (monomorphism)

• Mutation is the source of all genetic variation and therefore the basis of evolutionary change

What about recombination?

A digression on mutation, genetic polymorphisms, and molecular markers.

Mutations are changes in the genetic material. Not all genetic material (DNA) is coding. Therefore, mutations can cause changes in sequence that are not in coding regions.

II. Mechanisms of mutation

Mutations can be induced or spontaneous ( Details on mechanisms of spontaneous and induced mutations)

• Common agents of induced mutation are radiation and chemicals

  The mutation rate and type of mutation may vary with the induction agent

• Naturally occurring mutations are spontaneous 

  Spontaneous mutations are usually quite rare: average mutation rates are 10^-5 – 10^-8 events per locus per generation (in prokaryotes) and similar rates are assumed to be operating in eukaryotes. 

  Rarity is due to both infrequent occurrence and the efficacy of biological repair (Details on biological repair).

III. Where mutations occur is important

• In order to be inherited - transmitted via sexual reproduction - both induced and spontaneous mutations must occur in the germ line

• Somatic mutations can be propagated asexually, and some are of great horticultural value

IV.  The molecular basis of mutation

The most common type of mutation is a “loss of function”.   

A complete summary of gene mutations at the molecular level. Some key types of mutations are:

A. Base substitutions, which are of two types:

• transition: purine® purine (e.g. A®G); pyrimidine® pyrimidine (e.g.C®T)
• transversion: purine® pyrimidine (A®T) or pyrimidine® purine (C®G)

Transitions are more common than transversions, but they are usually edited (see details on biological repair)

Three consequences of base substitutions are:

• Silent mutations: Different triplet, but same amino acid: AGG ®CGG (triplet still codes for Arg)
• missense mutations: Different triplet, different amino acid: GAA®GUA (Glu®Val).  If the change is to a chemically similar amino acid, the missense mutation is synonymous; if to a dissimilar amino acid, it is non-synonymous). 
• nonsense mutation: From amino acid-coding triplet to stop codon: CAG®UAG

B. Frameshift mutations occur when there are base pair additions and deletions, which are not in multiple of three, which lead to a change in reading frame. This can lead to chain termination, and thus can have a major effect on phenotype.

C. Consider the effects of the different types of mutations in different regions of the genome

• Intergenic regions

 

• Genes
  • promoter
    
  • intron
  • exon
  • UTRs

     

 

V.  Using mutants for genetic analysis:  In prokaryotic and eukaryotic model systems, mutagenesis is an invaluable tool for dissecting the genetic basis of phenotypes.  The genome size and relatively slow generation time of many higher plants (including most economically important ones) has, to some extent, limited the use and application of mutagenesis.  However, the genetic analysis of “naturally occurring” genetic variation is still rooted in mutation, since mutation is the source of allelic variation.     

A. Steps in genetic analysis:  Griffiths et al. (1999) defined steps in genetic dissection of a phenotype. In many higher plant genetic analyses, and particularly those with an applied focus, Step 2 may be replaced by a search for naturally occurring variants. However, the remaining steps are valid for any organism. A few additional minor revisions to the list, as appropriate for higher plant and applied genetics, are shown in italics.

1.  “Design an effective mutation-detection system.

2.  Use a mutagen to induce a large collection of mutants that show variations in wild-type processes. Alternatively, assemble a large collection of accessions showing the desired phenotype (stripe rust resistant germplasm example). 

3. Group the mutations into genes by using complementation (or allelism) tests.

4. Map the genes to their chromosomal loci.

5. Isolate the genes by using DNA technology.

6. Characterize the structure and function of the genes.

7. From the analysis of gene and protein (and environment) interaction, piece together an integrated picture of how the biological process under study works.”

B. Mutational analysis vocabulary:

• A germline mutation arises in the germ line, the specialized tissue(s) that will eventually give rise to gametes.  Germline mutations, accordingly, have the potential to be transmitted via the processes of sexual reproduction.  Somatic mutations, however, can only be propagated asexually and many somatic mutations are of great value in horticulture and agriculture.
• Forward and reverse mutations refer to mutation away from, and back to, the wild type.
• Loss of function refers to a loss of capacity to produce the phenotype whereas gain of function is the reverse.
• Morphological mutations have visible effects on the organism’s morphology.
• Lethal mutations are deadly.
• Biochemical mutations may not be visible to the eye, but they can have dramatic effects, e.g. an auxotroph requires an exogenous source of a nutritional compound or it will die.  

FYI: Perspectives on tilling and eco-tilling

Chromosome mutation

I. Overview:

Much as mutants are the basis for genetic analysis, chromosome aberrations are the basis of cytogenetic analysis.

Chromosome rearrangements are a gross form of mutation. If critical genetic information is lost, the aberration won't survive.

Certain genome architectures, such as polyploidy, allow for the maintenance of chromosome aberrations that would otherwise be lethal in a diploid.

For rearrangements that are not lethal, chromosome breakage and rearrangement can lead to new linkage relationships.

II. Types of chromosome aberrations:

The principal classes of chromosome rearrangements are duplications/deficiencies, inversions,  and translocations.

A. Duplications/Deficiencies:

In plants, deficiencies usually abort while duplications will not. Deficiency heterozygotes are usually semi-sterile.

B. Inversions: The event; meiosis

Inversions occur when there are two breaks in the chromosome, followed by reverse insertion. If there is no crossing over within the loop of an inversion heterozygote, gametes will be viable. If there is crossing over within the loop, sterility may result due to chromosomal aberrations produced as a result of the crossover. Different types of crossovers will create different aberrant chromosomes.

C. Translocations:The event; meiosis

Translocations occur when there are breaks in non-homologous chromosomes followed by translocation of the non-homologous fragments

 

 

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Role of mutations in agriculture

Alleles that are unfavorable in natural ecosystems may be favorable for agriculture

I. Shattering resistance in cereals

Not yet cloned, but mapped in many species

Evidence for "domestication" blocks of genes - e.g. shattering resistance linked with non-dormancy in rice

 

II. Semi-dwarf ("Green Revolution") genes in wheat - See Peng et al.(1999)

These are gibberillin-insensitvity genes

 

• They are probably transcription factors
• They function in transgenic rice
• They show partial dominance
• There are multiple alleles per locus
• Orthologs identified in Anadiplosis and maize

Figure 1 shows

• Phenotypes
• Southern blotting to detect dwarfing genes
• Synteny in linkage maps
  

 

Text readings:

• Chapters 15 and 16