Lecture#10 Alleles, Dominance, and Morphs

4/7/18 BIOLOGY 207 - Dr. Locke Lecture#10 – Alleles, Dominance, and Morphs Required readings and problems: Reading: Open Genetics, Chapter 3, 4 Problems: Chapter 3, 4

Optional Griffiths (2008) 9th Ed. Readings: pp 31-42, 223-230, 54-55 Problems: 9th Ed. Ch. 6: 1-7,10,12,13,16,18,21,22,25,28 Campbell (2008) 8th Ed. Readings: Concept 14.4 See: Supplement on "Muller's Morphs. See web site.

Concepts: How do mutant alleles interact at a single locus? 1. Multi-cellular organism can have somatic and germline mutations. 2. DNA sequence can be altered and a mutant or variant can result. 3. The functional allele is usually dominant to the non-functional allele in individuals with both alleles (called a heterozygote). 4. Dominance/recessiveness is not always complete. 5. Genetic tests can identify mutations that have elevated, reduced, eliminated, or changed functions (Muller's Morphs

Biol207 Dr. Locke section Lecture#10 Fall'11 page 1 4/7/18 Multi-cellular organisms (animals) A mutation, occurs in the DNA of a single cell. - will be passed it on to the cell's descendants directly. Multi-cellular organism: will pass on to the cell's descendants and MAY be passed on to the organism's progeny.

Somatic vs Germline Cells in multi-cellular organisms

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 (eggs or sperm)  - are passed on to the next generation

Biol207 Dr. Locke section Lecture#10 Fall'11 page 2 4/7/18 Somatic vs Germline Mutations

Somatic Mutations – Occur in somatic cells (example: Fox) - mutant cells 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 affect (phenotype) in the individual in which they occur - will NOT be passed on to the next generation (progeny)

Mosaic - an individual composed of two (or more) types (lines) of cells that differ in their genetic composition

Germline (germinal) Mutations – Occur in germline cells - can be passed on to the next generation of organisms - don’t affect the individual in which they occur

Animals -> segregate these cells from somatic cells Plants -> somatic cells become germ cells; therefore somatic mutations can become germline mutations

Biol207 Dr. Locke section Lecture#10 Fall'11 page 3 4/7/18 Genotype and Phenotype ( P = G + E + I ) 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 (plus an interaction between the two) Mutations in haploid and diploid organisms Geneticists use the phenotype to infer genotype or possible genotypes for an individual. Haploids - e.g. bacteria, haploid yeast - usually one copy per gene - single cells - expression of gene affects the cell's phenotype directly

Biol207 Dr. Locke section Lecture#10 Fall'11 page 4 4/7/18 Diploids e.g. diploid yeast, Drosophila and other animals and plants - two copies of each gene - interactions of alleles - often multicellular - different tissues - expression is NOT direct

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 Dominant and Recessive 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.

Biol207 Dr. Locke section Lecture#10 Fall'11 page 5 4/7/18 Heterozygotes vs homozygotes Diploid individuals have 3 possible combinations of two alleles: RR ---> homozygote - both alleles are R rr ---> homozygote - both alleles are r Rr ---> heterozygote - one of each allele True-breeding strains - a population of individuals that shows no variation for a particular character. Example: Mendel's Round or wrinkled character of the pea

Parents:

Gametes:

Heterozygote Progeny:

Phenotype:

Dominant vs recessive  Heterozygote ---> phenotype is key to determining dominance/recessiveness

Biol207 Dr. Locke section Lecture#10 Fall'11 page 6 4/7/18 The most common circumstance: Rr has a normal (wild type) phenotype, - the single normally functioning allele, R, provides sufficient function to produce a normal phenotype.

Example: gene encodes an enzyme

Note 1: 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 2: The terms dominant and recessive are always used in relation to another alleles - in a diploid individual Dominance and recessive are not an innate property of an allele but a relative one. Note 3: Notation - Frequently capital letters are used to denote dominant alleles while the recessive alleles are given the lower case equivalent.

