Chapter 1 – Genetics the Study of Biological Information

• Complementary base pairs = key feature of DNA molecules

o Bacteria – 90% of DNA codes protein
o Humans – 5% of DNA codes protein
• Chromosomes: organelles that package and manage the storage, duplication, expression,
and evolution of DNA
• Genome: entire collection of chromosomes in each cell
• Protein: long chain of amino acids that create a 3 dimensional structure through folding
• Biological System: complex network of interacting molecules or groups of cells that function
in a coordinated manner through dynamic signaling
o the informational aspect propels a biological system into the 4th dimension
• Genetic Relatedness
o Universality of the genetic code points to the occurenece of a common ancestor
o Development of the Eye
 Originally thought to arise through convergent evolution
 But the study of Pax6 gene indicates that eyes could be a shared ancestral trait
– gene initiates eye developments in both vertebrates ad invertebrates
• Molecular Construction of Genomes has allowed evolution of complexity
o Family of genes arise by duplication of primordial gene  genes diverge from each
other (example: hemoglobin genes)
o Duplication by exon rearrangement  allow old genes to continue to function
o Example: immune system  large amount of genes with slight variations
o Rapid change of regulatory networks that control gene express
• Model Organisms
o E. coli
o S. cerevisae (yeast)
o C. elegans
o D. meanogaster (fruit fly)
o Mus musculus (mouse)
• Genetic Dissection: inactivate a gene and observe consequences
Chapter 2 – Mendel’s Breakthrough: Patterns, Particles, and Principles of Heredity

• Genes: basic unit of biological info

• Heredity: the way genes transmit biochemical, physical and behavioral traits from parent to
offspring
• Genetics: science of heredity, explains the biological structures and mechanisms that
determine what is inherited an how
• Mendel’s Assumptions
o Variation (an expressed in alternative forms of a trait) is widespread in nature
o Observable variation is essential for following genes
o Variation is not distributed solely by chance rather by genetic laws
o Laws of heredity apply equally to all sexually reproducing organisms
• Mendel’s experiment
o Garden peas (normally self-fertilizing) but instead carried out cross fertilization by
brushing pollen on the female organ
o Possessed discrete traits (rather than continuous traits
o Collected and perpetuated lines of true breeding peas – pure breeding lines
o Cross bred pure breeding lines to create hybrids
o Reciprocal crosses – reversed the traits of males and female parents, controlling
whether trait was transmitted via egg or sperm  result: progeny were similar,
disproved that one parent contributes more to the next generation
• Monohybrid Crosses Reveal Units of Inheritance and the Law of Segregation
o Players
Parental (P) Generation – pure-breeding (reciprocal cross between a green
and yellow pea plant)
 First Filial (F1) : arose from monohybrid crosses (hybrids for a single trait)
 Second Filial (F2): cross of the F1 hybrids  3:1 ratio of yellow : green peas
• Reappearance of Recessive Trait Disproves Blending
o Monohybrid cross reveals that yellow = dominant and green trait = recessive
• Law of Segregation: 2 alleles for each trait separate (segregate) during gamete formation
and then unite at random, one from each parent, at fertilization (refers to equal segregation)
• Testcrosses Establish Genotype
o Phenotype: observable characteristic
o Genotype: actual pair of alleles present
 Homogenous: pair of alleles = same - Homozygote
 Heterogeneous: 2 different alleles – Heterozygote
o Testcross: mate an individual with unknown dominant phenotype with a homozygous
recessive individual  if the unknown is a homozygote  then offspring will all display
dominant phenotype. If unknown is a heterozygote  offspring will demonstrate a 3:1
ratio of dominant to recessive phenotypes
• Dihybrid Cross Reveals Law of Independent Assortment: crossed two dihybrid
(heterozygous for 2 separate alleles) to see how two alleles segregate. Counted the
recombinant types and parental types. What resulted were 4 different phenotypes (that
originated from 2 different phenotypes; and 9 different genotypes  observed 9:3:3:1 ratio
o if u looked at just one phenotype  still a 3:1 inheritance ratio
o Law of Independent Assortment: during gamete formation, different pairs of alleles
segregate independently of each other  that way you can use the multiplication rule
 can construct a branched-line diagram
 Find the possible amounts of gametes = 2n , where n = number of alleles
• Family history = pedigree
o Square = male
o Circle = female
o Double connecting line = consanguineous mating (mating btw relatives)
o Vertical pattern of inheritance indicates rare dominant trait  someone in each
generation has the disease
o Horizontal pattern of inheritance indicates rare recessive trait – parents are
heterozygotes (carriers)  yield many offspring in which multiple kids of disease
 Chapter 3 – Extensions to Mendel: Complexities in Relating Genotype to Phenotype

