Mendel, Chromosomes, and Gene Linkage

Mendel and Chromosomes

• Genes reside on chromosomes
• Chromosomes are a linear arrangement of genes
• The number of genes exceeds the number of chromosomes, resulting in linkage

No Linkage Between Two Genes

• AaBb x aabb cross produces offspring in a 1:1:1:1 ratio
• Meiosis results in a 1:1:1:1 gamete ratio when no linkage exists between two genes

Complete Linkage Between Two Genes

• AaBb x aabb cross produces offspring in a 1:1 ratio
• Meiosis results in a 1:1 gamete ratio, with no recombination between genes that are completely linked

Two Genes With Recombination

• AaBb x aabb cross produces four different gametes
• Meiosis yields 4 gametes: 2 parental, 2 recombinant
• Recombinant gametes result from a single crossover event
• The gamete ratio varies due to recombination

Interlocus Distance

• The probability of crossing over is proportional to the distance between two loci on a single chromosome, known as the interlocus distance
• There is a higher probability of a crossover event with increased distance between loci
• Shorter distances correlate to low likelihood of crossovers and a low percentage of recombinant offspring
• Longer distances correlate to a high likelihood of crossovers and a high percentage of recombinant offspring

Thomas Morgan's Contribution

• Drosophila (fruit flies) were used in genetic experiments
• Studied X-linked genes
• Examined two genes at a time

Morgan's Observations

• F2 generation predominantly has original phenotypes (A_B_ & aabb)
• Some F2 offspring showed a mix of wild-type and mutant traits (A_bb & aaB_)
• Different genes yield similar results
• Different genes yield different numbers of "recombinants"

Morgan's Interpretations

• A connection exists between recombinant phenotypes and chiasma observed in meiosis
• Recombination amount related to the distance between genes

Alfred Sturtevant and Chromosome Mapping

• Recombination frequency is approximately additive
• Predicted gene order (closer equates to lower recombination frequency)
• Example: y-w = 0.5%, y-m = 35.4%, w-m = 34.5%
• Map distances are measured in centiMorgans (cM)
• 1 map unit (mu) equals 1% recombination, equivalent to 1 cM

Key Points About Single Crossovers (SCOs)

• Not all SCOs are detectable
• SCOs lead to the exchange of segments between two non-sister chromatids
• Allele linkage between A and B and between a and b remains unchanged

Significance of Single Crossovers, Recombination Frequency, and Gene Distance

• Map distance is proportional to % Crossover and the % Noncrossover

Determination of Expected Phenotypes for Genes 60 Map Units Apart

• Two genes that are 60 map units apart are expected to show independent assortment

Mapping Gene Order

• Single crossovers enable the inference of distances between genes
• Gene order is more difficult to determine
• Multiple crossover events, examined in three or more genes, allow the inference of gene order

Double Exchanges

• These are rare events involving two independent crossovers
• Frequency is calculated as P(1st crossover) x P(2nd crossover)

Three-Point Mapping Conditions

• One parent is heterozygous at all three loci
• The other parent is homozygous recessive at all three loci
• Able to determine the genotype based on the phenotype
• A large number of progeny are needed

Three-Point Mapping

• Involves tracking three linked genes simultaneously to determine their order and map distances
• Double crossovers are rare events and can help determine gene order

Inferring Gene Order

• Compare parental and double crossover (DCO) genotypes
• The middle gene is the one that swaps places in the DCO gametes

Determining SCO Events

• Compare parental and single crossover (SCO) genotypes to infer which genes are involved in each event

Calculating Recombination Frequencies

• For each gene pair, calculate recombination frequency: (number of SCOs + number of DCOs) / total offspring
• Frequency of recombination between two genes can be determined by tallying a number of offspring with the recombinant phenotype

Accuracy of Mapping Genes

• Accuracy decreases as the physical distance increases
• Likely due to undetected double recombination events

Interference

• A measure of the degree to which one crossover event influences the occurrence of another in the same region of a chromosome
• The expected frequency of DCO equals prob(SCO1) x prob(SCO2)
• Coefficient of coincidence (C) = observed DCO / expected DCO
• Interference (I) = 1 - C
• I ranges from negative to 0 to 1 (positive) where 0 = none, 1 = complete
• Positive interference = less DCO than expected
• Negative interference = more DCO than expected

Example Calculation of Interference

• Example:
• y-w = 1.56%
• w-ec = 4.06%
• DCO = 6/10000
• Expected DCO = (0.0156) * (0.0406) = 0.00063
• C = 0.0006 / 0.00063 = 0.952
• I = 1 − C = 1 - 0.952 = 0.048, a positive interference

Phenotypic Classes

• Phenotypic classes of offspring representing double crossovers occur less frequently than single crossover classes

Example #2 - Three Linked Genes in Pigs

• Eye color, skin color, and tail shape are each controlled by a single gene
• Cross triple heterozygous males with triple homozygous recessive females and record the phenotypes of the offspring (100 total)

Gene Map

• W 12cM S 31cM P
• Calculate I for the example.
• w-s = 12% and s-p = 31% with DCO = 3/100 = 0.03
• Expected DCO = (0.12) * (0.31) = 0.0372
• C = 0.03 / 0.0372 = 0.806
• I = 1 - C = 1 - 0.806 = 0.194
• A positive interference

Chromosome Structure

• Creighton and McClintock discovered physical proof that Chiasma = Recombination
• C = Colorless/Colored seeds
• Wx = Starchy/waxy carbos
• Provided proof that the chromosome was structurally different
• Proved that pieces of the chromosomes were swapped proving recombination occurs