LECTURE 4SEX DETERMINATION AND X-LINKED INHERITANCE;CHROMOSOMAL BASIS OF INHERITANCE;Reading: Chapter 7.2, 7.3.; Chapter 4.11.; Chapter 3.5. Chapter 7.1. Homework: Ch 7 Q: 7, 10. ; Chapter: 4 Q 23, 25, 30, 33, 44. ; Chapter 3 Q 10, 11, 33.-> Q33 is a historical observation that supported the chromosome theory of inheritance. But does the description make complete sense?A. Sex determination 1. The XY system (mammals, some plants)Y chromosome determines maleness2. The X/A system (Drosophila and some other insects) ratio of X-chromosomes to sets of autosomes X/A=1->female; X/A=0.5->male 3. Other casesThe ZW system (birds, some insects)The haplodiploid system (bees)Haploids: mating type [1 gene (+ x -) or multiple genes (A1B1 x A2B3)]. Q: Assume that a female fly (XX) generates a few gametes after non-disjunction of the X-chromosomes, resulting in eggs with two X’s (XX) and eggs with no X (O). 1. The XX egg is fertilized by a Y sperm. What is the genotype of the fly?2. The O egg is fertilized by an X sperm. What is the genotype of the progeny?B. Sex (X)-linked inheritance1. Thomas H Morgan’s white-eyed fruit fly DrosophilaData: Sex is linked to eye-color phenotype.Interpretation:The eye color gene 'white' resides on the X. The Y chromosome doesn't have a corresponding allele. Males are hemizygous. 2. Reciprocal crossesNote the crisscross pattern between sex and phenotype. 3. X-chromosomal genes in humansEx: Red-green color blindness; hemophilia (Queen Victoria’s family), Duchenne muscular dystrophyX-chromosomal genes are inherited in a sex-linked fashion, while genes on chr 1-22 (the autosomes) are autosomally inherited (speak: normally).4. Very rare exceptions:a) pseudoautosomal inheritance. A few genes are present on both X and Y. b) Y-specific genes. Ex: the SRY-gene for Testis Determining Factor (male).5. How to recognize sex (X)-linked recessive traits in human pedigreesmostly observed in males, trait never passes from father to sonmostly inherited via heterozygous females, 'carriers' are always femaleC. Chromosome theory of inheritance: Boveri and Sutton (1902), after the rediscovery of Mendel's laws in 1900, collected evidence indicating that...1. Statement: Chromosomes carry the genetic material.Pairs of chromosomes correspond to Mendel's paired 'unit factors'/genes.2. Evidence - Like genes, chromosomes are inherited from Mom and Dad in equal proportions.- Like genes, chromosomes alternate between diploid and haploid phases. Gametes contain half the number of chromosomes and half the number of Mendelian alleles compared to regular (diploid) cells. - Like genes, chromosomes segregate independently during meiosis. Independent assortment of chromosomes in metaphase I corresponds to independent assortment of alleles in Mendel's dihybrid cross (1913: Elinor Carothers, grasshopper). - Sex is determined and inherited via special chromosomes (1905: Nettie Stevens)- Correlation between cytogenetics of sex determination (XY versus ZW systems) and sex-linkage of inheritance (e.g. human versus chicken).- Calvin Bridges (1914) explained ‘exceptional’ white-eyed flies on the basis of meiotic non-disjunction (mentioned, but not explained in Klug). Later: D. Maternal (cytoplasmic) inheritanceDefinition: Trait is transmitted only through the female lineage (egg). Indicator: Reciprocal crosses yield different results.Traits may segregate during mitotic/somatic cell division -> clonal sectors, variegation.Genes located on the mitochondrial genome (only 17kb in human, ~20 genes)Genes located on the plastid (chloroplast) genome (~150kb in plants)Note: Mt and cp typically have high gene dosage per cell (>10 copies per cell)Genes do not segregate through meiosis/mitosisRelevance: Rare neurological and muscle wasting diseases; Mt DNA is a marker for female lineage (‘Eve’ lived 200,000 years ago), evidence for ‘reproductive