• Incomplete dominance: hybrid resembles neither parent; its novel phenotype is usually an
intermediate between the parental phenotypes
o Red, White, Pink Snapdragons
• Codominance: hybrid shows the traits from both pure breeding parents
o Blood types (ABO)
o Spotted, dotted lentil seed coats
• Variations of complete dominance do not negate Mendel’s Law of Segregation
• Multiple Alleles: genes that have more than two alleles (example ABO blood type  total of
6 combos)
o Dominance series: alleles are listed in order from most dominant to most recessive
 Conduct testcross with all the possible pure breeding phenotypes  yields a
hybrid  recross the hybrid offspring  see F2 offspring ratio  if 3:1, the
phenotype that is more common is dominant  if 1:2:1, the two genotypes are
equally dominant
o Sometimes, in multiple allelic series, each allele is codominant with every other allele
 typical at the molecular level
 Example: histocompatablity antigens
 Multiple alleles arise from mutations (frequency: 1/10,000 to 1/1,000,000)
• Mutations make it possible to follow gene transmission
• It takes at least 2 alleles to see gene transmission
• Allele frequency:
o Total number of copies of a gene = 2 x number of individuals
o Wild type allele: allele frequency greater than 1% (+)
o Mutant allele: allele frequency less than 1%
o Monomorphic: a gene with only one wild type allele
o Polymorphic: a gene with more than 1 wild type
 Example: ABO blood type – all have frequency greater than 1%
• Incompatibility mechanism in plants
o The allele of the egg cell and pollen cell must be different or else fertilization doesn’t
occur  proliferates the development of mutants
• Pleiotropy: single gene determining multiple seemingly unrelated characteristics – not so if
you look at the molecular level
• Recessive lethal allele
o Agouti mice  AA x AAy  3:1 agouti:yellow (recessive lethality in utero)
 AAy x AAy  2:1 yellow:agouti  instead of 3:1
 Yellow (Ay) dominant in producing yellow coat; recessive in producing lethality
o Lethality beyond birth – Tay-Sachs disease

What Mendel Extension Extension’s effect on Extension’s effect on

Described Heterozygous ratios resulting from
Phenotype F1xF1 cross
Complete dominance Incomplete dominance Unlike either Phenotypes coincide
Codominance homozygote with genotypes in ratio
of 1:2:1
Two alleles Multiple alleles Multiplicity of A series of 3:1 ratios
phenotypes
All alleles are equally Recessive lethal alleles No effect 2:1 instead of 3:1
viable
One gene determines Pleiotropy: one gene Several traits affected Different ratios
one trait influences several in different ways, depending on
traits depending on dominance relations for
dominance relations each affected trait
 • Multiple Gene interactions
o Can be seen through a dihybid cross that yields a phenotype ratio besides a 9:3:3:1.
o Complementary gene action: 2 genes work in tandem to produce a trait (9:7 F2
phenotype ratio)
o Epitasis: gene interaction in which the effects of an allele at one gene hide the effects
of alleles at another gene
o Recessive epitasis: homozygosity for a recessive allele of the second gene is
required to hide the effects of another gene (9:3:4 F2 ratio; Labrador retriever coat
colors)
o Dominant epitasis: presence of dominant allele can hide the effects of another gene
(12:3:1 or 13:3)

Gene interaction Example A— B-- A— bb Aa B-- aa bb F2

Phenotypic
Ratio
None: 4 distinct F2 Lentil seed 9 3 3 1 9:3:3:1
phenotypes coat cololr
Complementary: one Sweat pea 9 3 3 1 9:7
dominant allele of each of flower color
two genes is necessary to
produce phenotype
Recessive epistasis: Retriever 9 3 3 1 9:3:4
homozygous recessive of coat color
one gene masks both
alleles of another
Dominant epistasis I: Summer 9 3 3 1 12:3:1
dominant allele of one squash color
gene hides effects of both
alleles of another
Dominant epistasis II: Chicken 9 3 3 1 13:3
dominant allele of one feather color
gene hides effects of
dominant allele of another

