CH 15: The Chromosomal Basis of Inheritance Mendel described, unknowingly, that inheritance has its physical basis in the behavior of chromosomes. With the help of the rediscovery of Mendel’s publications, several researchers in the early 1900’s proposed that genes are located on chromosomes. The behavior of chromosomes during meiosis was strong support for Mendel’s laws of segregation and independent assortment and was in direct conflict with the blending hypothesis. T. H. Morgan A. H. Sturtevant

Morgan’s Experimental Evidence from Fruit Flies 1910 – Discovery of the white eye mutation 1930 – Nobel Prize

Correlating Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair Morgan mated his single white-eyed male fly (mutant) with red-eyed female flies (wild type): The F1 generation all had red eyes except for 3!. The F2 generation showed the 3:1 red:white eye ratio, but only males had white eyes.

P Cross: Xw Y Xw+ Xw+ Xw Xw+ Y Xw Y x Xw+ Xw+ Correlating Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair Morgan determined that the white-eye mutant allele must be located on the X chromosome: wild type = Xw+; mutant = Xw. Task: Sketch two Punnett Squares that model this X-chromosome hypothesis. Xw Y Xw+ Xw+ Xw Xw+ Y P Cross: Xw Y x Xw+ Xw+

F1 Cross: Xw+ Y Xw+ Xw+ Xw+ Y Xw Xw+ Xw Xw Y Xw+ Y x Xw+ Xw Correlating Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair Morgan determined that the white-eye mutant allele must be located on the X chromosome: wild type = Xw+; mutant = Xw. Task: Sketch two Punnett Squares that model this X-chromosome hypothesis. Xw+ Y Xw+ Xw+ Xw+ Y Xw Xw+ Xw Xw Y F1 Cross: Xw+ Y x Xw+ Xw

Correlating Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair Morgan’s discovery that transmission of the X chromosome in fruit flies correlates with inheritance of the eye-color trait was the first solid evidence indicating that a specific gene is associated with a specific chromosome. Yet, we now know that each chromosome has hundreds or thousands of genes, and these genes are therefore linked. Linked genes tend to be inherited together because they are located near each other on the same chromosome.

How Linkage Affects Inheritance Morgan first mated true-breeding wild-type flies with black, vestigial-winged flies to produce heterozygous F1 dihybrids, all of which are wild-type in appearance: P b+ b+ vg+ vg+ X b b vg vg F1 ALL b+ b vg+ vg F1 Test Cross b+ b vg+ vg X b b vg vg F2 Punnett Square Prediction?

How Linkage Affects Inheritance P b+ b+ vg+ vg+ X b b vg vg F1 b+ b vg+ vg F1 Cross b+ b vg+ vg X b b vg vg F2 Punnett Square Prediction for 2,300 F2 offspring assuming unlinked genes and independent assortment?

How Linkage Affects Inheritance P b+ b+ vg+ vg+ X b b vg vg F1 b+ b vg+ vg F1 Cross b+ b vg+ vg X b b vg vg F2 Punnett Square Prediction for 2,300 F2 offspring assuming unlinked genes and independent assortment? b+ vg+ b+ vg b vg+ b vg b+ b vg+ vg 575 b+ b vg vg b b vg+ vg b b vg vg If genes are unlinked and on different chromosomes, 50% should be Recombinants (new combinations, not like either parent)

How Linkage Affects Inheritance P b+ b+ vg+ vg+ X b b vg vg F1 b+ b vg+ vg F1 Cross b+ b vg+ vg X b b vg vg F2 Punnett Square Prediction for 2,300 F2 offspring assuming unlinked genes and independent assortment? b+ vg+ b+ vg b vg+ b vg b+ b vg+ vg 965 b+ b vg vg 206 b b vg+ vg 185 b b vg vg 944 But < 50% were Recombinants

How Linkage Affects Inheritance P b+ b+ vg+ vg+ X b b vg vg F1 b+ b vg+ vg F1 Cross b+ b vg+ vg X b b vg vg F2 Punnett Square Prediction for 2,300 F2 offspring assuming unlinked genes and independent assortment? b+ vg+ b+ vg b vg+ b vg b+ b vg+ vg 965 b+ b vg vg 206 b b vg+ vg 185 b b vg vg 944 Parental type offspring

