Chapter 15: The Chromosomal Basis of Inheritance

The Chromosomal Theory of Inheritance Genes have specific loci on chromosomes and chromosomes undergo segregation and independent assortment

Chromosomal Linkage Thomas Morgan (early 20th century) Drosophilia melanogaster(fruit flies) Associated a specific gene with a specific chromosome

P1: Mated white eyed male with red eyed female Morgan’s Experiment P1: Mated white eyed male with red eyed female F1: 100% red eyed F1 generation mated F2: 3 red : 1 white However???

Morgan’s Experiment: All females were red eyes: Half the males were red The other half were white

Morgan’s Conclusion: 1. Eye color was linked to sex 2. specific genes are carried on specific chromosomes 3. genes located on sex chromosomes exhibit unique inheritance patterns

Sex-linkage: genes located on a sex chromosome Linked Genes: Sex-linkage: genes located on a sex chromosome Linked genes: genes located on the same chromosome that tend to be inherited together

Another Morgan Experiment: This time he observed body color and wing size: Wild type = gray body (b+) and normal wings (vg+) Mutant type = black body (b) and vestigial wings (vg)

First Cross: true breeding wild type wit black vestigial wings b+b+vg+vg+ X bbvgvg F1 = all wild type phenotype (b+bvg+vg)

Second Cross: female dihybrids vs true breeding reeessive males b+ bvg+vg X bbvgvg (test cross) 2300 offspring were scored

Results: -High proportion of parental phenotypes (965 wild type, 944 black vestigial) -Low proportions of non- parental phenotypes (206 gray vestigial, 185 black normal)

Conclusion: 1. Body color and wing size are usually inherited together (genes must be on the same chromosome??)

2. Body color and wing size are only partially linked: Conclusion: 2. Body color and wing size are only partially linked:

Explaining Morgan’s Results: Recombination of unlinked genes vs. linked genes: Unlinked genes = independent assortment Linked genes = crossing over

Recombination: Production of offspring with combinations of traits different from those found in either parent!

Genetic Mapping: Genetic maps are an ordered list of the genetic loci along a particular chromosome

Genetic mapping: Recombination frequencies depend on: *Distances between genes on a chromosome

Recombination frequency refers to the percentage of recombinants occurring in the offspring

*crossing over is a random event Alfred Sturtevant: *crossing over is a random event *the farther apart the genes on a chromosome, the higher the probability that crossing over will occur, so the higher the recombination frequency

Sturtevant Reasoning: The further apart two genes are, the more points between them where crossing over can occur.

*experimental crosses reveal recombination frequencies Linkage Map: Probability of crossover between two genetic loci is proportional to the distance separating the two loci. *experimental crosses reveal recombination frequencies

Example: Drosophila Body color (b) Wing size (vg) Cinnabar (cn)

Map units: Distance between genes on a chromosome 1 map unit = 1% recombination frequency Do not correspond to physical frequencies

Seed and flower color in pea plants: Genes that are very far apart on the chromosome Crossing over is almost certain.

Frequency of crossing over is not uniform over the length of the chromosome

Map units do not portray order of genes on a chromosome

Genetic recombination Crossing over Genes that DO NOT assort independently of each other Genetic maps The further apart 2 genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency Linkage maps Genetic map based on recombination frequencies

Human sex-linkage SRY gene: gene on Y chromosome that triggers the development of testes Fathers= pass X-linked alleles to all daughters only (but not to sons) Mothers= pass X-linked alleles to both sons & daughters Sex-Linked Disorders: Color-blindness; Duchenne muscular dystropy (MD); hemophilia X-inactivation: 2nd X chromosome in females condenses into a Barr body (e.g., tortoiseshell gene gene in cats)

Sex Linked Genes: Fathers= pass X-linked alleles to all daughters only (but not to sons) Mothers= pass X-linked alleles to both sons & daughters

Sex Linked Disorders: Sex-Linked Disorders: Color-blindness Duchenne muscular dystropy (MD) hemophilia

Chromosomal Errors: Nondisjunction: members of a pair of homologous chromosomes do not separate properly during meiosis I or sister chromatids fail to separate during meiosis II

Chromosomal Errors: Aneuploidy: chromosome number is abnormal Monosomy: missing chromosome Turner Symdrome -XO Trisomy : extra chromosome Down syndrome- Trisomy- 21 Kleinfelters Syndrome- XXY Polyploidy: extra sets of chromosomes

Chromosomal Errors: Alterations of chromosomal structure: Deletion: removal of a chromosomal segment Duplication: repeats a chromosomal segment Inversion: segment reversal in a chromosome Translocation: movement of a chromosomal segment to another

Point mutations: affect protein structure and function Base pair substitution: one nucleotide pair replacing another Missense vs. Nonsense mutations Missense = altered codon still codes for an amino acid – not necessarily the right one Nonsense = changes the codon to a stop codon Premature termination leading to malfunctional proteins.

Insertions and Deletions: Adding or losing a nucleotide pair Disastrous effect on the protein Causes a Frame Shift: Nucleotides down stream of the mutation will be improperly grouped into codons that will likely produce a non- functional protein

Genomic imprinting a parental effect on gene expression Identical alleles may have different effects on offspring, depending on whether they arrive in the zygote via the ovum or via the sperm. Fragile X syndrome: higher prevalence of disorder and retardation in males

Inheritance of Organelles: Some genes are considered extranuclear: That is not found in nucleus But, in organelles such as mitochondria and chloroplasts These genes do not follow mendelian inheritance patterns Randomly assorted to gametes and daughter cells

Inheritance of Organelles: Organelles are inherited maternally Sperm only contributes genetic information

Mutations: Plant variegation: due to mutations in the genes that control plant pigments Pattern of variegation is determined by the ratio of wild type allele vs. mutant type allele for pigmentation

Mitochondria DNA mutations: Heteroplasmy: when a cell contains both wild type and mutant type mtDNA. Disorders usually affect nervous and muscular systems They require the most energy from ATP

Mitochondria DNA mutations: Disorders of the optic nerve (leber’s neuropathy) and other eye defects. Kearns- Sayre Syndrome- abnormal heart rate and central nervous system disorder Mitochondrial myopathy: muscle deterioration, intolerance to exercise