VII. Mutations: Heritable Changes in Chromosome Number and Structure

- Overview:

VII.Mutations: Heritable Changes in Chromosome Number and Structure - Overview: 1) A mutation is a change in the genome of a cell.

VII.Mutations : Heritable Changes in Chromosome Number and Structure - Overview: 1) A mutation is a change in the genome of a cell. 2) Some mutations occur during DNA repair, or after DNA is damaged by a mutagen. These changes may affect how that particular cell works. When/if that cell divides, then this defect will be propagated to the daughter cells in that body tissue. These are somatic mutations and they only affect that organism’s body.

VII.Mutations : Heritable Changes in Chromosome Number and Structure - Overview: 1) A mutation is a change in the genome of a cell. 2) Some mutations occur during DNA repair, or after DNA is damaged by a mutagen. These changes may affect how that particular cell works. When/if that cell divides, then this defect will be propagated to the daughter cells in that body tissue. These are somatic mutations and they only affect that organism’s body. 3) Some errors occur in DNA replication that precedes cell division; these changes are passed to the daughter cells in that body tissue. These are somatic mutations, too.

VII.Mutations : Heritable Changes in Chromosome Number and Structure - Overview: 1) A mutation is a change in the genome of a cell. 2) DNA repair 3) DNA replication before mitosis 4) Some changes occur during or before gamete formation. These are the heritable mutations that we will focus on.

VII.Mutations : Heritable Changes in Chromosome Number and Structure - Overview: 1) A mutation is a change in the genome of a cell. 2) DNA repair 3) DNA replication before mitosis 4) Some changes occur during or before gamete formation. These are the heritable mutations that we will focus on. 5) Changes occur at FOUR SCALES

VII.Mutations : Heritable Changes in Chromosome Number and Structure - Overview: 1) A mutation is a change in the genome of a cell. 2) DNA repair 3) DNA replication before mitosis 4) Some changes occur during or before gamete formation. These are the heritable mutations that we will focus on. 5) Changes occur at FOUR SCALES - changes in the number of SETS of chromosomes (change in PLOIDY)

VII.Mutations : Heritable Changes in Chromosome Number and Structure - Overview: 1) A mutation is a change in the genome of a cell. 2) DNA repair 3) DNA replication before mitosis 4) Some changes occur during or before gamete formation. These are the heritable mutations that we will focus on. 5) Changes occur at FOUR SCALES - changes in the number of SETS of chromosomes (change in PLOIDY) - changes in the number of chromosomes within a set (ANEUPLOIDY)

VII.Mutations : Heritable Changes in Chromosome Number and Structure - Overview: 1) A mutation is a change in the genome of a cell. 2) DNA repair 3) DNA replication before mitosis 4) Some changes occur during or before gamete formation. These are the heritable mutations that we will focus on. 5) Changes occur at FOUR SCALES - changes in the number of SETS of chromosomes (change in PLOIDY) - changes in the number of chromosomes within a set (ANEUPLOIDY) - changes in the number of genes on a chromosome (DUPLICATIONS/DELETIONS)

VII.Mutations : Heritable Changes in Chromosome Number and Structure - Overview: 1) A mutation is a change in the genome of a cell. 2) DNA repair 3) DNA replication before mitosis 4) Some changes occur during or before gamete formation. These are the heritable mutations that we will focus on. 5) Changes occur at FOUR SCALES - changes in the number of SETS of chromosomes (change in PLOIDY) - changes in the number of chromosomes within a set (ANEUPLOIDY) - changes in the number of genes on a chromosome (DUPLICATIONS/DELETIONS) - changes in the nitrogenous base sequence in a gene

VII.Mutations : Heritable Changes in Chromosome Number and Structure In general, the LARGER the change, the more dramatic (and usually deleterious) the effects. If you have a functioning genome, a big change is going to be MORE LIKELY to disable it than a small change…

VII.Mutation: A. Polyploidy

VII.Mutation: A. Polyploidy 1. Mechanism 1: Failure of meiosis: - there is no reduction; a diploid gamete is produced - typically this will be fertilized by a normal haploid gamete - this typically results in a TRIPLOID zygote… - 50% change in the abundance of proteins produced - usually disrupted development and death of embryo - if it survives, can’t reproduce sexually (odd number) - triploidy is very rare; some animal species are triploid females that reproduce asexually – producing triploid eggs that simply divide on their own and develop into clones of their mother.

