Chromosome Theory PDF

CHROMOSOME THEORY Mendel identified particles of inheritance, but he did not know about chromosomes, meiosis or DNA Morgan- the first to associate a specific gene with a specific chromosome Used fruit fly, Drosophila melanogaster Short generation time Lots of offspring to...

CHROMOSOME THEORY Mendel identified particles of inheritance, but he did not know about chromosomes, meiosis or DNA Morgan- the first to associate a specific gene with a specific chromosome Used fruit fly, Drosophila melanogaster Short generation time Lots of offspring to score FIGURE What is the relationship between genes and chromosomes? 15.01A Pair of Chromosome Genes are located on homologous chromosomes. chromosomes Alleles Maternal cell Paternal cell Chromosomes duplicate Sister before cell division. chromatids of one duplicated During meiosis I, homologous Meiosis I chromosome chromosomes separate and and II alleles segregate. In meiosis II, Egg Sperm sister chromatids separate. Fertilization Each chromosome has one version of a gene (one allele). Maternal Paternal chromosome chromosome Offspring inherit Pair of homologous Homologous chromosomes one allele from chromosomes each have one allele of a each parent. (one from each parent) given gene at the same locus. MORGAN’S EXPERIMENT Isolated white-eyed mutant fly, fig. 15.2 In breeding experiments, found that white eyes were inherited as Mendelian recessive BUT, white eyes could only be found in male offspring in F2 generation, fig. 15.3 FIGURE 15.02 Wild type (red eyes) Mutant (white eyes) FIGURE 15.03A Experiment P × Generation F1 All offspring Generation had red eyes. Results F2 Generation Data from T. H. Morgan, Sex-limited inheritance in Drosophila, Science 32:120–122 (1910).  Conclusion FIGURE w+ w 15.03B P X X Generation X Y w+ × w Sperm Eggs F1 w+ w+ w+ Generation w w+ Sperm Eggs w+ W+ w+ F2 w+ Generation w w w w+ Data from T. H. Morgan, Sex-limited inheritance in Drosophila, Science 32:120–122 (1910). LINKAGE Genes present on same chromosome tend to be inherited together Morgan found the allele for white eyes was linked to the sex chromosomes, sex- linked gene Defective gene present on X chromosome, no copy on shorter Y chromosome, hemizygous, Fig. 15.3 SEX DETERMINATION Scheme varies among organisms, fig. 15.6 In humans, Y chromosome carries few genes In humans, sex-linked genes are usually found on the X chromosome (X-linked) Females only express rec. traits if homozygous Heterozygous females are carriers of that trait FIGURE 15.06 44 + 44 + Parents XY XX 22+ 22+ 22+ X or Y + X Sperm Egg 44 + 44 + 76 + 76 + or ZW XX XY ZZ Zygotes (offspring) (a) The X-Y system (c) The Z-W system 32 16 22 + 22 + (Diploid) (Haploid) XX X (b) The X-0 system (d) The haplo-diploid system FIGURE 15.07 XNXn × XnY Xn Y Sperm Eggs XN XNXn XNY (a) XN XNXn XNY XNXn × XNY XNXn XnY XN Y Sperm Xn Y Sperm Eggs XN XNXn XNY Eggs XN XNXn XNY (b) Xn XNXn XnY (c) Xn XnXn XnY SEX-LINKED TRAITS Humans have a number of sex-linked traits Color blindness Hemophilia Immune system defects https://sites.ualberta.ca/~pletendr/tm-modules/genetics/70gen-hemophil.html MORGAN’S EXPERIMENTS Cross flies differing at two loci, body color and wing shape, Fig. 15.9 Results violate typical Mendelian prediction Body color and wing shape usually inherited together, so must be on same chromosome, linked But some intermediate types were seen FIGURE 15.09A Experiment P Generation (homozygous) Double mutant Wild type (gray × (black body, vestigial body, normal wings) wings) b b vg vg b+ b+ vg+ vg+ F1 dihybrid testcross Homozygous recessive (black Wild-type F1 dihybrid × body, vestigial (gray body, normal wings) wings) b+ b vg+ vg b b vg vg Data from T. H. Morgan and C. J. Lynch, The linkage of two factors in Drosophila that are not sex-linked, Biological Bulletin 23:174–182 (1912). FIGURE 15.09B Experiment Testcross offspring Eggs b+ vg+ b vg b+ vg b vg+ Wild type Black Gray Black (gray normal) vestigial vestigial normal b vg Sperm b+ b vg+vg bb vg vg b+b vg vg bb vg+ vg PREDICTED RATIOS Genes on different : 1 : 1 1 : 1 chromosomes: Genes on same 1 : : : 1 0 0 chromosome: Results 965 : 944 : 206 : 185 Data from T. H. Morgan and