Before midterm Flashcards
DNA
Deoxyribonucleic acid; information-carrying genetic material that compromises the genes
RNA
Ribonucleic acid; information-carrying material derived from DNA by transcription
Polymers
Subunits bonded together
Nucleotide
Polymer of DNA and RNA compromised of:
Phosphate group
5-C sugar
Cyclic N-containing base
Adenine
Purine base found in RNA and DNA
Thymine
Pyrimidine base found in DNA
Cytosine
Pyrimidine base found in DNA and RNA
Guanine
Purine base found in DNA and RNA
Uracil
Pyrimidine base found in RNA in place of thymine
Pairs with thymine
Adenine
Pairs with cytosine
Guanine
Purine
Double-ring bases
i.e. Adenine and Guanine
Pyrimidine
Single-ring bases
i.e. Cytosine and thymine
Phosphodiester bonds
Connect nucleotides
Characteristics of DNA structure
Double-helix
Two strands held together by hydrogen bonds between complementary bases
Strands run antiparallel
Two strands have opposite chemical polarity
Makes DNA uniquely suited to store and transmit genetic information
Complementarity of strands
Two strands have opposite chemical polarity
One runs 5’ to 3’ so at the 5’ end there is a free phosphate group and at the other a free hydroxyl group
The other strand runs 3’ to 5’
Most common form of DNA
B-DNA (conformation that DNA takes under physiological conditions (aqueous protoplasms)
Important for protein binding
Major and minor grooves
Major and minor grooves
Two grooves of a DNA double helix are not identical
Chromatin
Complex of DNA and proteins in eukaryotic chromosomes
Chromosome
Darkly staining nucleoprotein bodies that are observed in cells during division. Each chromosome carries a linear array of genes
How do we go from DNA to chromosome?
Chromosomes contain a single giant molecule of DNA extending from one end to the other but is highly condensed (needs to be in order to get 3 billion genes into one tiny cell)
Chromosomes are composed of
DNA, RNA, proteins
First level of condensation
Packaging DNA as negative supercoil into nucleosomes (2nm –> 11nm)
Produces an 11 nm fibre
First level of condensation (negative surer coil)
Nucleosome
Nuclease-resistant subunit of chromatin that consists of about 146 nucleotides of DNA wrapped around 8 histone proteins
Nucleosome core
8 histone protein core (octamer) chills while being wrapped in DNA
Linker region
Space connecting nucleosome balls
Bunch of DNA that varies in length from 8 to 114 nucleotide pairs
Endonuclease
Enzymes inside nucleus
Second level of condensation
Additional folding or supercoiling of 11 nm nucleosome fibre to produce a 30 nm chromatin fibre
Driven by nucleosomal interactions and histone H1 very improtant
30 nm fibre
The basic structural unit of the metaphase chromosome (DNA in its most condensed form
Histones
Group of proteins rich in basic amino acids that function in the coiling of DNA in chromosomes and in the regulation of gene activity
H1
After DNA wraps around nucleosome core, 9th guy (histone) comes in and anchors to seal the deal forming a complete nucleosome
Complete nucleosome
DNA wrapped around 8 histone protein core and then anchored by 9th histone called Histone H1
Third level of condensation
Attachment of the 30 nm fibre at many positions to a non-histone protein scaffold
Cohesins
Proteins that hold sister chromatids together at centromere
Condensins
Proteins that function to condense 30 nm DNA fiber of chromatin within one sister chromatid
Non-histone units
Cohesin and condensins
Centromere
Provide the point of attachment of chromosomes to microtubules in the mitotic spindle
Important for meiotic and mitotic processes
Centromeres
Mitotic spindle
Macromolecular machine that segregates chromosomes to two daughter cells during mitosis
Telomeres
These guys chill on the ends of chromosome to protect them from being eaten by enzymes and to prevent them for merging together with other chromosome ends and facilitate replication of the ends of the linear DNA
Mitosis
Disjunction of duplicated chromosomes and division of the cytoplasm to produce two genetically identical daughter cells
Diploid
An organism or cell with two sets of chromosomes (2n) or two genomes
Haploid
An organism or cell having only one complete set of chromosomes (n) or one genome
Two diploid cells
Final product of mitosis of diploid cell
Four haploid cells
Final product of meiosis of diploid cell
Chromatid
One of the two identical strands resulting from self-duplication of a chromosome in mitosis or meiosis