How Linkage Affects Inheritance P b+ b+ vg+ vg+ X b b vg vg F1 b+ b vg+ vg F1 Cross b+ b vg+ vg X b b vg vg F2 Punnett Square Prediction for 2,300 F2 offspring assuming unlinked genes and independent assortment? b+ vg+ b+ vg b vg+ b vg b+ b vg+ vg 965 b+ b vg vg 206 b b vg+ vg 185 b b vg vg 944 Nonparental type offspring

How Linkage Affects Inheritance P b+ b+ vg+ vg+ X b b vg vg F1 b+ b vg+ vg F1 Cross b+ b vg+ vg X b b vg vg F2 Punnett Square Prediction for 2,300 F2 offspring assuming unlinked genes and independent assortment? b+ vg+ b+ vg b vg+ b vg b+ b vg+ vg 965 b+ b vg vg 206 b b vg+ vg 185 b b vg vg 944 Nonparental type offspring that compose less than 50% of the total: evidence of linked genes and crossing over during Meiosis. Statistical Support?

Morgan’s Test Cross

How Linkage Affects Inheritance Morgan determined that: Genes that are close together on the same chromosome are linked and do not assort independently. Recombination occurs < 50% of the time Unlinked genes are either on separate chromosomes or are far apart on the same chromosome and assort independently (e.g. A and E). Recombination (production of offspring phenotypes different from the parents) occurs ~50% of the time.

Linkage Mapping: Using Recombination Data Alfred Sturtevant (one of Morgan’s students) proposed a hypothesis: recombination frequencies depend on the distances between genes on a chromosome. Sturtevant’s prediction: the farther apart two genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency. Sturtevant first built a linkage map for the genes that, when mutated, produce the black, cinnabar, and vestigial phenotypes. Linkage maps show order, but not actual location (cytogenic maps). Why 17%, and not 9% + 9.5% = 18.5%?

Inheritance of Sex-Linked Genes The sex chromosomes have genes for many characters unrelated to sex. A gene located on either sex chromosome is called a sex-linked gene. Sex-linked genes follow specific patterns of inheritance.

Inheritance of Sex-Linked Genes Some recessive alleles found on the X chromosome in humans cause certain types of disorders: Color blindness (cone defect or absence) Duchenne muscular dystrophy (rapidly worsening muscle weakness) Hemophilia (absence of one or more of the proteins required for blood clotting)

Abnormal Chromosome Number Large-scale chromosomal alterations often lead to spontaneous abortions or cause a variety of developmental disorders. When nondisjunction occurs, pairs of homologous chromosomes do not separate normally during meiosis. Gametes then contain two copies (n + 1) or no copies (n - 1) of a particular chromosome.

Abnormal Chromosome Number Aneuploidy results from the fertilization of gametes in which nondisjunction occurred, and is a condition in which offspring have an abnormal number of a particular chromosome. If a zygote is trisomic, it has three copies of a particular chromosome. If a zygote is monosomic, it has only one copy of a particular chromosome.

Abnormal Chromosome Number Polyploidy is a condition in which there are more than two complete sets of chromosomes in an organism. Polyploidy can occur in every cell of an organism, or in specific tissues: seed endosperm, Drosophila salivary glands, human liver cells. The Plains Viscacha Rat (Tympanoctomys barrerae) of Argentina is tetraploid and isolated mechanically (prezygotic) from other species because of both tetraploidy and sperm morphology.

Alterations of Chromosome Structure Breakage of a chromosome can lead to four types of changes in chromosome structure:

Inheritance of Organelle Genes Extranuclear genes are genes found in organelles in the cytoplasm. The inheritance of traits controlled by genes present in the chloroplasts or mitochondria depends solely on the maternal parent because the zygote’s cytoplasm is maternally inherited. United Mitochondrial Disease Foundation