Chromosomal Theory of Inheritance

• Chromosomes weren't observed until the late 1800s with better microscopes and techniques.
• Scientists then connected Mendel's laws, meiosis, and chromosomes.
• Walter Sutton and Theodor Boveri independently discovered that genes reside within chromosomes.
• Sutton studied grasshoppers, while Boveri studied sea urchins.
• In 1902-1903, Sutton and Boveri independently published papers proposing genes are at specific locations on chromosomes, and behavior during meiosis explains Mendel's Law.
• This is known as the chromosomal theory of inheritance.
• Observations supporting the theory include how chromosomes come in homologous pairs, one from each parent.
• Homologous pairs separate during meiosis, reflecting Mendel's law of segregation.
• Different chromosome pairs sort into gametes independently.
• The chromosome theory was initially controversial due to a lack of direct evidence.
• Thomas Hunt Morgan and his student studied fruit fly genetics.
• Fruit flies (Drosophila melanogaster) were chosen for their practicality: cheap, easy, and fast to grow.
• Morgan confirmed the chromosomal theory by finding a mutation in fruit flies affecting eye color, producing white eyes instead of red.
• The eye color gene was inherited differently by male (XY) and female (XX) flies, leading Morgan to realize that the gene was on the X chromosome.
• The first white-eyed mutant was male; when crossed with a red-eyed female, F1 offspring were all red-eyed, showing white is recessive.
• When the F1 generation was crossed, all female F2 were red-eyed, and half the male F2 were white-eyed.
• This confirmed the X chromosome inheritance pattern.

Genetic Linkage

• Genes close together on a chromosome tend to "stick together" and are inherited as a pair.
• This phenomenon is called genetic linkage.
• Linked genes produce offspring ratios inconsistent with Mendel's law of independent assortment.
• Genes on separate chromosomes, or very far apart on the same chromosome, assort independently.
• Genes on the same chromosome that are very far apart assort independently due to crossing over.
• Crossing over puts new alleles together, often occurring equally.
• When genes are very close together on the same chromosome, crossing over still can occur, however, the outcome is significantly different.
• Instead of assorting independently, close genes tend to "stick together."
• When genes do this, they are said to be linked.
• Gametes from linked genes appear in unequal proportions.
• Parental genes have the same allelic configuration as the parents.
• Recombinant genes contain allelic configurations formed only by crossing over between close genes.
• Crossing over between very close genes rarely occurs, leading to low recombinant frequencies.
• Crossovers during meiosis occur randomly along the chromosome, so crossover frequency depends on gene distance.
• Shorter distances between genes mean less likely crossing over will occur.
• Likewise, the longer the distance between genes, the greater chance crossing over can occur.
• Recombination event frequency estimates the relative distance between genes.
• Very close genes have few recombination events (tightly linked), while slightly further apart genes have more (less tightly linked).

Recombination frequency

• In fruit flies, purple (pr) genes have two forms: Dominant red eyes (pr+) and recessive purple eyes (pr).
• Vestigial (vg) genes have two forms: Dominant long wings (vg+) and recessive short wings (vg).
• Applying testcross to a double heterozygous female fly can read genotype of each gamete based from the physical appearance of the offspring.
• Parental genes are more numerous.
• To quantitatively measure linkage, calculate the recombination frequency (RF) between the two genes.
• RF% = (Recombinants / Total Offspring) x 100
• Recombinants come from crossing over and are under-represented (low count).

Linkage Maps

• Recombination frequency has been historically used to build linkage maps.
• These are chromosomal maps based on recombination frequencies.
• RF is not a direct measure of physical distance, but an approximation.
• A larger RF suggests genes are likely further apart, while a smaller RF suggests genes are likely closer together.
• RF maxes out at 50%.
• 50% is the largest RF that can directly measure between genes.
• Higher percentages suggest being unlinked.
• Comparing recombination frequencies can determine gene order on a chromosome is possible.
• Recombination frequencies among all three possible pairs of genes(AC, AB, BC), figures out which genes lie furthest apart, and other gene lies in the middle.
• Distances in linkage maps may be expressed as centimorgans (cM) or map units (mu).