Identical sister chromatids
Each mitotic chromosome is comprised of a pair of sister chromatids (so real name of chromosomes)
Daughter cell
Product of cell division
Disjunction
Separation of homologous chromosomes during anaphase of mitotic or meiotic divisions
In mitosis ________ __________ and ___________ ________ are divided more or less equally between daughter cells
Cellular organelles, cytoplasmic contents
In mitosis __ and _____ _______ are fragmented at the time of division and reformed in the daughter cells
E.R., Golgi complex
___________ and ____________ are randomly divided between daughter cells
Mitochondria, chloroplasts
_______ ___________ must be duplicated exactly and distributed equally and exactly to daughter cells
Nuclear chromosomes
Cell Cycle
Set of stages of cell division
Main stages of cell cycle
G1 S G2 M Interphase
G1 phase
Gap 1: Growth, cellular metabolism
S phase
Synthesis: DNA replication (chromosome duplication)
G2 phase
Gap 2: Preparation for mitosis
M phase
Mitosis: Chromosomal separation and cytokinesis
Interphase
The time between successive mitoses
Cells that are not actively cycling
Enter a state called G0 from G1 and are said to be quiescent
Preparation for mitosis
Making proteins like cohesins and condensins
When mitosis begins
Each chromosome has been duplicated
“c”
DNA content
DNA content in haploid cell
“c”
DNA content in diploid cell
“2c”
Number of unique genes
“n”
Weight of DNA
“c”
Somatic cell
A cell that is a component of the body, in contrast with a germ cell that is capable, when fertilized, of reproducing the organism
Diploid somatic cell
“2n, 2c”
Diploid somatic cell after DNA replication
“2n, 4c”
IPMAT
Cycle of mitosis: Interphase Prophase Metaphase Anaphase Telophase
Interphase
Chromosmes duplicate to produce sister chromatids
Homologous chromosomes
Chromosomes that occur in pairs and are generally similar in size and shape, one having come from the male parent and one from the female parent
Chromosomes containing the same array of genes
Homologous chromosomes
Prophase
Duplicated chromosomes condense, holding on through cohesin and condensin
Metaphase
Duplicated chromosomes migrate to the equatorial plane (midway between spindle poles) of the cell and the nuclear membrane breaks down
Anaphase
Cohesion breaks down and sister chromatids of each duplicated chromosome move to opposite poles of the cell, spindle poles moving further apart
Telophase
Chromosomes cluster at opposite spindle poles and become dispersed and decondense (condensin is degraded) finally a nuclear envelope assembles around chromosomes
Cytokinesis
During telophase daughter cells form and are “2n, 2c” once again
Microtubule organizing center (MTOCs)
Region in eukaryotic cell that generates microtubules used during cell division
Always exist but only organize during mitosis
Short arm
“p”
Long arm
“q”
Occurs in bodies stem cells
Mitosis
Occurs in germ (sex) cells
Meiosis
A cell that is about to divide
Parent cell
Daughter cells
Products of division
When meiosis begins
Duplicated gene
23 pairs of chromosomes
Somatic human cells
Different pairs of chromosomes
Carry different sets of genes
Homologues
Carry the same set of genes
Heterologues
Chromosomes from different pairs
Involves two cell divisions
Meiosis
Meiosis I
Homologous chromosomes separate
Meisosis II
Sister chromatids separate
Major difference in meiosis and mitosis
Prophase to metaphase
Prophase I
- Leptonema
- Zygonema
- Pachynema
- Diplonema
- Diakensis
Leptonema
Chromosomes each consisting of two sister chromatids begin to condense
Zygonema
Homologous chromosomen begin to pair
Pachynema
Homologous chromosomes are fully paired, crossing over happens
Diplonema
Homologous chromosomes separate except at chiasmata
Crossing over
Breakage of chromatids and exchange of broken pieces between homologous chromosomes (non-sister chromatids)
Chiasmata
Following crossing over homologous chromosomes start to pull apart but remained joined at cross-over junctions
Synapsis
Pairing of homologous chromosomes
Reduction division
Cell division in meiosis I
Non-disjunction
Failure of two homologous chromosomes to pass to separate cells
Down-syndrome
Chromosome non-disjunction
Meiosis I produces
Two haploid daughter cells that are genetically distinct
Diakensis
Paired chromosomes condense further and become attached to spindle fibers
Metaphase I
Paired chromosomes align at the equatorial plane in the cell
Anaphase I
