Genetics Bio
Cell division
creating two cells from one, goal is to pass down genetic information as well as organelles to the next generation, Parent/mother cell: the cell that produces the copy,
Daughter cells: the cells produced from the parent cell
Cell division: Prokaryotes
Uses the process of binary fission, they copy their dna semi-conservatively, 2 DNA loops attach to the membrane, membrane elongates, creates a septum and pinches off (cytokinesis), this forms two odaughter cells
Semi-conservatively meaning (binary fission)
Dna (double stranded), splits in half, each half gets new nucleotides added to it
Cell division: Eukaryotes
Mitosis: cell division that produces 2 genetically identical daughter cells to the parent cells
Meiosis: a type of cell division sexually reproducing organisms that produces sex cells (sperm and egg)
Why do cells divide
Growth: multicellular organisms increase their size by increasing their number of cells through mitosis, otherwas SA:volume ration would be too low
Asexual reproduction: certain eukaryotic organisms may reproduce asexually by mitosis
tissue repair: damaged, infected, or dead cells need replacing
Embryonic development: a fertilized egg (zygote) will undergo mitosis and differentiation in order to develop into an embryo
DNA replication as a prerequisite for mitosis & meiosis
Each chromosome has a partner - one from each parent, both copies are required for the cell to function.
Steps:
normal somatic (body cell) two sets of chromosomes from each parent (diploid = 2n)
Just before prophase, the cell has copies of every chromosome (sister chromatids, temporarily 4n)
Following mitosis, each new nucleus is diploid (2n), with a complete set of chromosomes
Interphase
spends about 80% of its time in itm very active phase of the cell cycle (a functioning cell basically)
G0 is the resting phase (no dividing),
g1 characterised by rapid growth and metabolic activity (protein synthesis),
S: DNA synthesis and replication,
G2: centrioles replicate (preperation for cell division, DNA coils into chromosomes, chloroplasts and mitochondria replicate
sister chromatids - definition
are duplicated chromosomes attached by a centromere. After anaphase when the sister chromatids separate they should then be referred to as chromosomes
Centromere - definition
the part of a chromosome that links sister chromatids
Kinetochore - definition
a protein structure attached to the centromere where astral microtubules attach to
astral spindle microtubles - definition
also referred to as spindle fibres
centrioles - definition
organize spindle microtubules. In animal cells two centrioles are held by a protein mass referred to as a centrosome
chromatin - definition
the uncoiled form of dna
Supercoiling of chromosomes
during the g2 phase, chromatin begins to condense (called supercoiling), when they condense after duplication it does so by winding around specific proteins called histones like thread on a spool. Each one is called a nucleosome, multiple of them coil into cylindrical fiber is called solenoid, which then supercoils intoa visible structure (chromatin)
reasons for supercoiling
they wouldn't be able to fit in the nucleus without supercoiling, chromosomes need to be stored compactly to fit within the nuclei of cells, the problem becomes more acute during mitosis when chromosomes need to be short and compact enough that they can be separated and moved to each end of the cell
Prophase
the centrosomes move to opposite poles, motor proteins move along overlapping astral spindle fibers causing them to move opposite sides. Astral spindle fibers attach to the kinetochore. Dna supercoils, the nuclear membrane breaks down and disappears
Metaphase
Spindle microtubules attach to each chromatid at the centromere, contraction of the microtubule spindle fibres cause the sister chromatids to line up along the centre of the cell (metaphase plate), centrosomes are now opposite poles
Anaphase
motor proteins push microtubules in opposing directions causing the centromere to split and sister chromatids to move to opposite sides. These chromatids (now chromosomes) move towards opposite poles (ends) of the cell at the end of phase, each pole of the cell has a complete, identical set of chromosomes
Telophase
chromosomes are at each pole, spindle apparatus disappear and the nuclear membrane reappears around each set of chromosomes. Nucleoli reappear, chromosomes uncoil to chromatin, cell is elongated and ready for cytokinesis
Cytokenisis - Animal cells
a ring of contractile protein immediately inside the plasma membrane at the equator pills the plasma membrane inward. The inward pull on the plasma membrane produces the characteristic cleavage furrow. When the cleavage furrow reaches the centre of the cells it is pinched apart to form two daughter cells.