• Heterogeneous trait: a mutation at any one of a number of genes can give rise to the same
phenotype (deafness)
o Location of mutation is very difficult to determine
o For deafness – if 2 deaf parents have a kid who can hear  mutations are located on
different genes
• Complementation Test: used to discover whether a particular phnotype arises from
mutations in the same or separate genes
o set up mating btw ind. From 2 lines in which recessive mutations arose independently
 if offspring express wt phenotype, complementation has occurred, meaning
original mutations affected 2 different genes and the normal allele for the same
gene from the parent cannot
 can’t use if the mutation is dominant to the wild type
 noncomplementation – mate two parents with a recessive mutation  all
offspring still display the disease
• penetrance: how many members of a population with a particular genotype show the
expected phenotype. Can be complete (100%) or incomplete
• Expressivity: the degree / intensity with which a particular genotype is expressed in a
phenotype. Can be variable (retinoblastoma, 1 or both eyes can be affected) or unvarying
(pea color)
• Modifier Genes: alter phenotypes produced by the alleles of other genes – a continuum
• Environmental Factors
o Conditional lethal: gene is lethal only under certain conditions
 Permissive range: range of temperatures under which insects remain viable
 Restrictive Range: lethal range
o Phenocopy: change in phenotype arising from environmental agents that mimics the
effects of a mutation in a gene – not heritable and don’t lead to genetic change
• Continuous versus discontinuous trait
o Continuous traits typically require more genes, which yield a larger ranger of variation
o Example: skin color, weight, height
o Continuous traits demonstrate incomplete dominance
o Continuous traits also are called quantitative traits: vary over a range of values and
can usually be measured
o Polygenic; traits controlled by multiple genes and show additive effects of a large
number of alleles
 Polygenic traits are multifactoral, but not all multifactoral traits are poygenic
 Chapter 4 – The Chromosome Theory of Inheritance

• Metacentric chromosome: centromere is in the middle / Acrocentric chromosome:

centromere is close to end
• Cell division – cytokinesis
o Animals – contractile ring and cleavage furrow
o Plants – cell plate
o Syncytium: an animal cell with two or more nuclei (fruit fly embryo)
o coenocyte: multinucleated plant tissue (coconut milk)
• Meiosis
o Prophase I: condensation of chromatin, pairing of homologous chromosome,
reciprocal exchange of genetic info
 Leptotene: definable substage of prophase ; Chromosomes thicken
 Zygotene: conjugation – chromosomes match up and zipped together – called
synapsis om a elaborate protein structure called synaptonemal complex –
aligns homologs with precision
 Pachtyene: completion of synapsis
• Bivalent / Tetrad: synapsed chromosome pair
• X and Y chromosomes don’t synapse completely, but there is a small
region of homology
• Recombination nodules appear along synaptonemal complex
between nonsister chromosomes – allows for recombination and
crossing over
 Diplotene
• Synaptonemal complex dissolve
• Tetrad of 4 chromatids is visible
• Crossover points appear as chiasmata which hold nonsister chromatids
together
• Meiotic arrest occurs at this time in many species
 Diakinesis
• Chromatids thicken and shorten
• Nuclear membrane breaks down and spindles begin to form
• Nondisjunction: homologs of chromosomes do not segregate during meiosis I (Trisomy 21)
• Instances of Recombination
o Prophase I (chromosome recombination)
o Metaphase I (independent assortment)
o Metaphase II
o Telophase II (gamete formation)
