Download Lecture#10 - Classification of mutations and gene function Readings

Lecture 10; 2007
Biology 207; Section B2; Good
Lecture#10 - Classification of mutations and gene function
Readings:
Griffiths et al (2000)
8th Edition: Ch. 6 pp192-199 , Ch 16 pp 535-537.
7th Edition: Ch. 15 pp 467-484
Problems:
Concepts:
How do DNA mutations affect the organism?
1. DNA sequence can be altered and a mutant or variant can result.
2. Multi-cellular organism can have somatic and germline mutations.
3. From the wide variety of mutational possibilities for most genes (alleles), we can
usually distinguish only functional and non-functional alleles.
4. The functional allele is usually dominant to the non-functional allele in individuals with
both alleles (called a heterozygote).
5. Mendel's results demonstrate the process of segregation.
Mutation - change in the DNA sequence can give rise to a phenotype if it modifies
a gene: This definition can be a bit vague, in the sense that the phenotype needs to be
defined. (eg. A mutation may affect a sequence change that can be detected as an
RFLP or single base pair change (SNP = Single Nucleotide Polymorphism), but not
affect the protein product).
Mutant - an organism bearing a mutant gene that expresses itself in the
phenotype of the organism
Genes and Alleles
Each modified form of a gene is referred to as an allelic form; an allele.
Allelic forms:
"normal" or wild type sequence or allele - functional - What is wild-type?
variant allele
- the DNA sequence is different from wild-type
- produce a product that is active and functional (yet have bp changes in the gene)
-> mutant allele
- the DNA sequence is different from wildtype - a change in base pairs leading to a
change in gene structure - substitution, deletion or duplication
- makes the gene
1) less functional
2) non-functional -> Muller's morphs
3) mis-functional
General classification of germline mutants
Text -> The mutation's effect on the organism.
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Lecture 10; 2007
Biology 207; Section B2; Good
1) Morphological mutations - change in the form of the organism
- size, shape, color, number, etc.
eg. bithorax
2) Lethal mutations - mutation that leads to or causes death of an organism
- most commonly recessive lethal
- homozygotes die - heterozygotes are viable
3) Conditional mutations - relies on the concept of:
Genotype + Environment + Interaction (of G & E) = phenotype
- organism expresses mutant phenotype only under specific environmental conditions
Under restrictive conditions they express the mutant phenotypic (e.g., high temp.),;
while under permissive conditions they show a wild type phenotype
4) Biochemical mutations
- produce auxotrophic mutants from prototrophic parents This is really a specific type of
the conditional mutation class. e.g. - your lab exercises
Different types of mutations that have been used in developing genetic maps.
1) Morphological mutations (eg. eye colour, Drosophila, kernel colour, maize)
2) Electrophoretic enzyme variants (first used in the mid-60’s to look for genetic
variation (R. Lewontin)
3) RFLP variants (Molecular markers used for the first time). Detect changes in a
restriction enzyme site.
4) Other DNA markers which can detect either Indel’s (Insertion or Deletions),
SSR’s (Simple Sequence Repeats; used in human forensics), or SNP’s.
Mutations in haploid and diploid organisms
Haploids
- usually one copy per gene
- single cells
- expression of gene affects the cell's phenotype directly
- e.g. bacteria, haploid yeast
Diploids
- two copies of each gene - interactions of alleles
- often multicellular - different tissues
- expression is NOT direct
- e.g. diploid yeast, Drosophila and other animals and plants
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Lecture 10; 2007
Biology 207; Section B2; Good
Multi-cellular organisms
Somatic vs Germline Cells
In multi-cellular organisms the cells are divided into two primary types:
Somatic cells
- form the tissues of the organism and not used in reproduction
- not passed on to the next generation
Germline cells
- form the germ cells used in reproduction
- are passed on to the next generation
Particularly important in animals less so in plants where somatic cells become germ
tissue.
The change, or mutation, occurs in the DNA of a single cell.
