IB BIO D1.3

Mutations and gene editing

Gene mutations

  • A mutation is a change in the DNA sequence. Mutations are rare and usually happen during DNA replication

  • There are 3 types of mutations: substitutions, insertions, and deletions.

Mutations

Base substitutions

  • A base substitution is when a single nucleotide is changed in the sequence. This is referred to as a single-nucleotide polymorphism (SNP)

  • Base substitutions can represent different versions of genes and can be the cause of disease and cancers.

  • Because of the degeneracy of the genetic code, some of the single base substitutions may not affect the gene functioning.

Insertions and deletions

  • When an extra nucleotide is inserted or deleted from the sequence it causes a frameshift mutation. This causes the protein to not function.

  • Frameshift - the insertion or deletion of multiples of three

  • HTT gene - an insertion of multiple copies of CAG to chromosome 4 causes Huntington’s disease.

  • Delta 32 mutation of the CCR5 gene - a deletion of 32 nucleotides has been removed, causing the CCR5 receptor to malfunction. This mutation prevents the HIV from attacking the cells.

Mutagens and replication errors

  • Mutations in DNA can be caused by viruses, mutagens, ionizing radiation, or a random error in DNA replication (rare)

  • Mutagens are chemicals that can cause a genetic mutation. they can be from inside the body or from the environment.

  • Examples: certain enzymes (inside) or benzene, found in products like nail polish remover (outside)

Locations of mutations

  • Mutations can occur anywhere in the base sequence, but some bases have a higher probability of mutation than others.

  • Satellite DNA, non-coding DNA found in the centromere, has a higher mutation rate than coding DNA.

  • CpG sites, where cytosine is followed by guanine. Cytosine can mutate into thymine.

  • No natural mechanism is known for making deliberate changes to the DNA

Mutations Good or Bad?

Mutations in germ cells and somatic

  • Not all mutations pass on to the next generation

  • Mutations found in germ cells, sex cells, can be passed on to the offspring

  • Mutations found in somatic cells and body cells will not be passed on. These mutations are associated with cancer.

Genetic Variation

  • Mutations can be good bad, or neutral

  • The environment in which the organism lives determines this

  • Mutations are what drives natural selection

Genetic editing

Gene Knockout

  • Once scientists mapped the human genome, they then needed to determine what the genes did

  • One way to figure out what something does is to remove it and see what happens, This is called gene knockout

  • A library of organisms with knockout genes allows researchers to study the effects of pharmaceuticals for human use. For example: mice are used to study obesity, diabetes, and anxiety.

CRISPR-Cas9 gene editing

  • CRISPR-Cas9 is a gene-editing technology

  • With this technology. DNA can be cut so that sections can be deleted or added

  • This editing process works in all organisms because DNA is universal

Possible benefits of CRISPR-Cas9?

  • This technology can be used to delete genes that cause disorders like Huntington’s disease or entire chromosomes in an embryo that has Down Syndrome.

  • It can also be used in plants to yield more fruit or increase their nutrients

  • There are ethical considerations, when altering a gene there could be off-target effects

Conserved and highly conserved sequences

  • There are sequences of DNA that are very similar between species that are related.

  • Conserved Sequences are identical or similar across a species or group of species

  • Highly conserved sequences are identical sequences over long periods of evolution. (low rate of mutation)

Reasons for conserved sequences

  1. Products made by the gene are needed in multiple species. For example, DNA replication

  2. A slower rate of mutation in those genes.

Cell and Nuclear Division

Generating New Cells

  • Mitosis cells must divide and make copies for growth and repair

  • Meiosis cells divide and make gametes with half the number of chromosomes

  • A parent cell or mother cell will divide to make new cells

  • Prokaryotic cells reproduce asexually. They only have s single chromosome and divide by binary fission to make copies of the original

Cytokinesis

  • Cytokinesis is the moment when the 2 cells being made by cell division split into separate cells. This process is different depending on if it’s an animal or plant cell.