• Gametogenesis – gamete formation – requires
o Oogenesis: egg formation
 Oogonia: diploid germ cells in ovar; multiply rapidly to produce primary
oocytes
 Primary oocytes under assymetrical meiosis I  larger cell is the secondary
oocyte (receives 95% of cytoplasm)  smaller cell is polar body
 Secondary oocyte undergoes assymetrical meiosis II  produces an ovum and
another polar body
o Spermatogenesis: sperm formation
 Primary spermatocytes: undergo symmetrical meiosis  secondary
spermatocytes  spermatids  sperm
• Validation of the Chromosome Theory
o Correlates with Mendel’s Laws with Chromosome Behavior During
 1. every cell contains 2 copies of each kind of chromosome and there are 2
copies of each kind of gene
  2. the chromosome complement, like Mendel’s genes, appears unchanged as it
is transmitted from parents to offspring through generations
 3. During meiosis, homologous chromosomes pair and then separate to diff
gametes just as the alternative alleles of each gene segregate to different
gamets
 4. Maternal and paternal copies of each chromosome pair separate to opposite
spindle poles without regard to assortment of any other homologous
chromosome pair, just as the alternative alleles of unrelated genes assort
independently
 5. at fertilization, an egg’s set of chromosomes unites with a randomly
encountered sperm’s set of chromosomes, just as alleles obtained from one
parent unite at random with those from the other parent
 6. In all cells derived from the fertilized egg, one-half of the chromosomes and
one half of the genes are of maternal origin, the other half of paternal origin
• X-linked: a gene that is carried on the X chromosome (example: red vs. white eyes in fruit
flies)
o Hemizygous: condition of male fruit flies because their diploid cells have half the
number of alleles carried by the females on her two X chromosomes – a single white
gene on the X chromosome of a male will cause the male to have white eyes, while in
the case of a female, they would have red eyes
o Criss-Cross Inheritance: white female x red male  all white males (2 opposite
genotypes)
1. trait appears in more males than females since a female has to receive two copies of
the rare defective allele to show it, whereas a hemizygous male with only one copy will
display the phenotype
2. the mutation and trait never pass from father to son because sons receive only a Y
chromosome from their fathers
3. an affected male does pass the X-linked mutation to all his daughters who serve as a
heterozygous carriers not manifesting the trait but passing it onto their offspring. One
half of the sons of the carrier females will inherit defective allele and trait
4. thus, the trait often skips a generation as the mutation passes from grandfather
through a carrier daughter to grandson
5. only time the trait appears in successive generations is when a sister of an unaffected
male is a carrier. Then one half of her sons will show the trait
Autosomal Genes can be used to determine differences between sexes
• Sex-limited traits
o Govern traits that appear in one sex but not in other – aka traits that are expressed
diff in 2 sexes
o Affect a structure / process that is found in one sex but not in other
o Mutations can only influence only the phenotype of the sex that expresses those
structures or processes
o Drosophila male’s with recessive stuck mutation die during copulation; females are
unaffected
• Sexually Influenced traits
o Show up in both sexes but expression of such traits may differ b/c of hormonal
differences
o Example: pattern baldness – dominant allele  heterozygous (only men affected);
homo (both but women bald later)
Chapter 5 – Linkage, Recombination, and the Mapping of Genes on Chromosomes