VII.Mutation: A. Polyploidy 1. Mechanism 1: Some may still mate with their diploid ‘sibling’ species so that the sperm stimulated the egg to develop – but without incorporation of sperm DNA.) Like this Blue-spotted Salamander A. laterale, which has a triploid sister species, A. tremblayi

VII.Mutation: A. Polyploidy 1. Mechanism 1: 2. Mechanism 2: Failure of Mitosis in Gamete-producing Tissue

2n 1) Consider a bud cell in the flower bud of a plant.

2n 1) Consider a bud cell in the flower bud of a plant. 4n 2) It replicates it’s DNA but fails to divide... Now it is a tetraploid bud cell.

2n 1) Consider a bud cell in the flower bud of a plant. 4n 2) It replicates it’s DNA but fails to divide... Now it is a tetraploid bud cell. 3) A tetraploid flower develops from this tetraploid cell; producing 2n SPERM and 2n EGG

2n 1) Consider a bud cell in the flower bud of a plant. 4n 2) It replicates it’s DNA but fails to divide... Now it is a tetraploid bud cell. 3) A tetraploid flower develops from this tetraploid cell; producing 2n SPERM and 2n EGG 4) If it is self-compatible, it can mate with itself, producing 4n zygotes that develop into a new 4n species. Why is it a new species?

How do we define ‘species’?

A group of organisms that reproduce with one another and are reproductively isolated from other such groups (E. Mayr – ‘biological species concept’)

How do we define ‘species’? Here, the tetraploid population is even reproductively isolated from its own parent species… 4n2n Gametes 2n4n Zygote 2n1n Gametes Zygote 2n3n Triploid is a dead-end… so species are separate

VII.Mutation: A. Polyploidy SO! Polyploidy may be more frequent in plants because they are monoecious more often than animals; especially vertebrates. The only case of polyploidy in animals is usually where triploid females survive and reproduce asexually. Over 50% of all flowering plants are polyploid species; many having arisen by this duplication of chromosome number within a lineage.

VII.Mutation: A. Polyploidy SO! Polyploidy may be more frequent in plants because they are monoecious more often than animals; especially vertebrates. The only case of polyploidy in animals is usually where triploid females survive and reproduce asexually. Over 50% of all flowering plants are polyploid species; many having arisen by this duplication of chromosome number within a lineage. So speciation can be an instantaneous genetic event…

VII.Mutations I: Changes in Chromosome Number and Structure A. Polyploidy B. Aneuploidy

1. Mechanism: Non-disjunction during gamete formation During either Meiosis I or II, segregation of (homologs or sister chromatids) does not occur; both entities are pulled to the same pole.

B. Aneuploidy 1. Mechanism: Non-disjunction during gamete formation During either Meiosis I or II, segregation of (homologs or sister chromatids) does not occur; both entities are pulled to the same pole. This produces gametes with one more (1n + 1) or one less (1n -1) chromosome than they should have. Subsequent fertilization with a normal haploid (1n) gamete produces a trisomy (2n+1) or monosomy (2n-1).

B. Aneuploidy 1. Mechanism: Non-disjunction during gamete formation During either Meiosis I or II, segregation of (homologs or sister chromatids) does not occur; both entities are pulled to the same pole. This produces gametes with one more (1n + 1) or one less (1n -1) chromosome than they should have. Subsequent fertilization with a normal haploid (1n) gamete produces a trisomy (2n+1) or monosomy (2n-1). 2. Human Examples: - There is only one monosomy that survives to birth (Turners’s Syndrome, 45, XO). Why are they so debilitating?

B. Aneuploidy 1. Mechanism: Non-disjunction during gamete formation During either Meiosis I or II, segregation of (homologs or sister chromatids) does not occur; both entities are pulled to the same pole. This produces gametes with one more (1n + 1) or one less (1n -1) chromosome than they should have. Subsequent fertilization with a normal haploid (1n) gamete produces a trisomy (2n+1) or monosomy (2n-1). 2. Human Examples: - There is only one monosomy that survives to birth (Turners’s Syndrome, 45, XO). Why are they so debilitating? There is only one gene for each trait governed by that chromosome. Each chromosome had 1000’s of genes, and there is probably a lethal recessive somewhere in the mix.

B. Aneuploidy 2. Human Examples: - There is only one monosomy that survives to birth (Turners’s Syndrome, 45, XO). - There are several human trisomies that survive to birth:

B. Aneuploidy 2. Human Examples: - There is only one monosomy that survives to birth (Turners’s Syndrome, 45, XO). - There are several human trisomies that survive to birth: Sex Chromsome Trisomies: XXX, XXY (Klinefelter’s Syndrome), XYY – all show a wide range of effects overlapping the normal range (but with lower mean) for intelligence.

