Development of chromosome theory of inheritance 1900 rediscovery

Development of chromosome theory of inheritance • ~1900 “rediscovery” of Mendel’s work • 1902 similarity of mendelian transmission and chromosome behavior in mitosis & meiosis (T. Boveri; W. Sutton) • 1905 observations of sex-limited heteromorphic chromosomes (N. Stevens) • 1910 discovery of sex-linked gene (T. H. Morgan) • 1916 sex chromosome non-disjunction proof (C. Bridges)

Development of chromosome theory of inheritance • ~1900 “rediscovery” of Mendel’s work • 1902 similarity of mendelian transmission and chromosome behavior in mitosis & meiosis (T. Boveri; W. Sutton) • 1905 observations of sex-limited heteromorphic chromosomes (N. Stevens) • 1910 discovery of sex-linked gene (T. H. Morgan) • 1916 sex chromosome non-disjunction proof (C. Bridges) replication mitosis Fig. 3 -1 replication meiosis

Drosophila melanogaster has a heteromorphic chromosome pair • Males have one of each member (XY) • Females have two of one member of the pair (XX) Fig. 3 -5

Morgan’s white gene analysis white-eye male F 1 F 2 X red-eye female all red-eye ½ males white-eye all females red-eye red = w+ allele (wildtype) white = w allele (mutant)

Morgan’s white gene analysis Reciprocal cross white-eye male X red-eye female red-eye male X white-eye female F 1 all red-eye F 1 all males white-eye all females red-eye F 2 ½ males red-eye ½ males white-eye ½ females red-eye ½ females white-eye Sex-dependent transmission & expression (sex-linkage)

Morgan’s white gene analysis - INTERPRETATION Reciprocal cross white-eye male Xw/Y X red-eye female Xw+/Xw+ F 1 all red-eye Xw+/Y Xw/Xw+ F 2 ½ males red-eye Xw+/Y ½ males white-eye Xw/Y all females red-eye Xw+/Xw+ red-eye male Xw+/Y X white-eye female Xw/Xw F 1 all males white-eye Xw/Y all females red-eye Xw/Xw+ F 2 ½ males red-eye Xw+/Y ½ males white-eye Xw/Y ½ females red-eye Xw+/Xw ½ females white-eye Xw/Xw Sex-linkage indicates locus on a sex-limited chromosome

Sex linkage can be the reverse (e. g. , lepidopterans, birds) Females have the heteromorphic chromosome pair (ZW) • Are the heterogametic sex Fig. 3 -6 Males are ZZ • Are the homogametic sex

C. Bridges’ cross of red males (w+/Y) and white females (w/w) produced rare • white female (must be w/w = gets two X chromosomes from mother? ) • red male (must be w+) = gets father’s X chromosome?

C. Bridges’ cross of red males (w+/Y) and white females (w/w) produced rare • white female (must be w/w = gets two X chromosomes from mother? ) • red male (must be w+) = gets father’s X chromosome? Explanation: chromosome nondisjunction Fig. 3 -7 • Confirmed chromosome theory • Discovered general class of rare, recurring mutation with significant consequences • Demonstrated why geneticists should “treasure your exceptions”

The sizes and densities of genes differs considerably among organisms Fig. 3 -13 Due to: spacing between genes introns, relative number and sizes other stuff

Genic organization of two small regions of human chromosome 21 Fig. 3 -12

Karyotype of Indian muntjac (2 n+6) Fig. 3 -8

Conventional cytogenetic markers for karyotype analysis • Chromosome number (n, 2 n, etc. )

Conventional cytogenetic markers for karyotype analysis • Chromosome number (n, 2 n, etc. ) • Chromosome size (large → small) • Centromere location: central (metacentric) terminal (telocentric) in-between (acrocentric) • Chromatin differential compaction • Euchromatin (lightly staining, lower density of DNA, most genes) • Heterochromatin (densely staining, highly compacted, usually centromeric) • Banding patterns (localized, alternating high/low compaction regions)

Human karytype (female) using G-banding technique Fig. 3 -17

Drosophila karyotype in diploid and polytene cells (larval salivary gland cells) Fig. 3 -18

Conventional cytogenetic markers for karyotype analysis • Chromosome number (n, 2 n, etc. ) • Chromosome size (large → small) • Centromere location: central (metacentric) terminal (telocentric) in-between (acrocentric) • Chromatin differential compaction • Euchromatin (lightly staining, lower density of DNA, most genes) • Heterochromatin (densely staining, highly compacted, usually centromeric) • Banding patterns (localized, alternating high/low compaction regions) • Special structures (nucleolus organizers, constrictions) Stylized corn chromosomes Fig. 3 -19

In situ hybridization with a fluorescently labelled probe for a single-copy muscle protein gene Fig. 3 -11

In situ hybridization with a 3 H-labelled probe for a mouse satellite DNA Fig. 3 -14

In situ hybridization with a fluorescently labelled telomeric DNA sequence (human fibroblast) Fig. 3 -16

Repeated from Cell Biology (must read/review) Pages 88 -90: chromosome/chromatin structure Pages 90 -95: mitosis & meiosis Pages 96 -97: life cycles of haploid and diploid organisms

Overview of allele transmission through mitosis and meiosis Fig. 3 -35

Overview of allele transmission through chromatid formation/ DNA replication Fig. 3 -36

Euglena genomes • nuclear (red) • mitochondrial (yellow) Fig. 3 -40

Fig. 3 -41

Neurospora nuclear (ad) and mitochondrial (poky) genes display distinctive sexual transmission patterns (maternal inheritance) Fig. 3 -42

Organellar genes can show cytoplasmic segregation during asexual growth Fig. 3 -43

Typical inheritance of a human mitochondrial disease Fig. 3 -45

Fig. 3 -1