See Written Notes

Chapter 6 – DNA: How the Molecule of Heredity Carries, Replicated, and Recombines Info

See Written Notes

 Chapter 7 Anatomy and Function of a Gene: Dissection Through Mutation

• Forward Mutation; a mutation that changes a wild type allele of a gene to a different allele
o Notation: A+  a (recessive mutation) / b+  B (dominant mutation
• Reverse Mutation: mutation that changes a novel mutant allele to revert back to wild type
o Notation: a  A+ or B  b+
o Wild type always denoted with a +
• Mutation Classification
o Substitution
o Deletion
o Insertion
o Inversions
o Reciprocal translocations
o Chromosomal rearrangements
• Spontaneous mutation influencing phenotypes occur at a very low rate
o Mutation rate varies from gene to gene
o Average mutation rate is 2-12e-6
o Forward mutation usually occur more often than reverse mutations
o Transposable Elements: forward mutations caused by transposable elements revert
to wild type at a higher rate
• Colony results from a single antibiotic resistant bacterium – thus all have the same genetic
make up
• Luria-Delbruck fluctuation experiment – or gins of bacterial resistance
o Hypothesis 1: if resistance arises only after exposure to a bactericide, all bacterial
cultures of equal size should produce roughly the same number of colonies
o Hypothesis 2: If random mutations conferring resistance arise before exposure to
bactericide, the number of resistant colonies in different cultures should vary widely
o Actual: large fluctuations suggest that mutations in bacteria occur as spontaneous
mistakes independent of exposure to a selective agent
Hydrolysis, Radiation, ultraviolet light, and oxidation can alter the information stored in
DNA
• Depurination: hydrolysis of a purine base (A or G)
o Apurinic site can’t specify the complementary base, the DNA replication introduces a
random base opposite the apurinic site, causing a mutation in new complementary
strange ¾ of the time
• Deamination: removal of an amino group, changes cytosine to uracil (CU); U complements
with A instead of G
• X-ray Radiation cause the phosphate sugar backbone to break
• UV causes adjacent thymine residues to become chemically linked into thymine-thymine
dimmers
Dealing with these Problems
• Excision Repair: specialized proteins patrol for irregularities and take out damaged bases,
DNA polymerase fills in the gaps
• Methyl directed mismatch repair: uses redundancy of DNA double strands to restore info;
recognizes base pairs mismatched during replication
• Instability of Trinucleotide Repeats causes mutations
o CAG, CTG, GAA, CGG are unstable soothe number of repeats often increases or
decreases in different cells of the same individual  such as gametes
• Mutagen: any physical or chemical agent that raises the frequency of mutations above the
spontaneous rate
• Base analogs: similar to normal nitrogenous bases that replication machinery can
incorporate them into DNA in place of the normal bases – can cause base substituions on the
complementary strand that is synthesized
 • Intercalator mutagenesis compounds: flat planar molecules that can sandwich
themselves between successive base pairs and disrupt the machinery for replication,
recombination or repair  generate deletions or insertions
• Mugatgens and their Actions
o Replace a base – base analogs have a chemical structure almost identical to that of a
DNA base – cause substitution
o Alter base structure and properties – cause substitution
 Hydroxylating agents: adds hydroxyl group
 Alkylating agents: adds ethyl or methyl groups
 Deaminating agents: removes amine groups
o Insert between bases: intercalating agents – cause insertions
Complementation testing reveals whether two mutations are in the same or different
genes
• Several mutation on one wt gene observed figure out whether mutation are on multiple genes
or just one
• Experiment: 2 mutants are cross  F1 expresses wt, mutations are present on 2 genes that
work to express the phenotype, these two genes make up a complementation group
• Complement group: a collection of mutations that do not complement each other; synonym
for gene
• Experiment: 2 mutants are crossed  F1 expresses recessive phenotype  mutations located
on same gene
• Make a complementation table to help
A Gene is a Linear Sequence of Nucleotide Pairs that can Mutate Independently and
Recombine with Each other (Review)
• The following experiments proved that F1 that expresses wt can still mean that mutation was
located on one gen, because recombination can occur with in a gene
• Experiment: Analyzing Multiple rII—mutations of Bacteriophage T4
o Lawn
o Plaque
o Fine structure mapping
• Using Deletions to Map Mutation and Define a Gene
• There a Mutation hot spots where point mutations occur frequently
• One gene, one enzyme hypothesis: A gene contains info for producing a specific
enzyme
o Biochemical pathway: the orderly series of reactions that allows Neurospora to
obtain simple molecules from the environment and convert them step by step into
successively more complicated molecules and eventually it’s final product
o Auxotroph: mutant microorganism that can grow on minimal medium only if it has
been supplemented with one or more growth factors not required by wild-type strains
o Prototroph: wild type cell that can synthesize a particular growth factor and thus
grow in the absence of minimal medium  refers to the
o Think biochemical pathways lab  intermediates, feeding, feeders, end product,
different branches
Dominance Relations Between Alleles Depend on Relation between protein functions and
phenotype
• Alleles that produce nonfunctional proteins are often recessive
o Null mutations / alleles: mutations that abolish function of protein encoded by the
wild type allele
o Hypomorphic mutation: produces either much less of the protein or a protein with
very weak but detectable funcation
• Incomplete dominance can arise when the phenotype varies in proportion to the amount of
functional protein
• Dominance can reflect several kinds of phenomena
o Haploinsufficiency: situations in which one wild type allele does not provide enough
of a gene product. Only a minority of phenotypes are so sensitive to the amount
o Hypermorphic mutation: produces an allele generating either more protein than the
wild-type allele or the same amount of a more efficient protein, making the
hypermorphic allele dominant
o Dominant negative alleles: alleles of subunits of multimers that block the activity of
the subunits produced by normal alleles;
o Neomorphic mutations: rare class of dominant alleles that arise from these that
generate a novel phenotype
o Ectopic Excpression: production of a protein outside of its normal place or time
Chapter 8 – Gene Expression: The Flow of Genetic Information from DNA via RNA to
Protein

