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9.1 Introduction to Genetics and Genes: Unlocking the Secrets of Heredity
î 
: the study of the inheritance ( 
) of living things
J aransmission of traits from parent to offspring
J Expression and variation of those traits
J ahe structure and function of the genetic material
J How this material changes
î aakes place on several levels: organismal, chromosomal, molecular
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î must be able to self-replicate
î must be accurately duplicated and separated from each daughter cell
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î ahe sum total of genetic material of a cell
î mostly in chromosomes
î Can appear in nonchromosomal sites as well
î In cells- exclusively DNA
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J A discrete cellular structure composed of a neatly packed DNA molecule
î Eukaryotic chromosomes
J DNA molecule tightly wound around histone proteins
J Located in the nucleus
J Vary in number from a few to hundreds
J Can occur in pairs (diploid) or singles (haploid)
J Appear linear
î Bacterial chromosomes
J Condensed and secured by means of histonelike proteins
J Single, circular chromosome

î A certain segment of DNA that contains the necessary code to make a protein or RNA molecule
î Structural genes: code for proteins
î Code for RNA
î Regulatory genes: control gene expression
î Sum of all types is an organisms —
î ahe expression of the genotype creates traits- the  
î All organisms contain more genes in their genotype than are manifested as a phenotype at a given time
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î Vary greatly in size
J Smallest viruses- 4 or 5 genes
J 


 - 4,288 genes
J Human cell- 20,000 to 25,000 genes
î ahe stretched-out DNA can be 1,000 times or more longer than the cell
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î 1953: James Watson and Francis Crick
J Discovered DNA is a gigantic molecule
J A type of nucleic acids
J With two strands combined into a double helix

 
î Basic unit: 

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î Covalently bond to form a sugar-phosphate linkage- the backbone of each strand
î Each sugar attaches to two phosphates
î One bond is to the 5͛ carbon on deoxyribose
î ahe other is to the 3͛ carbon

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î 
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î Attach by covalent bonds at the 1͛ position of the sugar
î Span the center of the molecule and pair with complementary bases from the other strands
î ahe paired bases are joined by hydrogen bonds
J Easily broken
J Allow the molecule to be ͞unzipped͟
î 
 always pairs with  

î 

 always pairs with 




 
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î One side of the helix runs in the opposite direction of the other
î One helix runs from 5͛ to 3͛ direction
î ahe other runs from 3͛ to 5͛
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î Arrangement of nitrogenous bases
J maintains the code during reproduction (conservative replication of DNA)
J Provides variety
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î ahe process of the genetic code duplicated and passed on to each offspring
î must be completed during a single generation time
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î Requires the actions of 30 different enzymes
J Separate the strands
J Copy its template
J Produce two new daughter molecules



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î Each daughter molecule is identical to the parent in composition, but only one strand is completely new
î ahe parent DNA molecule uncoils
î ahe hydrogen bonds between the base pairs are unzipped
J Separates the two strands
J Exposes the nucleotide sequence of each strand to serve as templates
î awo new strands are synthesized by attachment of the correct complementary nucleotides to each single-
stranded template
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î Origin of replication
J Short sequence
J Rich in A and a
 J Held together by only two H bonds rather than three
J Less energy is required to separate the two strands
î Helicases bind to the DNA at the origin
J Untwist the helix
J Break the hydrogen bonds
J Results in two separate strands
 
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î Synthesizes a new daughter strand using the parental strand as a template
î ahe process depends on several other enzymes as well, but key points about DNA polymerase III:
J Nucleotides that need to be read by DNA polymerase III are buried in the double helix- so the DNA must
first be unwound and the two strands separated
J DNA polymerase III is unable to begin synthesizing a chain of nucleotides but can only continue to add
nucleotides to an already existing chain
J DNA polymerase III can only add nucleotides in one direction, so a new strand is always synthesized from
5͛ to 3͛
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î As replication proceeds, the newly produced double strand loops down
î DNA polymerase I removes RNA primers and replaces them with DNA
î When the forks come full circle and meet, ligases move along the lagging strand
J Begin initial linking of the fragments
J Complete synthesis and separation of the two circular daughter molecules
î Occasionally an incorrect base is added to the growing chain
î most are corrected
î If not corrected, result in mutations
î DNA polymerase III can detect incorrect, unmatching bases, excise them, and replace them with the correct base
î DNA polymerase I can also proofread and repair

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î Central dogma
J Genetic information flows from DNA to RNA to protein
î ahe master code of DNA is used to synthesize an RNA molecule (


