Heredity, Gene Regulation, and Development Mutation A. Overview.

Heredity, Gene Regulation, and Development MutationA. Overview

MutationA. Overview

1) A mutation is a change in the genome of a cell.

MutationA. Overview

1) A mutation is a change in the genome of a cell. 2) Somatic Mutations:

- can occur during DNA replication prior to mitosis - can occur during DNA repair - can be caused by exposure to a mutagen - if uncorrected, can be passed to daughter cells. - typically not the source of heritable mutations

MutationA. Overview

1) A mutation is a change in the genome of a cell. 2) Somatic Mutations:

- can occur during DNA replication prior to mitosis - can occur during DNA repair - can be caused by exposure to a mutagen - if uncorrected, can be passed to daughter cells. - typically not the source of heritable mutations

3) Germ-line Mutations:- occur in germ-line cells (tissues that produce gametes or

spores)- occur so early in development, before germ-line cells have differentiated, that they affect germ-line cells.- occurs in DNA replication or meiosis, producing mutant

gametes/spores

VI. MutationA.Overview

3) These “changes in a genome” can occur at four scales of genetic organization:

- Change in the number of sets of chromosomes ( change in ‘ploidy’)

- Change in the number of chromosomes in a set (‘aneuploidy’)

- Change in the number and arrangement of genes on a chromosome(gene duplications, deletions, inversions, translocations)

- Change in the nitrogenous base sequence within a gene(point mutations)

Typically, the larger the change, the more dramatic (and negative) the result

VI. MutationA.OverviewB.Changes in Ploidy

- These are the most dramatic changes, adding a whole SET of chromosomes

Triploidy occurs in 2-3% of all human pregnancies, but almost always results in spontaneous abortion of the embryo.

Some triploid babies are born alive, but die shortly after.

Syndactyly (fused fingers), cardiac, digestive tract, and genital abnormalities occur.

1.Mechanism #1: Complete failure of Meiosis - if meiosis fails, reduction does not occur and a diploid gamete is produced. This can occur because of failure of homologs OR sister chromatids to separate in Meiosis I or II, respectively.

Failure of Meiosis I

2n = 4Gametes:2n = 4

1.Mechanism #1: Complete failure of Meiosis - if meiosis fails, reduction does not occur and a diploid gamete is produced. This can occur because of failure of homologs OR sister chromatids to separate in Meiosis I or II, respectively.

Failure of Meiosis II

2n = 4

Normal gamete formation is on the bottom, with 1n=2 gametes. The error occurred up top, with both sister chromatids of both chromosomes going to one pole, creating a gametes that is 2n = 4.

1.Mechanism #1: Complete failure of Meiosis - if meiosis fails, reduction does not occur and a diploid gamete is produced. This can occur because of failure of homologs OR sister chromatids to separate in Meiosis I or II, respectively. - this results in a single diploid gamete, which will probably fertilize a normal haploid gamete, resulting in a triploid offspring.

-negative consequences of Triploidy:1) quantitative changes in protein production and developmental regulation.2) can’t reproduce sexually; can’t produce gametes if you are 3n.

1) quantitative changes in protein production and regulation.2) can’t reproduce sexually; can’t produce gametes if you are 3n.3)

Aspidoscelis uniparens is a species that consists of 3n females that reproduce clonally – laying 3n eggs that divide without fertilization. It evolved from the diploid species, A. inornata

some organisms can survive, and reproduce parthenogenetically (eggs by mitosis… offspring are clones).

1.Mechanism #1: Complete failure of Meiosis2.Mechanism #2: Failure of Mitosis in Gamete-producing Tissue

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

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; eventually 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…So speciation can be an instantaneous genetic event…

Gametes

Zygote

Gametes

Zygote

Triploid is a dead-end… so species are separate

1.Mechanism #1: Complete failure of Meiosis2.Mechanism #2: Complete failure of Mitosis3.Mechanism #3: Allopolyploidy - hybridization

2n = 16

Black Mustard

2n = 18

Cabbage

gametes

n = 17

Fertilization produces a cell with non-homologous chromosomes

2n = 34

Polyploidy occurs here; creating a cell with homologous sets

New Species

Spartina alterniflora from NA colonized Europe

Spartina maritima native to Europe

Spartina anglica – an allopolyploid and a worldwide invasive outcompeting native species

Sterile hybrid – Spartina x townsendii

Allopolyploidy – 1890’s

1.Mechanism #1: Complete failure of Meiosis2.Mechanism #2: Complete failure of Mitosis3.Mechanism #3: Allopolyploidy - hybridization4.The Frequency of Polyploidy

For reasons we just saw, we might expect polyploidy to occur more frequently in hermaphroditic species, because the chances of ‘jumping’ the triploidy barrier to reproductive tetraploidy are more likely. Over 50% of all flowering plants are polyploid species; many having arisen by this duplication of chromosome number within a lineage.

VI. MutationA.OverviewB.Changes in PloidyC.Changes in ‘aneuploidy’ (changes in chromosome number)

1. Mechanism: Non-disjunction (failure of a homologous pair or sister chromatids to separate)

1. Mechanism: Non-disjunction (failure of a homologous pair or sister chromatids to separate)2. Human Examples

a. trisomiesTrisomy 21 – “Downs’ Syndrome”

Trisomy 18 – Edward’s Syndrome

Trisomy 13 – Patau Syndrome

Trisomy 9

Trisomy 8

Trisomy 22

Trisomy 16 – most common – 1% of pregnancies – always aborted

Some survive to birth

a. trisomies47, XXY – “Klinefelter’s Syndrome”

Extreme effects listed below; most show a phenotype within the typical range for XY males

a. trisomies47, XXX – “Triple-X Syndrome” No dramatic effects on the

phenotype; may be taller.