• DNA  transcription  mRNA  Translation  Polypeptide

• A Codon is composed of three nucleotides and the starting point of each gene establishes the
reading frame
• The Genetic Code
o Code consists of triplet codons, each of which specifies an amino acid. The code shows
the 5’ to 3’ sequence of the 3 nucleotides in each mRNA codon, the first nucleotide
depicted is at the 5’ end of the codon.
o The codons are nonoeverlapping. In the mRNA sequence 5’ GAAGUUGAA 3’, the first
3 nucleotides form one codon. Nucleotides 4 through 6 form a second codon
o The code is degenerate, in many cases more than one codon specifies the same
amino acid, but the code is unambiguous
o In the reading of a transcript of a gene, the cellular machinery scans a single strange
of mRNA from a fixed starting point that establishes a reading frame. AUG is the
start codon
o Moving from 5’ to 3’ end of an mRNA each successive codon is sequentially interpreted
into amino acid starting at the N terminus moving toward the C terminus
o Mutations may modify the message encoded in a 3 ways:
 Frameshift mutations: insertions / deletions, changes reading frame
 Missense Mutations: change a codon for one amino acid to a different amino
acid.
 Nonsense mutation: changes codon for an amino acid to a stop codon
• Translation – see featured figure
o Transcriptional difference between prokaryotes and eukaryotes
o In Eukaryotes, RNA processing after transcription produces a mature mRNA
o Adding a methylated cap at the 5’ end and a Poly-A-Tail at the 3’ end
 Methyl transferase capping enzymes added to the primary transcript 5’ end.
This adds methyl groups to the backward G to form a methylated cap
 3’ end does not encode, consists of 100-200 As, aka Poly-A-Tail, the A’s are
added by poly-A polymerase which adds to the 3’ end after cleavage
o RNA splicing removes introns from the primary transcript
 Exons are what are left and are the expressed regions
 RNA splicing: the procress that deletes introns and joins together successive
exons to forma mature mRNA
 3 types of short sequences on the primary transcript to help ensure specificity
of splicing:
• Splice donors: where 3’ end of exon abuts the 5’ end of intron
• Splice acceptors: at 3’ end of intron where it joins to the next exon;
the final nucleotides of the intro are always AG (arrows, preceded by 12-
14 pyrimidines
• Branch sites: located within the intron about 30 nucleotides upstream
of the splice acceptor, must include an A (arrow), rich in
pyrimidines
 2 sequential cuts, first at splice donor site and second at splice-acceptor site
remove intron
 After the first cut, a lariat structure is formed (loop sctructure)
 Splicing requires splicesomes, makes sure splicing occurs in concert
• 4 subunits of ribonucleo-proteins (snRNPs “snurps”)
• snRNPs contain snRNAs (small nuclear RNA)  pair with splice donor
and acceptor sequence  specificity
  Ribozyme: primary transcripts that can splice themselves without aid of
spliceosome
 Possible purpose: allow for making possible to assemble genes from various
exon building blocks  leading to genetic diversity  exon shuffling
o Alternative splicing producing different mRNAs from the same primary transcript
 A mechanism for antibody variation and proliferation
 Trans-splicing: exons from different genes were combined to form a mature
transcript
Transfer RNAs Mediate the Translation of mRNA codons to Amino Acids
• tRNA: short RNA molecules that carries a particular amino acid and an anticodon that only
complements a segment of the mRNA
• levels:
o 1. primary structure: nucleotide sequence of tRNA
o 2. secondary: short complementary regions within tRNA’s single strand can form base
pairs with each other to create cloverleaf shape
o 3. tertiary: 3 dimensional folding looks like compact letter L
o Aminoacyl-tRNA synthase: catalyze reactions that attach amino acid attachment
(very specific)
o Charged tRNA: tRNA coupled with amino acid
• Base pairing between an mRNA codon and a tRNA anticodon directs amino-acid incorporation
into a growing peptide
• Wobble: some tRNAs can recognize more than one codon; flexibility in base pairing between
3’ nucleotide in the codon and 5; nucleotide in the codon
o 61 possible codon triplets; 42 tRNAs, 16 possible combinations not represented
o Often the 5’ nucleotide on the tRNA can pair with more than one kind of nucleotide on
the mRNA
Ribosomes are sites of polypeptide synthesis
• Ribosomes are complex structures composed of rRNA and protein
• Different partos ribosome have different functions
o Peptidyl transferase: larger 50S subunit – catalyzes formation of peptide bonds
joining adjacent amino acids
o Peptidly (P) site and aminoacyl (A) site: simultaneously bind to 2 different tRNA
molecules
Mechanism of Translation
• Initiation
• Elongation
• Termination
Processing after Translation can change a polypeptide’s structure
• Polyprotein: before cleavage
• Posttranslational modification: addition of chemical constituents, phosphates, methyl,
carbohydrates
How mutations affect gene expression
• silent mutations – don’t affect amino acid specified
• missense mutation – replace one amino acid with another
• nonsense mutations – change an amino acid specifying codon to a stop codon
• frameshift mutation – result from insertion of deletion of nucleotides within coding
sequence
• mutations altering genes encoding proteins or RNAs involved in gene expression are usually
lethal
• mutilations in tRNA genes can suppress mutations in protein-coding genes (double mutations
that compensate for each other)
o nonsense suppressor tRNAs: that result from tRNA gene mutation
o cells with this condition can only survive if both mutations exist
The cellular components of Gene expression
• Transcription
o Core RNA polymerase
o Sigma subunit
o Rho factor
• Splicing and RNA processing
o ssRNAs
o Protein components of spliceosomes
o Additional splicing factors
o Capping enzyme
o Methyl transferases
o Poly-A polymerase
• Translation
o mRNAs
o tRNAs
o Aminoacyl-tRNA synthetases
o rRNAs
o Protein components of ribosomes
o Translation factors
• Protein Processing
o Deformylase
o Amino peptidases
o Proteases
o Methylases
o Hydrolzylases
o Glycosylases
o Kinases
o Phosphatase