Cytokinesis - Plant cells
during telophase, membrane-enclosed vesicles derived from the golgi apparatus migrate to the centre of the cell. Vesicles fuse to form tubular structures. The tubular structures merge (along with more vesicles) to form two layers of plasma membrane. The cell plate continues to develop until it connects with the existing cell's plasma membrane. This completes the division of the cytoplasm (formation of two daughter cells). Vesicles deposit by exocytosis, pectin, and other substances in the lumen between the daughter cells to form the middle lamella, both daughter cells secrete cellulose to form their new adjoining cells.
Cyclins and the control of the cell cycle
cyclins were discovered by Timothy Hunt in 1982 while he was conducting research into the control of protein synthesis in sea urchin eggs. Cyclin was a protein that went through repeated increases and decreases in the concentration that coincided with the phases of the cell cycle. The contribute ot the control of the cell cycle, and genes were responsible for starting the cell cycle
Cyclins
a family of proteins that control the progression of cells through the cell cycle. Cells cannot go to the next stage unless the specific cyclin reaches its threshold, this ensures cells only divide when needed. Cyclins bind to enzymes called cyclin-dependent kinases, which then become active and attach phosphate groups to other proteins in the cell. This attachment triggers other proteins to become active and carry out tasks
Cyclin expression
cyclin concentrations need to be tightly regulated to ensure the right sequence. Different cyclins bind to and activate different classes of CDK, cyclin levels peak when their target protein is required for function
G1 cyclin
tells the cell to replicate the DNA
Mitotic cyclin
binds to CDK to form a mitosis promoting factor, which triggers chromosome condensation, fragmentation of the nuclear membrane, and spindle formation, levels peak in metaphase and by anaphase this type of cyclin is destructed
G0 phase cyclin
not all cells are continually replicating. Some cells may enter into a non-dividing g0 phase, they are either dormant, aging, or deteriorating. Quiescent cells may re-enter g1 phase at a later time (dormant), cells will only divide a finite time before reaching senescence (dying cell), specialised cells permanently enter g0 (e.g neurons)
Tumour formation and cancer
Tumours are an abnormal growth of tussue, can be benign (non-cancerous) or malignant (canceerous, they move throughout the blood stream and other streams and spread throughout the body through metastasis)
Mutagens
agents that cause gene mutations. Not all mutations result in cancers, but anything that does has the potential to cause cancer: chemicals that cause mutations (carcinogens), high energy radiation, short-wave ultraviolet light, some viruses
Oncogene
if a mutation occurs in a proto-oncogene (gene that controls the cell cycle) it will become an oncogene, which overproduces protein that will cause uncontrolled cell division
RAS gene
genes that code for a G protein (membrane protein). Normally a growth factor binds to a cell surface receptor, the G protein will then trigger a cascade of protein kinases which lead to normal cell division. If mutated, the G protein can trigger kinase cascade without the growth factor present, leading to uncontrolled cell division
Tumour-suppressor genes
they encode for proteins that inhibit cell division or promote apoptosis. Mutations in these genes can cause proteins to be deactivated or non-functional, resulting in a cell that does not undergo apoptosis if mutated. P53 gene codes for a p53 protein (transcription factor, promotes formations of other proteins), if mutated it will not produce p53 and cells that are meant to die will continue to divide.
Factors (not mutagens) for tumours
the vast number of cells in the body (more cells, higher chance for mutation), the longer a life span, strong positive correlation between smoking and lung cancer
Mitotic index
the ratio between the number of cells in mitosis in a tissue and the total number of observed cells. Obtain a prepared slide and find area of cell division, create a tally chart, look at approx. 100 cells in this region and classify each cell as mitosis or interphase. Do mitosis cells/total cells
Chemotherapy
can have effects system-wide beyond the primary tumour, given through an intervenous injection or orally, drugs can impact healthy tissues as they are non-specific to cancer cells (just cells that divide quickly) side effects include hair loss, mouth sores, nausea and fatigue
radiation
high energy invisible light waves damage cancer cells, causes tumours to shrink, can kill cancer cells for weeks to months after initial treatment, can be given through injection into the tumour or through a beam outside the body, side effects include nausea, mouth sores, throat problems, and fatigue
Sexual reproduction
involves the joining of two gametes (sperm and egg), the process of combining is called fertilization, the cell that results from this is a Zygote. Gametes are haploid (they contain half the number of chromosomes as the parent cell) the zygote cell is diploid, which makes up 46 chromosomes
Meiosis
a reduction division of the nucleus to form haploid gametes.