B. Aneuploidy 2. Human Examples: - There is only one monosomy that survives to birth (Turners’s Syndrome, 45, XO). - There are several human trisomies that survive to birth: Sex Chromsome Trisomies: XXX, XXY (Klinefelter’s Syndrome), XYY – all show a wide range of effects overlapping the normal range (but with lower mean) for intelligence. Autosomal Trisomies: Patua’s (47, 13+) and Edwards (47, 18+) can survive to birth but have sever effects and early lethality. Down’s (47, 21+), although dramatic, is the LEAST severe.

B. Aneuploidy 2. Human Examples: - There is only one monosomy that survives to birth (Turners’s Syndrome, 45, XO). - There are several human trisomies that survive to birth: Sex Chromsome Trisomies: XXX, XXY (Klinefelter’s Syndrome), XYY – all show a wide range of effects overlapping the normal range (but with lower mean) for intelligence. Autosomal Trisomies: Patua’s (47, 13+) and Edwards (47, 18+) can survive to birth but have sever effects and early lethality. Down’s (47, 21+), although dramatic, is the LEAST severe. Most spontaneous abortuses (>90%) have chromosomal anomalies; most of these are aneuploidy events (and most of those are Turner’s – why?). Obviously, even those individuals that complete development are affected. Apparently, the ADDITION of a chromosome can affect the dosage, activity and regulation of the genes.

VII.Mutation: A. Polyploidy B. Aneuploidy C. Changes in Gene Number and Arrangement

VII.Mutation: A. Polyploidy B. Aneuploidy C. Changes in Gene Number and Arrangement 1. Deletions and Additions:

VII.Mutation: A. Polyploidy B. Aneuploidy C. Changes in Gene Number and Arrangement 1. Deletions and Additions: a. mechanisms: i. unequal crossing over:

VII.Mutation: A. Polyploidy B. Aneuploidy C. Changes in Gene Number and Arrangement 1. Deletions and Additions: a. mechanisms: i. unequal crossing over: If homologs line up askew: A ab B

1. Deletions and Additions: a. mechanisms: i. unequal crossing over: If homologs line up askew: And a crossover occurs as shown: A ab B

1. Deletions and Additions: a. mechanisms: i. unequal crossing over: If homologs line up askew: And a crossover occurs as shown: One chromosome will have the A locus duplicated, and the other will have the A locus deleted: Aab B

1. Deletions and Additions: a. mechanisms: i. unequal crossing over: (both) ii. Transposons (addition) - transposons are copied (replicated) independent of the S phase of interphase…the copy is inserted elsewhere in the genome. Genes can ‘tag along’, and be replicated and inserted elsewhere, increase the copy number for that gene (duplication).

1. Deletions and Additions: a. mechanisms: i. unequal crossing over: (both) ii. Transposons (addition) - transposons are copied (replicated) independent of the S phase of interphase…the copy is inserted elsewhere in the genome. Genes can ‘tag along’, and be replicated and inserted elsewhere, increase the copy number for that gene (duplication). OR, a transposon can be inserted within a gene, destroying it and functionally ‘deleting’ it.

1. Deletions and Additions: a. mechanisms: b. effects: - deletions are usually bad, because the loss of one gene can reveal lethal recessives at the locus or disrupt concentrations of protein. Of course, they are typically not as bad as the loss of an entire chromosome with 1000’s of genes, right?

1. Deletions and Additions: a. mechanisms: b. effects: - deletions are usually bad, because the loss of one gene can reveal lethal recessives at the locus or disrupt concentrations of protein. - duplications can be bad, as they can disrupt protein concentrations. However, duplications can also be very GOOD for two reasons:

1. Deletions and Additions: a. mechanisms: b. effects: - deletions are usually bad, because the loss of one gene can reveal lethal recessives at the locus or disrupt concentrations of protein. - duplications can be bad, as they can disrupt protein concentrations. However, duplications can also be very GOOD for two reasons: 1) more is sometimes better (rRNA or melanin examples); with more DNA copies of a gene, more RNA and protein can be made.

1. Deletions and Additions: a. mechanisms: b. effects: - deletions are usually bad, because the loss of one gene can reveal lethal recessives at the locus or disrupt concentrations of protein. - duplications can be bad, as they can disrupt protein concentrations. However, duplications can also be very GOOD for two reasons: 1) more is sometimes better (rRNA, melanin example); with more DNA copies of a gene, more RNA and protein can be made. 2) a copy can act as a source of new genes (Ohno Hypothesis).