Chapter 10: Reconstructing the Genome through Genetic and Molecular Analysis

• Genomicists look at Genome’s sequence and polymorphisms (allele variations)

• Heterochromic DNA is not clonable and thus cannot be sequenced
• 10=fold sequence coverage – when checking to see you have the correct sequence (correct
insert in clone) – take at least 10 clones to sequence, which accounts for any errors
• Sequencing Techniques
o Cloning
o Hybridization
o PCR amplification
o DNA sequencing (Sanger method – 4 different dNTPs + ddNTPs and colored labeled)
o Computational Tools
• Noncoding RNA Genes
o Transfer RNAs (tRNAs): adaptors that translate triplet code of RNA nto amino acid
sequence of proteins
o Ribosomal RNAs (rRNAs): ribosome components
o Small nucleolar RNAs (snoRNAs): required for rRNA processing and base
modifications in the nucleolus (genome are rich with RNA)
o Small nuclear RNAs (snRNAs): spliceosome components
• Increase in Complexity arising from:
o More genes
o Shuffling, increase or decrease of functional modules
 Domain architecture: the number and order of a protein’s domains
o More paralogs through gene duplication
o Alternative RNA splicing
o Chemical modification of proteins
• Five repeat sequence Classes
o Transposon derived repeats (45% of genome)
o Processes pseudogenes – inactive copies of protein coding genes and small structural
RNAs (lack intrans and regulatory sequences; arise by retroposition or copying RNA
into DNA and random integration of cDNA into chromosomes)
o SSR’s of short multimers two or five nucleotides in length such as AA , AT, GCC (3% of
genome)
o Segmenal duplications of 10-300 kb copied from one region to another region of the
genome
o Blocks and repeated sequences at the centromers, telomeres and other chromosomal
features
• Types of Gene Organization
o Gene Families
o Gene-Rich Regions
o Gene Deserts
Aneuploidy
• Mosaicism for aneuploidy: mitosis nondisjunction and chromosome loss
o Mitotic nondisjunction
 Nondisjunction of one set of sister chromatids at anaphase produces aneuploidy
daughter cell
• Trisomic cell
• Monosomic cell
o Mitotic chromosome loss
 Lagging chromatid at anaphase is lost  aneuploidy daughter cell produced
• Monosomic cell
• Normal diploid
o Less severe than nondisjunction that in meiosis
• X—chromosome Mosaicism can produce a Gynandromorph
o Zygote and left half of fly: w+m+/wm
o Chromosome loss in early mitotic division of zygote produces XO cells that are wm
(right half of fly)
• Klinefelter Syndrome (47, XXY)
o Aneuploidy in sex chromosome are less lethal than in autosomes
o Why doesn’t the extra X chromosome get turned off?
 X Chromosome Inactivation
• Not all A-linked genes are inactivated by X chromosome inactivation
o Xist RNA inactivates X chromosome
o Some X genes expressed twice the level of normal males
• Turner Syndrom (45, X)
o Sterile – many patients are mosaics
• X-chromosome reactivation
o Previously inactivated X chrom must be reactivated in the oogonia (female germline
cells prior to meiosis) so that every ovum receives an active X chromosomes
o Infertility of women with turner syndrome might reflective X reactivation: their oogonis
here only have one active X instead o the normal 2
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