Homologous chromosomes disjoin and move to opposite poles of the cell
Telophase I
Chromosome movement is completed and new nuclei begin to form
Meiosis II
Resembles a mitotic division except the products are haploid
Spermatogenesis
The process by which maturation of the gametes of male takes place. All four develop into sperm
Oogenesis
The formation of the egg or ovum in animals. Usually only one of the four haploid cells becomes an egg the other three degenerate
Locus
Specific region on a chromosome (could be a gene or any unique sequence)
Allele
Alternate form of a gene (A or a)
Upper case letter
Dominant allele
Dominant allele
Expressed factor
Recessive allele
Latent factor
Lower case letter
Recessive allele
Alleles are typically designated after the
Recessive trait
Genotype
Allelic combination
Phenotype
Physical appearance
Wild type
The customary phenotype or standard for comparison
Gametogenesis
Formation of gametes beginning when undifferentiated diploid cells undergo meiosis to produce haploid cells. The haploid cells then differentiate into mature gametes “n, c”
Spermatogonia, oogonia
Undifferentiated diploid cells “2n, 2c”
Primary o/spermat-ocyte
Before completion of first meiotic division “2n. 4c”
Secondary o/spermat-ocyte
After completion of first meiotic division “n, 2c”
Gametes
Mature male or female reproductive cell
Inbreeding
Matings between related individuals
Inbreeding leads to
High probability of recessive mutations popping up
Designed to study one trait at a time
Mendel’s experiments
Homozygous
Both alleles are identical (ll or aa or BB)
Heterozygous
Two alleles are different (Ll or aA or Bb)
P0
Parental generation in a genetic cross
F1
Offspring generation in a genetic cross
F2
Grand-offspring generation in a genetic cross
Monohybrid cross
A cross between parents in which only one trait is being considered
Mendel’s heritable factor
Gene
Principle of dominance
In a heterozygote one allele may conceal the presence of another
Principle of segregation
In a heterozygote two different alleles (l and L) segregate from each other during the formation of gametes
Hybrid
An offspring of a cross between unrelated strains (homo parents different in one or more genes)
Principle of independent assortment
Alleles on different pairs of chromosomes assort independently from one another, occurring during anaphase 1 of the meiotic cycle
Monohybrid cross ratio
3:1
Dihybrid cross ratio
9:3:3:1
Produces one kind of gamete
Homozygous parent
Equation for possible haploid gametes?
Alleles^genes
Punnet square method
Possible gametes go across top and side then fill in square
Forked-line method
Look at each gene independent of one another
Probability method
Find probability of each independent event occurring
Multiplicative rule
Probability of independent events occurring together is the product of their individual probabilities of occurrence (and = X)
Additive rule
Probability of at least one event happening is the sum of their individual probabilities (or = +)
Test cross
Performed to determine individual’s genotype. Individual of unknown genotype must be crossed with a homozygous recessive individual
Pedigrees
Diagrams that show the relationships among the members of a family
Trait is likely showing a recessive mode of inheritance
If…
the trait suddenly appears in a pedigree
the trait “skips” a generation
Assume that unrelated individuals marrying into the family…
Do not carry the recessive allele
A trait is likely showing a dominant mode of inheritance
If…
every individual has at least one affected parent
the trait is manifested in at least one individual in every generation once the trait appears
Binomial probability
For a total number of "n" progeny we can calculate that exactly "x" number will fall into one class and "y" number will fall into another (n!/x!y!)p^xq^y
The absence of a phenotype
Doesn’t necessarily reflect the absence of a causative genotype
Huntington’s disease
Neurodegenerative disorder in humans caused by an autosomal dominant mutation and one of the first genetic diseases mapped on pedigree scheme
Autosomal chromosomes
Not a sex chromosome (22)
XX
Females
XY
Male
Pseudoautosomal genes
Genes present on both the X and Y chromosomes but mostly in the terminal regions. They do no follow X or Y-linked patterns of inheritance
Hemizygous
Only one copy of chromosome
Gene on X chromosome doesn’t have homolog on Y chromosome
X-linked mutation