  • In animal cells, a cleavage furrow forms when actin and myosin proteins pinch the cell membrane together

  • In plant cells, a cell plate forms when vesicles assemble sections of membrane and cell wall

Cell Division

Equal and Unequal Cytokinesis

  • Most of the time, when a cell divides, the 2 daughter cells are equal. Each should contain DNA, Mitochondrion, and other organelles needed by that type of cell.

  • Sometimes the daughter cells are not identical with an unequal distribution of the parent cell’s resources.

  • Example;

    • Oodenesis - 4 cells are produced but only 1 contains most of the cytoplasm and organelles needed for the zygote. The other 3 cannot be used and are instead supportive cells for the 1.

    • Yeast cells - cells divide using a process called budding, when the daughter cell becomes big enough, it will pinch off and become a separate cell.

Nuclear Division

  • Division of the nucleus must occur before cells divide to ensure both new cells have their nucleus

  • Mitosis results in 2 new daughter cells that are exactly like the original cell ( same # of chromosomes)

  • Meiosis results in 4 daughter cells that have half the number of chromosomes that are genetically different from each other. This process produces gametes for sexual reproduction.

DNA Replication before cell division

  • The cell cycle is made up of 2 stages, Interphase and Mitotic phase

  • Interphase is divided into 3 parts, D1, S, D2

  • The S phase of interphase is when DNA must replicate for cell division

  • When DNA replicates, there are now 2 copies of DNA held together by a centromere

DNA Condensation

  • Now that the DNA has been replicated, cell division can start

  • DNA needs to be supercoiled to move correctly during cell division

  • This process of condensation involves the DNA being wrapped around histone proteins

  • During cell division, the centrosome will produce, microtubule spindle fibers that are needed to guide the chromosomes to the correct position, Motor proteins push and pull objects along the microtubules like a track

Mitosis

  • is divided into 4 phases: Prophase, Metaphase, Anaphase, and Telophase (PMAT)

  • Prophase

    • Chromatin coil

    • nuclear envelope disappears

    • Mitotic spindle forms

    • centrosomes move towards opposite poles

    • Chromosomes are referred to as

      • Sister chromatids

  • Metaphase

    • The sister chromatids move to the middle or equator of the cell

  • Anaphase

    • Sister Chromatids separate and move to opposite poles

    • Now they are referred to as chromosomes

  • Telophase

    • The opposite of prophase

    • Nuclear envelope forms

    • Chromosomes start to elongate

    • spindle fiber disappear

    • cell goes through cytokinesis

Meiosis

Reduction Division

  • Meiosis is a reduction division because the 4 daughter cells that are produced have half the number of chromosomes as the parent cell

  • The parent cell is said to be diploid (2n) meaning they have the total number of chromosomes for the species

  • The daughter cells produced from meiosis are said to be haploid meaning they have half the number of chromosomes for the species

  • Example

    • Humans

    • 2n-46

    • n-21

    • Meiosis happens in 2 rounds, Meiosis I and Meiosis II

  • Meiosis I

    • During meiosis I, the chromosomes are reduced by half

  • Prophase I

      • chromosomes become visible

      • Homologous chromosomes pair up (1 from mom and 1 from dad, together they are called bivalent)

      • Crossing-over occurs

      • Meiotic spindles form and chromosomes go to the opposite poles.

      • Nuclear envelope disappears

  • Metaphase I

    • Homologous pairs line up down the center

    Anaphase I

    • Homologous pairs separate and move to opposite poles

  • Telophase I

    • Mitotic spindle disappears

    • nuclear envelope reappears and chromosomes uncoil

    • Cytokinesis takes place

  • Meiosis II

    • During the second round of segregation, the sister chromatids are separated

  • Prophase II

    • DNA condenses

    • meiotic spindles form

    • Centrosomes separate to opposite poles

    • (NO crossing-over occurs)

  • Metaphase II

    • Sister chromosomes line IP down the center

  • Anaphase II

    • Sister chromosomes separate and go to opposite sides

  • Telophase II

    • Chromosomes uncoil

    • nuclear envelope reappears

    • Meiotic spindles disappear

    • Cytokinesis takes place

    • We now have 4 genetically different haploid cells