C. J. Lynch, The linkage of two factors in Drosophila that are not sex-linked, Biological Bulletin 23:174–182 (1912). RECOMBINATION A new combination of the traits inherited from parents Independent assortment allows recombination of unlinked genes Crossing over allows recombination of linked genes, fig. 15.10 FIGURE 15.10A P generation (homozygous) Wild type (gray body, Double mutant (black body, normal wings) vestigial wings) b+ vg+ b vg b+ vg+ b vg Wild-type F1 dihybrid (gray body, normal wings) b+ vg+ b vg FIGURE F1 dihybrid testcross b+ vg+ b vg Homozygous 15.10B Wild-type F1 recessive dihybrid b vg b vg (black body, (gray body, vestigial wings) normal wings) b+ vg+ b vg b+ vg+ b vg b vg b vg b vg b vg Meiosis I (including crossing over) b+ vg+ Meiosis I and II b+vg b vg+ b vg Recombinant Meiosis II chromosomes b+ vg+ b vg b+ vg b vg+ b vg Eggs Sperm MENDEL RULES WOULD PREDICT b+ vg+ b vg b+ vg b vg+ b vg b+b vg+vg bb vgvg b+b vgvg bb vg+vg ¼ of offspring b+bvg+vg (gray body normal wings) ¼ of offspring bbvgvg (black body vestigial) ¼ of offspring b+bvgvg (gray body vestigial) ¼ of offspring bbvg+vg (black body, normal wings) BUT FIGURE 15.10C Meiosis II Recombinant chromosomes b+ vg+ b vg b+ vg b vg+ Eggs Testcross 965 944 206 185 offspring Wild type Black Gray Black (gray normal) vestigial vestigial normal b vg b+ vg+ b vg b+ vg b vg+ b vg b vg b vg b vg Sperm Parental-type Recombinant offspring offspring Recombination 391 recombinants frequency = × 100 = 17% 2,300 total offspring GENETIC MAPS Can use recombination frequency to get approximate order and distance of genes along a chromosome, fig. 15.11, 15.12 The further apart genes are, the more likely a cross over will occur between them FIGURE 15.11 Results Recombination frequencies 9% 9.5% Chromosome 17% b cn vg FIGURE I 15.12 Y X IV II III Mutant phenotypes Short Maroon Black Cinnabar Vestigial Down- Brown aristae eyes body eyes wings curved eyes wings 0 16.5 48.5 57.5 67.0 75.5 104.5 Long Red Gray Red Normal Normal Red aristae eyes body eyes wings wings eyes (appendages on head) Wild-type phenotypes STRUCTURAL ANOMALIES Deletion- a portion of the chromosome is missing Duplication- a portion of the chromosome has been duplicated, gene dose effects Inversion- portion of chromosome is in reverse orientation Reciprocal translocation- joining fragments of non-homologous chromosomes, fig 15.16 These result from errors in the crossing over process during prophase 1 FIGURE Meiosis I 15.13_3 Nondisjunction Meiosis II Non- disjunction Gametes n+1 n+1 n–1 n–1 n+1 n–1 n n Number of chromosomes (a) Nondisjunction of homo- (b) Nondisjunction of sister logous chromosomes in chromatids in meiosis II meiosis I FIGURE 15.15 FIGURE 15.14 (a) Deletion (c) Inversion A B C D E F G H A B C D E F G H A deletion An inversion removes reverses a a chromosomal segment within segment. a chromosome. A B C E F G H A D C B E F G H (b) Duplication (d) Translocation A B C D E F G H A B C D E F G H M N O P Q R A translocation moves a A duplication segment from one chromosome repeats a segment. to a nonhomologous chromosome. A B C B C D E F G H M N O C D E F G H A B P Q R FIGURE 15.16 Normal chromosome 9 Normal chromosome 22 Reciprocal translocation Translocated chromosome 9 Translocated chromosome 22 (Philadelphia chromosome) IMPRINTING In some cases, expression of trait depends on which parent passed on the allele, fig.15.17 FIGURE Normal Igf2 allele 15.17 Paternal is expressed. chromosome Maternal chromosome Normal-sized mouse Normal Igf2 allele (wild type) is not expressed. (a) Homozygote Mutant Igf2 allele Mutant Igf2 allele inherited from mother inherited from father Normal-sized mouse (wild type) Dwarf mouse (mutant) Normal Igf2 allele Mutant Igf2 allele is expressed. is expressed. Mutant Igf2 allele Normal Igf2 allele is not expressed. is not expressed. (b) Heterozygotes SUMMARY Mendel and Morgan laid the foundation for our understanding of inheritance Together with developments in cytology this established the role of chromosomes as carriers of genetic information But still did not define the molecules of inheritance or the means by which genotype becomes phenotype Chromosomes are composed of DNA and Protein