1. Deletions and Additions: a. mechanisms: b. effects: - deletions are usually bad, because the loss of one gene can reveal lethal recessives at the locus or disrupt concentrations of protein. - duplications can be bad, as they can disrupt protein concentrations. However, duplications can also be very GOOD for two reasons: 1) more is sometimes better (rRNA, melanin example); with more DNA copies of a gene, more RNA and protein can be made. 2) a copy can act as a source of new genes (Ohno Hypothesis). One of the major caveats of evolution was “how are new genes formed?” If an old gene is changed to something new, well that’s fine but you have now LOST the original function… how does evolution ADD (rather than substitute) information?

1. Deletions and Additions: a. mechanisms: b. effects: - deletions are usually bad, because the loss of one gene can reveal lethal recessives at the locus or disrupt concentrations of protein. - duplications can be bad, as they can disrupt protein concentrations. However, duplications can also be very GOOD for two reasons: 1) more is sometimes better (rRNA, melanin example); with more DNA copies of a gene, more RNA and protein can be made. 2) a copy can act as a source of new genes (Ohno Hypothesis). One of the major caveats of evolution was “how are new genes formed?” If an old gene is changed to something new, well that’s fine but you have now LOST the original function… how does evolution ADD (rather than substitute) information? By duplicating genes that work, then modifying them by mutation and creating a new gene with a new function without losing the original. Mutations that stop gene function have no effect (because the original is still there), but mutations that change a gene into another beneficial sequence can still have a positive effect and be selected for.

1. Deletions and Additions: a. mechanisms: b. effects: - Ohno’s hypothesis predicts that there will be genes that do different things, but that have a very similar structure (suggesting their common gene ancestry). These are gene families, and they are common. It definitely appears that this is how new genetic information is produced and then modified.

VII.Mutation: A. Polyploidy B. Aneuploidy C. Changes in Gene Number and Arrangement 1. Deletions and Additions: 2. Inversions:

C. Changes in Gene Number and Arrangement 1. Deletions and Additions: 2. Inversions: Loop cut, then loop reattaches…

C. Changes in Gene Number and Arrangement 1. Deletions and Additions: 2. Inversions: Problem – no longer homologous along length

C. Changes in Gene Number and Arrangement 1. Deletions and Additions: 2. Inversions: Problem – no longer homologous along length Solution – inversion loop

C. Changes in Gene Number and Arrangement 1. Deletions and Additions: 2. Inversions: Solution – inversion loop Effect – cross-overs are non-functional

C. Changes in Gene Number and Arrangement 1. Deletions and Additions: 2. Inversions: Solution – inversion loop Effect – cross-overs are non-functional

C. Changes in Gene Number and Arrangement 1. Deletions and Additions: 2. Inversions: Solution – inversion loop Effect – cross-overs are non-functional Net effect: stabilizes sets of genes. This allows selection to work on groups of alleles… those that work well TOGETHER are selected for and can be inherited as a ‘co- adapted gene complex’

VII.Mutation: A. Polyploidy B. Aneuploidy C. Changes in Gene Number and Arrangement 1. Deletions and Additions: 2. Inversions: 3. Translocations:

END OF MATERIAL FOR EXAM 2

3. Translocations: Transfer, exchange, or fusion of DNA between non-homologous chromosomes.

VII.Mutation: A. Polyploidy B. Aneuploidy C. Changes in Gene Number and Arrangement D. Changes in Nitrogenous Base Sequence

VII.Mutation: A. Polyploidy B. Aneuploidy C. Changes in Gene Number and Arrangement D. Changes in Nitrogenous Base Sequence 1. Substitutions: The wrong base is laid down opposite the template. - effects may be: - silent: no change in the AA sequence (occurs in intron or does not change a codon… AAA to AAG both code for lysine.) - at most will change a single Amino Acid (good, bad, or neutral)

VII.Mutation: A. Polyploidy B. Aneuploidy C. Changes in Gene Number and Arrangement D. Changes in Nitrogenous Base Sequence 1. Substitutions: The wrong base is laid down opposite the template. - effects may be: - silent: no change in the AA sequence (occurs in intron or does not change a codon… AAA to AAG both code for lysine.) - at most will change a single Amino Acid (good, bad, or neutral) 2. Addition/Deletion: A base is skipped or added incorrectly - effects: - changes the entire three-base sequence from that change to the end of the exon. Changes every amino acid from this position on in that exon. - effects are typically dramatic, resulting in lack of function