CHAPTER 19
THE ORGANIZATION AND
CONTROL OF EUKARYOTIC
GENOMES
GENE REGULATION IN
EUKARYOTES IS MUCH MORE
COMPLEX THAN IN PROKARYOTES


EUKARYOTES REQUIRE CELL
SPECIALIZATION S WELL AS CELL
DIFFERNTIATION
EUKARYOTES ALSO HAVE A MUCH
LARGER AND MORE COMPLEX GENOME

STRUCTURE OF CHROMATIN

PROKARYOTIC DNA
USUALLY CIRCULAR
 SMALLER THAN EUKARYOTIC DNA @ ONLY
SEEN WITH AN ELECTRON MICROSCOPE
 ONLY ASSOCIATED WITH A FEW PROTEINS
 SIMPLE – NOT A VERY ELABORATE
STRUCTURE


EUKARYOTIC DNA
COMPLEX WITH A LARGE AMOUNT OF
PROTEIN THAT WILL FORM CHROMATIN
 HIGHLY TANGLED DURING INTERPHASE
 CONDENSED INTO SHORT THICK DISCRETE
CHROMOSOMES DURING MITOSIS
 VISABLE WITH A LIGHT MICROSCOPE
(WHEN STAINED)


HISTONES

RESPONSIBLE FOR THE FIRST LEVEL OF
DNA PACKING

CONTAIN A HIGH PROPORTION OF
POSITIVLEY CHARGED A.A. WHICH WILL
BIND TIGHTLY NEGATIVELY CHARGED DNA



5 TYPES OF HISTONES
SIMILAR FROM ONE CELL TO ANOTHER
SUGGESTING A HIGH CONSERVATION OF
EVOLUTIONARY CHANGES
DNA – HISTONE COMPLEX, IS CHROMATIN IN ITS
FUDAMENTAL FORM (BEADS ON A STRING)

NUCLEOSOMES





BASIC UNIT OF DNA PACKING
FORMED BY DNA WOUND AROUND A PROTEIN CORE
THAT IS MADE UP OF 2 MOLECULES OF 4 DIFFERENT
HISTONES
H2A, H2B, H3, H4, @ H1.
H1 – IS PRESENT ON DNA NEXT TO THE
NUCLEOSOME
MAY CONTROL GENE EXPRESSION BY CONTROLLING
THE ACCESS OF TRANSCRIPTION PROTEINS TO DNA

HIGHER LEVELS OF DNA PACKING

HIGHER ORDER PACKING OF ‘BEADED
STRING’ WILL FORM THE 30nm CHROMATIN
FIBER


WHICH IS TIGHTLEY WOUND COIL, WITH 6
NUCLEOSOMES PER TURN
HISTONE ‘H1’ PULLS THE NUCLEOSOMES INTO A
CYLINDER 30nm IN DIAMETER WHICH FORMS
LOOPED DOMAIN

HETEROCHROMATIN

CHROMATIN THAT REMAINS HIGHLY
CONDENSED CURING INTERPHASE AND
IS NOT ACTIVELY TRANSCRIBED

EUCHROMATIN (TRUE)

LESS CONDENSED DURING INTERPHASE
AND IS ACTIVELY TRANSCRIBED

Ex. BARR BODIES ARE ‘X’ CHROMOSOMES THAT
ARE MOSTLY HETEROCHROMATIN, WHICH HAS A
PARTIAL EFFECT ON GENE EXPRESSION

GENOME ORGANIZATION




MOST DNA DOES NOT ENCODE FOR PROTEINS OR
RNA (97%)
MOST DNA ARE REGULATORY SEQUENCES, THAT ARE
NOT YET TOTALLY UNDERSTOOD. (Ex. INTRONS)
REPETITIVE DNA – 10-15% OF THE GENOME
SATALLITE DNA


HIGHLY REPETITIVE DNA, CONSISTING OF SHORT
UNUSUAL NUCLEOTIDE SEQUENCES THAT ARE
TANDOMLY REPEATED THOUSANDS OF TIMES
DURING ULTRA-CENTRIFUGATION IT SEPARATES DUE
TO THE DIFFERENT DENSITY AND CREATES
‘SATELLITE’ BANDS

TELOMERES
SERIES OF SHORT TANDEM REPEATS AT
THE ENDS OF EUKARYOTIC CHROMOSOMES
 MAINTAIN THE INTEGRITY OF THE LAGGING
DNA STRAND DURING REPLICATION


MUTATIONS CAN EXTEND REPETITIVE
SEQUENCES CAUSING GENES TO MALFUNCTION
 FRAGILE ‘X’
 HUNTINGTONS

INTERSPERSED REPETITIVE DNA


REPRESENT 20-40% OF THE GENOME
REPEATED ELEMENTS THAT ARE
SCATTERED THROUGHOUT THE
GENOME

ALU ELEMENTS




FUNCTION IS NOT TOTALLY
UNDERSTOOD
MADE UP OF 3OO NUCLEOTIDE PAIRS
DO SOME CODING OF RNA
EXCEPTION TO THE IDEA THAT
REPETITIVE DNA IS NON-CODING
MULTIGENE FAMILIES