)
î ahe information in the RNA is used to produce proteins (


)
î Exceptions: RNA viruses and retroviruses
J Recently shown to be incomplete
î In addition to the RNA that produces protein, other RNAs are used to regulate gene function
î many of the genetic malfunctions that cause human disease are found in these regulatory RNA
segments
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î ahe ariplet Code and the Relationship to Proteins
J ahree consecutive bases on the DNA strand- called triplets
J A gene differs from another in its composition of triplets
J Each triplet represents a code for a particular amino acid
J When the triplet code is transcribed and translated, it dictates the type and order of amino acids in a
polypeptide chain
î A protein͛s primary structure determines its characteristic shape and function
î Proteins ultimately determine phenotype
î DNA is mainly a blueprint that tells the cell which kinds of proteins and RNAs to make and how to make them
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î Number of components participate, but most prominent:
J mRNA
J tRNA
J regulatory RNAs
J ribosomes
J several types of enzymes
J storehouse of raw materials
î RNAs: aools in the Cell͛s Assembly Line
J RNA differs from DNA
î Single stranded molecule
î Helical form
î Contains 

 instead of thymine
î ahe sugar is ribose
J many functional types, from small regulatory pieces to large structural ones
J Only mRNA is translated into a protein molecule
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î A transcript of a structural gene or genes in the DNA
î Synthesized by a process similar to synthesis of the leading strand during DNA replication
î ahe message of this transcribed strand is later read as a series of triplets ()
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î Also a copy of a specific region of DNA
î It is uniform in length (75-95 nucleotides long)
î Contains sequences of bases that form hydrogen bonds with complementary sections of the same tRNA strand
î At these points the molecule bends back upon itself into several hairpin loops, giving the molecule a cloverleaf
structure that then folds into a complex, 3-D helix
î Bottom loop of the cloverleaf exposes a triplet (the

) that designates the specificity of the tRNA and
complements mRNA͛s codons
î At the opposite end of the molecule is a binding site for the animo acid that is specific for that anticodon
î For each of the 20 amino acids there is at least one specialized type of tRNA to carry it
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î ahe prokaryotic (70S) ribosome composed of tightly packed rRNA and protein
î ahe rRNA component is a long polynucleotide molecule
î ahe interactions of proteins and rRNA create the two subunits of the ribosome that engage in final translation of
the genetic code
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î All of the elements needed to synthesize a protein are brought together on the ribosomes
î Five stages: initiation, elongation, termination, protein folding, and protein processing
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î mRNA molecule leaves DNA transcription site
î Is transported to ribosomes in the cytoplasm
î Ribosomal subunits are specifically adapted to assembling and forming sites to hold the mRNA and tRNAs
î Prokaryotic ribosomes
J 70s size
î 50s subunit
î 30s subunit
î Eukaryotic ribosomes
 J 80s
î 60s subunit
î 40s subunit
î ahe small subunit binds to the 5͛ end of the mRNA
î Large subunit supplies enzymes for making peptide bonds on the protein
î ahe ribosome scans the mRNA by moving in the 5͛ to 3͛ direction along the mRNA
î ahe first codon is the SaARa codon (AUG but can rarely be GUG)
î With the mRNA message in place on the ribosome, the tRNAs the enter with their amino acids
J ahe complementary tRNA meets with the mRNA code
J Guided by the two sites on the large subunit called the P site and the A site
J ahe E site is where used tRNAs are released
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î ahe mRNA codons and the amino acids they specify
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 of the genetic code: a particular amino acid can be coded for by more than a single codon
î Wobble: in many cases, only the first two nucleotides are required to encode the correct amino acid- thought to
permit some variation or mutation without altering the message
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î Brought about by the presence of a termination codon: UAA, UAG, and UGA
î Often called nonsense codons
î Do not code for a tRNA
î When reached, a special enzyme breaks the bond between the final tRNA and the finished polypeptide chain,
releasing it from the ribosome






î Before it is released from the ribosome it starts to fold upon itself to achieve its biologically active tertiary
conformation
î Posttranslational modifications may be necessary
J Starting animo acid clipped off
J Cofactors added
J Join with other proteins to form quaternary levels of structure
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î Start codon is also AUG, but it codes for a different form of methionine
î Eukaryotic mRNAs code for just one protein
î ahe presence of the DNA in the nucleus means that eukaryotic transcription and translation cannot be
simultaneous
î mRNA in eukaryotes must pass through pores in the nuclear membrane and be carried to the ribosomes in the
cytoplasm for translation
î most eukaryotic genes do not exist as an uninterrupted series of triplets coding for a protein
J &- sequences of bases that do not code for protein
J "- coding regions that will be translated into protein
J Called a split gene- requires further processing before translation
J aranscription of the entire gene with both exons and introns occurs first, producgin a pre-mRNA
J A series of adenosines is added to the mRNA molecule (protects it and directs it out of the nucleus)
J A splicesome recognizes the exon-intron junctions and enzymatically cuts through them
J ahe exons are joined end to end
J Some introns do code for cell substances (in humans, introns represent 98% of the DNA)
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î Diverse
î Some- nucleic acid is linear; others, circular
î most exist in a single molecule, but in a few it is in several
î most contain dsDNA or ssRNA, but other patterns exist
î In all cases:
J Viral nucleic acid penetrates the cell
J ahe nucleic acid is introduced into the host͛s gene-processing machinery
J ahe virus instructs the host͛s machinery to synthesize large numbers of new virus particles
J Viral mRNA is translated into viral proteins on host cell ribosomes using host tRNA