In a hemizygous state (XY) if one gene is mutated and is recessive the recessive allele would manifest itself. In a heterozygous state the recessive allele would be suppressed by dominant wild type allele (XX)
X-linked recessive disorder
Hemophilia or colorblindness
More common in males than in females
Disorders which are caused by recessive X-linked mutations
Y chromsome
Carries fewer genes than the X chromosome
X-inactivation
Dosage compensation of X-linked genes (i.e. not fair that there are twice as many genes on the X chromosome in females than in males so in mammals one of the female X-chromosomes are inactivated)
Barr body
A condensed mass of chromatin found in the nuclei of placental mammals that contains one or more X chromosomes (altered state of inactive X-chromosome)
Dosage compensation in Drosophila
Achieved by hyper activating the single X chromosome in males
Dosage compensation in cats and mice
Results in a mosaic coat colour because the gene for coat colour resides on the X-chromsome
Mutation
A change in the DNA at a particular locus in an organism
Spontaneous mutations
A result of an error during DNA synthesis:
- Incorporation of rare isoforms of the four bases that have altered base pairing properties
- The inherent fallibility of replication proteins
Tautomers
Two existing isoforms of the nitrogenous bases of DNA
Incorporation of a rare isoform during DNA replication
Can lead to a change in DNA sequence
Rare isoforms
Have altered base pairing properties
Inherited mutations
Mutations of DNA in the germ line (during mitotic divisions of spermatogonia or oogonia)
Palindromes
A segment of DNA in which the base-pair sequence reads the same in both directions from a central point of symmetry
Hot spots for spontaneous mutations during DNA synthesis
Simple repeats
Symmetrical repeats
Palindromes
Induced mutations
Exposure to chemical mutagens
Exposure to radiation (UV light)
DNA transposable elements
Thymine dimer
Pyrimidines adsorb UV energy resulting in dimerization. This creates a hiccup for DNA polymerase and it causes changes in DNA sequence
Point mutation
Changes that occur at specific sites in genes (involving a change of only one nucleotide base)
Three types of point mutations
- Silent
- Nonsense
- Missense
Silent mutation
When the one nucleotide base that is changed creates a codon synonymous to the original codon then the mutation has no effect
Nonsense mutation
When the one nucleotide base alters the codon so that it creates a premature stop codon
Missense mutation
When the one nucleotide base alters a codon so that it no longer makes sense (specifying a different amino acid than the original codon)
Frameshift mutations
A mutation that changes the reading frame of an mRNA (either by inserting or deleting nucleotides)
Types of frameshift mutation
- Insertion
2. Deletion
Insertion mutation
When a series of extra base pairs is inserted into DNA
Deletion mutation
When a series of DNA base pairs are deleted or lost
Mutations that affect the coding region
- Change protein to a non-functional form
- premature truncation
- changes to protein folding - Changes in post-translational modification
- prevent proper localization of the protein
- “unactivatable”
Changes to protein folding
- Prevent proper localization of the protein
- Targeted for degredation
- Compromised activity
Mutations that affect non-coding regions
- Prevent or reduce transcription
- Prevent or reduce translation
- mRNA is unstbale
- ribosomes can’t bind
- mutation of the start codon
____________ _________ are mutations that occur without a known cause
Spontaneous mutations
Polymorphism
Ant allele found at appreciable frequencies (at least 1%) in the population
Different mutations in a gene
Can cause the same disorder
Almost always involve a loss of gene function
Recessive mutations
Null allele
Complete loss of function
Partial loss of function
hypomorphic allele
Dominant mutations
Can involve a loss of protein function OR a gain of protein function
Incomplete dominance
A loss of function mutation where mutant phenotype of Aa is between AA and Aa (heterozygotes with one copy of the dominant allele have half the functional gene dosage)
Dominant negative
A loss of function mutation that can interfere with function of the wild type protein
Gain of function mutation
- Enhances the function of the wild type protein
- A new function is created
Antenna mutation in Drosophila
(Dominant) gan of function mutation
Codominance