Genetric reduction
meiosis produces haploid daughter cells with half the number of chromosomes of the diploid parent cell
Genetic recombination
gametes have different combinations of alleles; offspring are genetically different from each other and their parents; this increases genetic variation.
Rounds of cell division (meiosis)
Meiosis 1 separates the homologous pairs of chromosomes (2n --> n or reduction division)
Meiosis 2 separates the sister chromatids
alleles
the different versions of each gene
Interphase (meiosis)
In the S-phase of the interphase before meiosis begins, DNA replication takes places. Chromosomes are replicated and these copies are attached to each other at the centromere. The attached chromosome and its copy are known as sister chromatids. Following S-phase, further growth and preparation take place for meiosis.
Prophase I (meiosis)
the homologous chromosomes associate with each other to form bivalents or tetrad (4 chromatids) in a process called synapsis. DNA supercoils and chromosomes condense, the nuclear membrane dissolves, centrioles migrate to the poles of the cell. Crossing over between non-sister chromatids take place. This results in recombination of alleles and is a source of genetic variation in gametes.
crossing over (meiosis)
The DNA molecules of two non-sister chromatids (one maternal and one paternal) break at the same place. The two broken chromatids join together, the two homologous segments trade places creating hybrid chromosomes with new combinations of maternal and paternal genes. The hybrid chromosomes are referred to as recombinant chromosomes since they have gene combinations different from those carried by the original chromosomes. The point of crossing over is called the chiasma, this occurs between sister chromatids and should appear in the central space.
Metaphase I (meiosis)
the bivalents line up at the equator. Random orientation occurs, each bivalent aligns independently and hence the daughter nuclei get a different mix of chromosomes. This is a significant source of genetic variation: there are 2^n possible orientations in metaphase I and II. That is 23^23 different combinations of gametes in humans. Alleles have a 50 percent chance of moving to a particular pole. The direction in which one bivalent aligns does not affect the alignment of other bivalents. Therefore different allele combinations should always be equally possible (if the gene loci are on different chromosomes - this does not hold for linked genes)
Telophase I (meiosis)
the nuclei are now haploid (N) not diploid: they each contain one pair of sister chromatids for each of the species chromosomes. The cytoplasm begins to divide by ctyokinesis. New nuclei form. Chromosomes decondense.
Anaphase I (meiosis)
homologous pairs are separated and pulled to opposing poles. Spindle fibres contract, this is the reduction division - the bivalent is split and half the chromosomes move towards each pole
Prophase II (meiosis)
nuclear membranes dissolves, chromosomes, consisting of two sister chromatids, condense, no crossing over, centrioles move to opposite poles
Metaphase II (meiosis)
pairs of sister chromatids align at the equator. Spindle fibres form and attach at the centromeres. Random orientation again contributes to variation in the gametes, though not as much of an extent. This is because there is only a difference between chromatids where crossing over has taken place
Anaphase II (meiosis)
the sister chromatids are separated. The chromatids (now called chromosomes) are pulled to opposing poles. Spindle fibres contract, centromeres split
Telophase II (meiosis)
four new haploid nuclei are formed, nuclear membrane reforms, chromosomes condense, cytokinesis begins, dividing the cells, results in four haploid gamete cells, fertilization of them is a diploid zygote
Gene Mutation
a change to the base sequence of a gene. This can occur spontaneously, as a result of errors in DNA replication or they can be caused by mutagens. Most mutations are either neutral or harmful
Substitution
type of gene mutation, one base in the coding sequence of a gene is replaced by a different base (e.g mispairing of G to T)
Insertion
Type of gene mutation, a nucleotide is inserted, so there is an extra base in the sequence of the gene. This is a more major change as it requires a break to be made in the sugar-phosphate backbone of the DNA molecule
Deletion
type of gene mutation, a nucleotide is removed, so there is one base less in the sequence of the gene. This requires two breaks in the sugar-phosphate backbone
Point mutation
only one nucleotide is involved
Mutations in general
sometimes two or more bases can be involved in a mutation, or even thousands of bases when a segment of a chromosome is involed. Mutations that occur in gametes can be passed on to offspring and cause genetic disease.