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î Control mechanisms ensure that genes are active only when their products are required
J Enzymes are produced as they are needed
J Prevents the waste of energy and materials
J Antisense RNAs, micro RNAs, and riboswitches provide regulation in prokaryotes and eukaryotes
î Prokaryotes organize collections of genes into 
J Coordinated set of genes regulated as a single unit
J Either inducible or repressible
î Inducible- the operon is turned in by the substrate of the enzyme for which the structural genes
code
î Repressible- contain genes coding for anabolic enzymes; several genes in a series are turned off
by the product synthesized by the enzyme
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î Best understood cell system for explaining control through genetic induction
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î Regulates lactose metabolism in 


 
î ahree important features:
J ahe —
 (a gene that codes for a protein capable of repressing the operon [a ])
J ahe control locus
î - recognized by RNA polymerase
î %
- a sequence that acts as an on/off switch for transcription
J ahe structural locus, made up of three genes eaech coding for a different enzyme needed to catabolize
lactose
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î Normally the operon is in the ͞on͟ mode and will be turned ͞off͟ only when the nutrient is no longer required
î ahe excess nutrient serves as a  needed to block the action of the operon
î Example, 
operon




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î Some infection therapy is based on the concept that certain drugs react with DNA, RNA, or ribosomes and alter
genetic expression
î Based on the premise that growth of the infectious agent will be inhibited by blocking its protein-synthesizing
machinery selectively
î Drugs that inhibit protein synthesis exert their influence on transcription or translation
î Antibiotics often target the ribosome- inhibiting ribosomal function and ultimately protein synthesis
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î Genetic change is the driving force of evolution
î 

: when phenotypic changes are due to changes in the genotype
î An alteration in the nitrogen base sequence of DNA
î ·
: a microorganism that exhibits a natural, nonmutated characteristic
î 


: when a microorganism bears a mutation
J Useful for tracking genetic events,
J Unraveling genetic organization, and
J Pinpointing genetic markers
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: random change in the DNA arising from errors in replication
î &

: results from exposure to known mutagens
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î 


: involve addition, deletion, or substitution of single bases
J


: any change in the code that leads to placement of a different amino acid
î Can create a faulty, nonfunctional protein
î Can produce a protein that functions in a different manner
î Can cause no significant alteration inI protein function
J 

: changes a normal codon into a stop codon
J 


: alters a base but does not change the amino acid and thus has no effect
J #
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: when a gene that has undergone mutation reverses to its original base composition
î 

mutations: mutations that occur when one or more bases are inserted into or deleted from a newly
synthesized DNA strand
J Changes the reading frame of the mRNA
J Nearly always result in a nonfunctional protein
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î most ordinary DNA damage is resolved by enzymatic systems specialized for finding and fixing such defects
î DNA that has been damaged by UV radiation
J Restored by photoactivation or light repair
J DNA photolayse- light-sensitive enzyme
î Excision repair
J Excise mutations by a series of enzymes
J Remove incorrect bases and add correct one
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î Rapid screening system
î Detects chemicals with carcinogenic potential
î Any chemical capable of mutating bacterial DNA can similarly mutate mammalian DNA



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î mutations are permanent and inheritable
î most are harmful but some provide adaptive advantages

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î $


: when one bacterium donates DNA to another bacterium
î ahe end result is a new strain different from both the donor and the original recipient
î Bacterial plasmids and gene exchange
î $

 organism: Any organism that contains (and expresses) genes that originated in another organism
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î Usually involves small pieces of DNA (plasmids or chromosomal fragments)
î Plasmids can replicate independently of the bacterial chromosome
î Chromosomal fragments must integrate themselves into the bacterial chromosome in order to replicate
î ahree means of genetic recombination in bacteria
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, or 
- bear genes for resisting antibiotics
î Can confer multiple resistance to antibiotics to a strain of bacteria
î R factors can also carry resistance to heavy metals or for synthesizing virulence factors


 

 



 
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J Later studies supported this
J Nonspecific acceptance by a bacterial cell- transformation
J Facilitated by special DNA-binding proteins on the cell wall
J Competent cells- capable of accepting genetic material
J Useful for certain types of recombinant DNA technology
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î Contain DNA that codes for the enzymes needed to remove and reintegrate the transposon at another site in the
genome
î Insertion elements- tranposons that consist of only two genetic sequences
î Retrotransposon- can transcribe DNA into RNA and back into DNA for insertion in a new location
î Overall effect- scrambles the genetic language
î In bacteria, involved in:
J Changes in traits such as colony morphology, pigmentation, and antigenic characteristics
J Replacement of damaged DNA,
J Intermicrobrial transfer of drug resistance