Biol207 Dr. Locke section Lecture#10 Fall'11 page 7 4/7/18 Incomplete dominance (semi-dominance) Alleles of genes do not always exhibit simple Dominance/Recessive relationship Sometimes there is an intermediate (or blended) phenotype in the heterozygote

Example in "Four-o'clock" plants Strains have flowers with either:  Red petals CRed / CRed - homozygotes  White petals CWhite / CWhite - homozygotes  Heterozygote CRed / CWhite = has a pink colour (intermediate between the two homozygotes)

Co-dominance In certain circumstances both alleles can be seen in the phenotype.

Example: Human Blood types HbS and HbA Fig: http://www.mun.ca/biology/scarr/Hemoglobin_Electrophoresis.html Can see both alleles and thus distinguish the homozygotes from the heterozygote.

Note: sickle-cell anemia disease is recessive phenotype of HbS/HbS individuals

Biol207 Dr. Locke section Lecture#10 Fall'11 page 8 4/7/18 Allele - a changed form of a gene; an allelic form; an allele.

Allelic forms: Wild type allele, or "normal" allele - functional - What is wild type?

Variant allele - the DNA sequence is different from wildtype - produce a product that is active and functional (yet have bp changes in the gene) - Mutant Allele (Fig vg alleles) - the DNA sequence is different from wild type; a change in gene structure -> substitution, deletion or duplication - makes the gene (Muller's morphs) 1) non-functional – null - loss of function 2) less functional - leaky 3) more functional – gain of function (same or different) 4) new function 5) dominant negative function

Allelic series – many different mutations (alleles) at the same locus

Biol207 Dr. Locke section Lecture#10 Fall'11 page 9 4/7/18 General classification of germline mutants The mutation's effect on the organism.

1) Morphological mutations - change in the form of the organism - size, shape, color, number, etc.

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: Phenotype = Genotype + Environment + Interaction - expresses mutant phenotype only under specific environmental conditions Under restrictive conditions they express the mutant phenotypic; while under permissive conditions they show a wild type phenotype - e.g.: temperature sensitive -> Siamese cat

4) Biochemical mutations - produce auxotrophic mutants from prototrophic parents - a specific type of the conditional mutation class. e.g. - your lab exercises

Biol207 Dr. Locke section Lecture#10 Fall'11 page 10 4/7/18 "Muller's morphs" classification - (1932) H.J. Muller (1946) was awarded Nobel prize for his contributions to radiation genetics. He designated five classes of mutant as "amorph, hypomorph, hypermorph, neomorph and antimorph - "morph" meaning "form" Amorph - A- absence - mutation with complete absence of wild type function - also called "null" mutation - no function - no expression of wild type gene at any level - eg. gene deleted - deletion - loss-of-function - loss of enzymatic function Hypomorph - hypo -> less than -> less than wild type level of expression of the wild type gene - same quality - range from slightly less than wild type to almost complete loss (amorph) - reduction-of-function - also referred to as "leaky" - reduced activity of enzyme

Biol207 Dr. Locke section Lecture#10 Fall'11 page 11 4/7/18 Hypermorph - hyper -> more than -> more than wild type level of gene expression - same quality more quantity - gene duplication - 2 genes -> more product- more enzyme activity - gain-of-function - more of the same Neomorph - neo -> new - mutations which create a new and different from the wild type function - gain-of-function - novel function e.g. Drosophila antennapedia, aristapedia Antimorph - anti -> against - mutant gene product results in a reduction or loss in the function and interferes with normal gene product from any wild type gene that may be present

Class demonstration. See: Supplement on "Muller's Morphs" on web site

Biol207 Dr. Locke section Lecture#10 Fall'11 page 12 4/7/18

Summary The several schemes for classifying mutations are not mutually exclusive.

They describe mutations at different levels - DNA, chemical level - e.g. frameshift, - gene product level - e.g. functional/non-functional - phenotypic level, mutant vs wild type

"Muller's Morphs" classify all types of mutations - amorph, - hypomorph, - hypermorph, - neomorph - antimorph

Allelic interactions give us:  Dominant vs. recessive  Co-dominant  Incomplete (semi-) dominant

Biol207 Dr. Locke section Lecture#10 Fall'11 page 13