Somatic vs Germline Mutations
Somatic Mutations
- occur in cells that populate the body
- a mutant cell, and its descendants, will form a clone of cells
- population of mutant cells among wild type cells
- In humans -> mutation ->cell that is cancerous -> clone of cells -> cancer
- only produce an effect (phenotype) in the individual in which they occur -> mosaic
- will NOT be passed on to the next generation of organisms
Mosaic - an individual composed of two (or more) types (lines) of cells that differ in their
genetic composition
eg. Transposable elements in corn
Germline (germinal) Mutations
- occur in the sex cells or cells that lead to sex cells (eggs or sperm)
- can be passed on to the next generation of organisms
- Animals -> segregate these cells from somatic cells
- Plants -> somatic cells can become germ cells; therefore somatic mutations can
become germline mutations
Diploids have two alleles for each gene locus
In a diploid the two alleles for each gene locus sometimes makes it difficult for an
observer to ascertain the genotype directly from the phenotype
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Lecture 10; 2007
Biology 207; Section B2; Good
Geneticists use the phenotype to infer genotype or possible genotypes for an individual.
Genotype
-the genetic constitution of an organism
-in a diploid this means the two alleles
Phenotype
-the observed properties of an organism
-produced by the genotype in conjunction with the environment
How does one infer genotype from phenotype?
Haploids - direct genotype -> phenotype
Diploids - directly inferring is not always correct since there are two alleles to be
determined
Note: The concepts of alleles, dominance, recessiveness, pairs of genes, homozygotes,
heterozygotes all come to us from the work of Gregor Mendel and his peas.
Example: Gregor Mendel's peas
Gregor Mendel did his experiments in the 1860's with the pea plant (Pisum sativum)
The pea plant is useful because it can be either:
1) Self-pollinated
- pollen fertilizes the ovum in the same individual plant (flower) and one can get
gametes of both sorts (pollen and ovum) from the same genotype (individuals)
2) Cross-pollinated
-pollen fertilizes the ovum of a different individual plant and one can get gametes of
either sort (pollen and ovum) from different genotypes (different)
True-breeding strains - a population of individuals that shows no variation for a
particular character. Example: Mendel's Round and wrinkled character of the pea
Start with two different forms of a gene: two alleles
"R" (e.g. wild type) - produces a functional product
"r" (e.g. mutant) - no functional product
Parents: true breeding
Round (RR) cross (x) to wrinkled (rr) P1
Gametes: R r
Progeny: Round (Rr) F1
Heterozygotes vs homozygotes
Diploid individuals have 3 possible combinations of alleles:
RR ---> homozygote - both alleles are R
rr ---> homozygote - both alleles are r
Rr ---> heterozygote - one of each allele
Dominant vs recessive
Diploid individuals have 3 possible combinations of alleles:
RR ---> homozygote - large R phenotype
rr ---> homozygote - small r phenotype
Rr ---> heterozygote -phenotype is ????????
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Lecture 10; 2007
Biology 207; Section B2; Good
In the most common circumstance, Rr has a normal (wild type) phenotype, because the
single normally functioning allele, R, provides sufficient function to produce a normal
phenotype.
Note: Because the "R" allele determines the phenotype in the diploid heterozygote it is
considered dominant to the "r" allele.
Because the "r" allele is masked by the "R" allele, the "r" allele is considered recessive
to the "R" allele.
Note:
1). The terms dominant and recessive are always used in relation to another alleles - in
a diploid individual
2). Dominance and recessive are not an innate property of an allele but a relative one.
Notation - Frequently capital letters are used to denote dominant alleles while the
recessive alleles are given the lower case equivalent.
Mendelian Genetics
Parents: true breeding
Round (RR; P1) cross (x) to wrinkled (rr; P2)
RR
rr
R
r
Rr
genotype
RR
Rr
rr
ratio
1
2
1
phenotype
ratio
Round
3
wrinkled
gametes
F1 progeny
R
r
R
RR
Rr
r
Rr
rr
F2 progeny
1
The wrinkled character reappeared in subsequent generations.
It was only "masked" in the F1 generation (as a heterozygote), not lost.
Assigned Problems: none
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