Heterozygote expresses the phenotypes of both homozygotes
Allelic series
Describes the dominance hierarchy of multiple alleles
Outside Mendel’s garden
- Genes may (and usually) have more than 2 alleles
- Different alleles may affect the phenotype in different ways
- A single gene may control several traits
- Multiple genes may control a single trait
Complementation test
You wan to find out if you have a new mutation in a novel gene, or is it just another allele of an already known mutation so you cross the two mutants together and whatever phenotype you get has to be explained by Mendelian ratios
Phenotypes are influence by
Both genetic and environmental factors
Conditional alleles/mutations
Expressivity is environmentally-dependent
Incomplete penetrance
Individuals do not express a trait even though they have the appropriate genotype
Variable expressivity
A trait is not manifested uniformly among individuals that show it
Central dogma
The two step process transferring of information from DNA to protein (DNA transcription –> Translation –> protein)
Genes encode
One of five known types of RNA
Five known types of RNA
snRNA rRNA tRNA mRNA Pre-miRNA
snRNA
Participates in sliceosome (stays inside nucleus)
rRNA
Ribosomal RNAs transcribed from one of the DNA strands of a gene and provide structural support/catalyze chemical reaction in which amino acids are covalently linked (part of ribosome in cytoplasm)
tRNA
Carry amino acids to complex to allow expansion of polypeptide chain (part of ribosome in cytoplasm)
mRNA
Messenger RNA assembled as a complementary copy of one of the two DNA strands
Nucleotide sequence is complimentary to the of the gene from which it is transcribed
Allows cells to separate information storage from information utilization
Analogy: You make a copy of a page in your textbook so that you can carry the information around with you without carrying textbook so that you don’t lose it
(nucleus and cytoplasm)
Pre-miRNA
Bind to regions (typically 3’ end) and prevent transcription/translation (work in cytoplasm)
Hydroxyl group on 2’ C of ribose
RNA
Template strand
The DNA strand that is copied in transcription to produce a complementary strand of RNA
Non-template strand
The nontranscribed strand of DNA in transcription that will have the same sequence as the RNA transcript except that T is present at positions where U is present in the RNA transcript
DNA template
3’ to 5’ direction
RNA is transcribed
5’ to 3’ direction
RNA polymerase
Enzyme that catalyzes the synthesis of RNA
During transcription the DNA double helix
Is locally unwound
Differences between RNA and DNA?
RNA uses a ribose sugar, DNA uses a deoxyribose sugar RNA uses Uracil, DNA uses Thymine RNA is unstable, DNA is stable RNA is transcribed from DNA Protein is translated from RNA
Why is RNA unstable?
You don’t want mRNA to hang around any longer than it needs to be to be translated so it degrades very rapidly
How does transcriptional machinery know where to begin?
RNA polymerase has to recognize code in DNA
TATA box
A conserved promoter sequence that determined the transcription start site for eukaryotes
Initiation and termination of transcription in prokaryotes and eukaryotes
Are significantly different
Promoter
A nucleotide sequence to which RNA polymerase binds and initiates transcription
Transcription in prokaryote
Initiation: mRNA starts at position 1 , 10 and 35 nucleotides upstream there are promoter regions
Elongation: genes are closely spaced and several can be encoded on a single RNA molecule
Termination: Transcription terminator sequence (Poly A track and hairpin loop) hint for polymerase to jump off
Transcription terminator sequence
Signals end of transcription
Introns
Noncoding sequences located between coding sequences
Pre-mRNA
Introns present
Mature mRNA
Introns are removed
Exons
(Both codon and noncoding sequences) are composed of the sequences that remain in the mature mRNA after splicing
Transcription factor
A protein that regulates the transcription of genes
TATAAT sequence
An AT-rch sequence in prokaryotic promoters that facilitates the localized unwinding of DNA and the initiation of RNA synthesis
Eukaryotic transcription
Initiation: Transcription factor binds to TATA box (promoter region) in order to help assemble transcription machinery
Elongation
Termination: Enzyme cuts strand of RNA, a 5’ cap is added, a tail Poly-A tail is added at the 3’ end of the strand, introns are spliced out