Base substitution
the most significant type of mutation where one base is replaced by another base. This can result in the change of a single amino acid in the polypeptide
Silent/same-sense mutation
the change in base sequences has no effect on the amino acid produced, because the redundancy of the genetic code
mis-sense mutation
the change in base sequence has caused one different amino acid to be produced (e.g sickle cell anemia). This kind of mutation may not have much effect if the new amino acid has a similar structure and chemical properties
Nonsense mutation
the change in base sequence has caused a STOP codon to be produced, so the polypeptide produced is shortened/premature (e.g cystic fibrosis)
Consequences of base substitutions
inn non-coding DNA between genes on chromosomes, base substitutions are unlikely to have any effect (only changes to the coding sequences of genes can affect the amino acid sequences of polypeptides). Same-sense mutations do not affect the polypeptide but can make it possible for a second mutation to change it. Nonsense and mis-sense alter amino acids sequence and can cause lethal effects.
Single-nucleotide polymorphisms
the DNA from individual humans is sequences, large numbers of base substitutions are found that have happened at some time in the past, they occur in noncoding regions of DNA, some of them are associated with certain diseases, scientists can use this to determine an individual's genetic predisposition to develop a disease (can also help with heritage)
Insertions and deletions reading
major insertions or deletions of nucleotides in a gene almost always result in the codon for polypeptide to stop functioning. Minor ones can also result in total loss of functions of a polypeptide, because they are frameshift mutations, they change the reading frame for every codon
BRCA1 - insertion and deletion
gene codes for the BRCA1 protein in humans, it is a tumour supressor and repairs DNA. If this gene mutates the protein cannot carry out its function, the consequences is an increased risk of tumour formation and cancer (particularly breast, ovarian and prostate). Over 20,000 variants of these have been identified, some are benign and some aren't
HTT gene - insertion and deletion
huntington's disease is a genetic condition that causes severley debilitating nerve damage but does not show symptoms until 40 years of age. People who have the gene can pass it on to their offspring without knowing. Caused when a gene found on chromosome 4 has an insertion mutation where multiple copies of CAG are added to the gene, this has an adverse effect on the brain cells, if a person has more than 40 repeats of trinucleotide, they will be affected.
CCR5 - Deletions
leukocytes (white blood cells) move towards zones of infection in order to protect the body from invaders. Chemokines are chemical signals that tell them where to go. HIV-1 uses these receptors as an entry point to infect leukocytes called CD4 cells
HIV
those who have a working set of CCR5 genes on chromosome 3 are at risk of the virus entering their cells if they are exposed to HIV-1. At the stage where white blood cells are gone (no immune system) it is called AIDS. Delta 32 mutation is a mutation of the CCR5 receptor gene, since 32 is not a multiple of 3 this mutation causes a frameshift and a stop codon to form where it should not be. The ribosome will stop making the protein and will not produce the cytokine receptor that HIV needs to infect.
Mendel's law of independent assortment
The presence of an allele of one of the genes in a gamete has no influence over which allele of another gene is present.
This only holds true for unlinked genes (genes on different chromosomes)
Random orientation
The presence of an allele of one of the genes in a gamete has no influence over which allele of another gene is present
random orientation vs independent assortment
Random orientation refers to the behaviour of homologous pairs of chromosomes (metaphase I) or pairs of sister chromatids (metaphase II) in meiosis.
Independent assortment refers to the behaviour of alleles of unlinked genes as a result of gamete production (meiosis).
Due to random orientation of the chromosomes in metaphase I, the alleles of these unlinked genes have become independently assorted into the gametes
spermatogenesis
The formation of sperm gametes, follows meiosis perfectly, continues until death, 1 spermatogonium creates 4 haploid cells
oogenesis
Formation of egg gametes.
Notice how there is unequal division of the cytoplasm.
This creates something called a polar body which will eventually degenerate.
The functioning cell will go through meiosis II and another polar body is formed
1 oogonium creates 1 haploid cell