In XX females, one X shuts down anyway, in each cell (Barr body).

In triple-X females, 2 X’s shut down.

a. trisomies47, XYY – “Super-Y Syndrome” Often taller, with scarring

acne, but within the phenotypic range for XY males

b. monosomies45, XO– “Turner’s Syndrome” (the only human monosomy to survive to birth)

VI. MutationA.OverviewB.Changes in PloidyC.Changes in ‘Aneuploidy’ (changes in chromosome number)D. Change in Gene Number/Arrangement

1. Mechanism #1: Unequal Crossing-Over

a. process:

If homologs line up askew:

a. process:

If homologs line up askewAnd a cross-over occurs

a. process:

If homologs line up askewAnd a cross-over occurs Unequal pieces of DNA will be exchanged… the A locus has been duplicated on the lower chromosome and deleted from the upper chromosome

a. process: b. effects:

- can be bad:deletions are usually bad – reveal deleterious recessivesadditions can be bad – change protein concentration

- can be good:more of a single protein could be advantageous (r-RNA genes, melanin genes, etc.)

source of evolutionary novelty (Ohno hypothesis - 1970)where do new genes (new genetic information) come from?

Gene A Duplicated A

Mutation – may even render the proteinnon-functional

But this organism is not selected against, relative to others in the population that lack the duplication, because it still has the original, functional, gene.

generations

Mutation – may even render the proteinnon-functional

Mutation – other mutations may render the protein functional in a new way

So, now we have a genome that can do all the ‘old stuff’ (with the original gene), but it can now do something NEW. Selection may favor these organisms.

Gene A Duplicated A

generations

If so, then we’d expect many different neighboring genes to have similar sequences. And non-functional pseudogenes (duplicates that had been turned off by mutation).These occur – Gene Families

And, if we can measure the rate of mutation in these genes, then we can determine how much time must have elapsed since the duplication event…

Gene family trees…

1.Mechanism #1: Unequal Crossing-Over2.Mechanism #2: Inversion (changes the order of genes on a chromosome)

Chromosomes are no longer homologous along entire length

B-C-D on topd-c-b on bottom

Chromosomes are no longer homologous along entire length

ONE “loops” to get genes across from each other…

And if a cross-over occurs….

The cross-over products are non-functional, with deletions AND duplications

The only functional gametes are those that DID NOT cross over – and preserve the parental combination of alleles

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’

1.Mechanism #1: Unequal Crossing-Over2.Mechanism #2: Inversion (changes the order of genes on a chromosome)3.Mechanism #3: Translocation (gene or genes move to another homologous set)

Translocation Downs.

Transfer of a 21 chromosome to a 14 chromosome

Can produce normal, carrier, and Down’s child.

VI. MutationA.OverviewB.Changes in PloidyC.Changes in ‘Aneuploidy’ (changes in chromosome number)D. Change in Gene Number/ArrangementE. Change in Gene Structure

1.Mechanism #1: Exon Shuffling

Crossing over WITHIN a gene, in introns, can recombine exons within a gene, producing new alleles.

EXON 1a EXON 2a EXON 3a Allele “a”

EXON 1A EXON 2A EXON 3A Allele “A”

VI. MutationA.OverviewB.Changes in PloidyC.Changes in ‘Aneuploidy’ (changes in chromosome number)D. Change in Gene Number/ArrangementE. Change in Gene Structure

1.Mechanism #1: Exon Shuffling

Crossing over WITHIN a gene, in introns, can recombine exons within a gene, producing new alleles.

EXON 1a EXON 2a EXON 3a Allele “a”

EXON 1A EXON 2A EXON 3A Allele “A”

EXON 2a EXON 3aEXON 1A

EXON 2A EXON 3AEXON 1a

Allele “α”

Allele “ά”

Throws off every 3-base codon from mutation point onward

VI. MutationA.OverviewB.Changes in PloidyC.Changes in ‘Aneuploidy’ (changes in chromosome number)D. Change in Gene Number/ArrangementE. Change in Gene Structure 1. Mechanism #1: Exon Shuffling 2. Mechanism #2: Point Mutations

a. addition/deletion: “frameshift” mutations

…T C C G T A C G T ….

Normal

…A G G C A U G C A …

ARG HIS ALA

Mutant: A inserted

…T C C A G T A C G T ….

…A G G U C A U G C A …

ARG SER CYS

VI. MutationA.OverviewB.Changes in PloidyC.Changes in ‘Aneuploidy’ (changes in chromosome number)D. Change in Gene Number/ArrangementE. Change in Gene Structure 1. Mechanism #1: Exon Shuffling 2. Mechanism #2: Point Mutations

a. addition/deletion: “frameshift” mutationsb. substitution

At most, only changes one AA (and may not change it…)

… T C C G T A C G T ….

Normal

…A G G C A U G C A …

ARG HIS ALA

Mutant: A for G

…T C C A T A C G T ….

…A G G U A U G C A …

ARG TYR ALA

VI. MutationA.OverviewB.Changes in PloidyC.Changes in ‘Aneuploidy’ (changes in chromosome number)D. Change in Gene Number/ArrangementE. Change in Gene StructureF. Summary

Sources of Variation Causes of Evolutionary Change

MUTATION: Natural Selection -New Genes: point mutation Mutation (polyploidy can make new exon shuffling species)

RECOMBINATION: - New Genes: crossing over -New Genotypes: crossing over independent assortment

Heredity, Gene Regulation, and Development Mutation A. Overview.

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