1 Chapter 11 - Chromosome Mutations Questions to be considered: 1) how are changes in chromosome number (different from haploid or diploid) defined? 2) how do changes in chromosome number occur? 3) what are the meiotic consequences of changes in chromosome number? 4) what are the phenotypic consequences of changes in chromosome number? 5) How do changes in chromosomes structure affect meiotic pairing? 6) How do changes in chromosome structure affect recombination frequency? Terminology: ploidy: number of chromosomes in an organism relative to a set of homologues euploidy: having a multiple of a complete set of homologues aneuploidy: having an incomplete set of homologues monoploid: a cell having only one chromosome set (usually an aberration), or an organism composed of such cells (a set of homologues = x) diploid: a cell having two chromosome sets, or an individual having two sets of chromosomes sets in each of its cells (two monoploid sets = 2x) triploid: a cell having three chromosome sets, or an organism composed of such cells (three monoploid sets = 3x) polyploid: a cell having three or more chromosome sets, or an organism composed of such cell (greater than 2x) autopolyploidy: all sets of chromosomes originate from the same species
2 allopolyploidy: some sets of chromosomes originate from different species nondisjunction: the failure of homologues (at meiosis) or sister chromatids (at mitosis) to separate properly to opposite poles monosomic: a cell or individual that is basically diploid but that has only one copy of one particular chromosome type and thus has chromosome number 2n-1 nullisomic: a cell or individual with one chromosomal type missing, with a chromosome number such as n - 1 or 2n - 2 trisomic: basically a diploid with an extra chromosome of one type, producing a chromosome number of the form 2n + 1 In polyploids x is not equivalent to n (see table 8-1) x= a set of chromsomes with one member of all homologous pairs example - wheat is a hexaploid (6x) = 42 chromosomes (x = 7) - haploid number (chromosomes in gamete) = 21 Examples of Changes in Ploidy MONOPLOID - males of bees and wasps - gametes produced by mitosis - generation of plants from pollen - select for mutations in a monoploid (which is sterile) - double the chromosome number using colchicine POLYPLOIDS 1) autopolyploids all sets of chromsomes are from the same species 2) allopolyploids sets of chromosomes are from different species
3 Triploids - usually sterile (commercially developed bananas, oysters) - meiotic pairing possibilities: 1) all three chromosomes form a group = TRIVALENT 2) two chromosomes pair (BIVALENT) and one chromosome is unpaired (UNIVALENT) Pairing Possibilities TRIVALENT BIVALENT UNIVALENT (refer to Figure 11-5) - two chromosomes move to one pole, one chromosome moves to the other pole - for each chromosome trio, there what chance of one chromosome moving to a given pole? results: if there are x chromosomes, the chance of one chromosome from each trio going to the same pole is 1/2 x-1 - if x = 8, p(normal gamete) = 1/128 conclusions: most gametes are aneuploid AUTOTETRAPLOID (two sets of identical chromosomes)
4 (refer to Figure 11-7) segregation - prediction requires a stable pairing pattern e.g. assume bivalent pairing in an individual of genotype aaaa (a is closely linked to the centromere) question: what is the probability of progeny of genotype aaaa (the recessive phenotype)?
5 Pairing Gametes Produced by Random Spindle Attachment 1 2 A A 1 + 3 Aa 2 + 4 Aa 1 2 3 4 A A a a 3 4 1 3 2 4 a a A a A a 1 + 4 Aa 2 + 3 Aa 1 + 2 AA 3 + 4 aa 1 + 4 Aa 2 + 3 Aa 1 4 A a 1 + 2 AA 3 + 4 aa 2 3 A a 1 + 3 Aa 2 + 4 Aa conclusion: p(aaaa) = = ALLOPOLYPLOIDS (multiple chromosome sets from different species) e.g. radish (n1 = 9) x cabbage (n2 = 9) (Figure 11-8) The Evolution of Wheat (an allopolyploid) (Figure 11-10) ANEUPLOIDS (missing part of a chromosome set) - generated through nondisjunction (chromosomes do not segregate at Meiosis I or chromatids do not separate at Meiosis II) (Figure 11-13) --------> n + 1 and n - 1 gametes Monosomic: only one copy of a chromosome is present - 2n - 1 (n - 1 gamete + n gamete) Nullisomic: has no copy of a chromosome
6-2n - 2 = (n -1 + n-1 gametes) Trisomic: has an extra copy of a chromosome - 2n + 1 = (n + 1 + n) Human Aneuploids - autosomal aneuploids are mostly lethal - sex chromosome aneuploids are tolerated examples: 1) Turner Syndrome (XO) - monosomic for sex chromosome - occurrence = 1/2000 live births - PHENOTYPE: sterile females that are short in stature - X chromosome may come from the father or mother (Figure 11-14) 2) Klinefelter Syndrome (XXY) - trisomic for sex chromosomes - occurrence = 1/1000 live births - PHENOTYPE: sterile males (FIGURE 11-16) 3) Down Syndrome - trisomy 21 (autosomal) - occurrence = 15/10 000 live births (related to age of mother) (FIGRUE 11-17) - other chromosomal abnormalities are produced - 7.5% of conceptions are spontaneously aborted due to chromosomal abnormalities CHROMOSOMAL REARRANGEMENTS Types of rearrangements:
7 Balanced: no DNA is lost or gained, only gene arrangement is altered e.g. inversions and translocations Imbalanced DNA is lost or gained, e.g. deletions and duplications - caused by chromosome breakage (e.g. induced by ionizing radiation) and rejoining of fragments in an altered configuration (Figure 11-19A) - caused by crossing-over between repetitive DNA (Figure 11-19B) 1. Deletion: removal of a chromosomal segment from a chromosome set characteristics: 1) following a deletion, chromosome is shortened 2) often lethal when homozygous (maintained as heterozygote) 3) during prophase I, heterozygous individuals form a deletion loop (Figure 11-21, 11-28) b a c d e A C D E 4) heterozygotes show reduced recombination A C D E a b c d e - there is NO recombination within a deleted region if a-c distance is normally 10 map units (i.e. the frequency of recombination = 10%) and a deletion heterozygote has an a-c recombination frequency of 3%, then a deletion of 7 map units (including b) has occurred
8 5) pseudodominance of recessive alleles in heterozygotes Example: An individual is heterozygous for a deletion involving Bar-eyed gene in Drosophila (i.e. it has reduced eyes). The homozygous condition is lethal. How much of the chromosome is missing? Approach: Cross individual heterozygous for the deletion to an individual homozygous for recessive mutations near Bar gene (an example is forked) Bar eye B F? del F X B f B f Phenotype bar-eyed, wild type wild type, forked Conclusion: if a recessive mutation appears dominant (pseudodominance) when heterozygous with a deletion, the gene must be included within the deletion
9 If a series of deletions spanning known regions is available, a recessive mutation can be mapped by combining it with each deletion and determining with which it appears pseudodominant (Figure 11-29) Example: A recessive mutation (c) causes curled wings in Drosophila. The C gene is found on chromosome 1 cc = curled wings C_ = wild type wings Approach: cross to a series of lines heterozygous for deletions in different regions of chromosome 1 Result: F1 is heterozygous for deletion and c - if F1 shows curled phenotype, pseudodominance is displayed and the deletion therefore includes C -therefore, C is in the region Duplications -a region of a chromosome is copied elsewhere
10 - duplicate copies, allow divergence of one copy from its original function ---> gene family adjacent duplications pairing in duplication heterozyg -3 copies (2 in one chromosome, one in homologue) 1) between adjacent regions 2) between different chromosomes Inversions -chromosome broken (= breakpoint) and rejoined in opposite orientation
11 - information isn t lost, therefore no consequences to homozygous individual unless the breakpoint interrupts a gene (Figure 11-20) paracentric - inversion excludes centromere original A B C D E paracentric inversion A D C B E pericentric - inversion includes centromere original A B C D pericentric inversion A C B D Meiosis in inversion heterozygotes (Figure 11-21 Case 1 - heterozygous for a paracentric inversion A B C D E A D C B E Consequences: 1) meiosis in an individual heterozygous for a paracentric inversions (see figure 8-22)
12 Consequences -recombination within the inversion loop produces acentric and dicentric recombinant chromosomes -acentric chromosome is lost -dicentric chromosome is broken causing deletions - inviable -no recombinant products are viable therefore, recombinants produced within the inversion = therefore, apparent distance between inversion breakpoints = experiment: cross a plant with dominant alleles at 5 genes to a plant with recessive alleles at 5 genes, which also carries a paracentric inversion cross the F1 heterozygote to a recessive homozygote (test cross)
13 A B C D E a d c b e A B C D E x a d c b e 5 5 5 5 5 5 5 5 5 5 A B C D E F1 heterozygote a d c b e Results: percentage of recombinants between pairs of genes seen in the test cross progeny A B C D E A 0 8 8 8 12 B 0 0 0 4 C 0 0 4 D 0 4 E 0 Conclusions:
14 Case 2 -Meiosis in an individual heterozygous for a pericentric inversion (Figure 11-23) 2) pericentric inversions -recombination within the inversion loop generates duplications and deletions -gametes carrying these recombinants are inviable, or produce inviable zygotes (reduced fertility) -recombinants produced within the inversion = 0, distance between breakpoints = 0
15 Translocations -reciprocal translocation: a segment of one chromosome is exchanged with a segment from a nonhomologous chromosome -as with inversions, may be no phenotypic consequences to the homozygous individual -heterozygotes will have reduced fertility due to abnormal chromosome pairing and segregation
16 24 Figure 11- segregation at meiosis produces: 1) two normal chromosomes (N1 + N2) - viable 2) two translocated chromosomes (T1 + T2) - viable 3) T1 + N1 - inviable 4) T2 + N2 - inviable -events are equally likely, therefore 50% of gametes are inviable = semisterile