A COLLECTION OF GENES THAT ARE
SIMILAR OR IDENTICAL IN SEQUENCE.
MORE THAN LIKELY MEMBERS OF EACH
FAMILY EVOLVED FROM A COMMON
ANCESTRAL GENE

PSEUDOGENE

A NONFUNCTIONAL GENE THAT HAS A
DNA SEQUENCE WHICH IS SIMILAR TO
A FUNCTIONAL GENE

Ex. PROMOTORS

GENE AMPLIFICATION @ SELECTIVE
GENE LOSS
SELECTIVE SYNTHESIS OF DNA WHICH
RESULTS IN MULTIPLE COPIES OF A SINGLE
GENE
 MAY TEMPORARILY INCREASE THE NUMBER
OF GENE COPIES AT CERTAIN TIMES


Ex. CANCER CELLS

RETROTRANSPOSONS


SIMILAR TO THE MECHANISM OF A
RETROVIRUS
TRANSPOSABLE ELEMENTS THAT MAY
MOVE WITHIN A GENOME BY MEANS OF
AN RNA INTERMEDIATE

Ex. MORNING GLORY FLOWER COLOR


C=THE CONSTANT REGION, WHICH IS
THE SAME FOR ALL ANTIBODIES, OF A
PARTICULAR CLASS
V=VARIABLE REGION, WHICH GIVES THE
ANTIBODY THE ABILITY TO RECOGNIZE
AND BIND TO A SPECIFIC FOREIGN
MOLECULE

ANTIBODY SPECIFICITY AND DIVERSITY
RESULT FROM THE UNIQUE ORGANIZATION OF
THE ANTIBODY GENE WHICH IS FORMED BY
THE REARRANGEMENT OF THE GENOME
DURING ‘B’ CELL DEVELOPMENT

VARIATION WITHIN
IMMUNOGLOBULINS IS DUE TO:


DIFFERENT COMBINATIONS OF
VARIABLE AND CONSTANT REGIONS IN
THE POLYPEPTIDES
PLUS, DIFFERENT COMBINATIONS OF
POLYPEPTIDES

IMMUNOGLOBULIN
(ANTIBODY)GENES
IMMUNOGLOBULINS ARE PROTEINS THAT
RECOGNIZE SPECIFIC PATHOGENS AND ARE
ABLE TO FIGHT THESE INVADERS
 THEY ARE PRODUCED BY ‘B’ LYMPHOCYTES


CONTROL OF GENE EXPRESSION

REARRANGEMENT OF ANTIBODY GENES
AND OTHER PROCESSES MAY ALTER DNA
SEQUENCES IN SOMATIC CELLS, WHICH
ARE SPECIFIC MECHANISMS TO REGULATE
GENE EXPRESSION


EACH CELL OF A MULTICELLULAR
ORGANISM EXPRESSES ONLY A
SMALL FRACTION OF ITS GENES
 SO
CONTROL OF GENE EXPRESSION
MAY OCCUR AT ANY STEP IN THE
PATHWAY FROM GENE TO
FUNCTIONAL PROTEIN

DNA METHYLATION @ HISTONE

EUKARYOTIC GENES
CONTAIN INTRONS
 CONTAIN PROMOTOR SEQUENCES THAT
MAY BE REGULATED BY




ENHANCERS – NONCODING DNA THAT CONTROL
SEQUENCES THAT ENHANCE A GENES
TRANSCRIPTION
LOCATED THOUSANDS OF BASES AWAY FROM
THE GENE PROMOTOR
ACTIVATOR – TRANSCRIPTION FACTOR THAT
BINDS TO AN ENHANCER @ STIMULATES THE
TRANSCRIPTION OF A GENE

POSTTRANSCRIPTIONAL MECHANISMS IN
GENE EXPRESSION

A CELL IS ABLE TO ‘FINE TUNE’ GENE
EXPRESSION BY USING REGULATORY
MECHANISMS THAT OPERATE AFTER
TRANSCRIPTION



RESPONSE TO ENVIRONMENTAL CONDITIONS
REGLATION OF m-RNA DEGRADATON
PROTEIN SYNTHESIS IS ALSO REGULATED BY mRNA’S LIFESPAN IN THE CYTOPLASM

PROTEIN PROCESSING @ DEG
RADATION

3 FOLD PROCESS OF DEGRADATION OF
A PROTEIN BY A PROTEOSOME
PROTEOSOME – AN ENORMOUS PROTEIN
COMPLEX THAT ‘CHOPS UP’ UNEEDED
CELLULAR PROTEINS
 ESSENTIALLY RECYCLES AMINO ACIDS
 UBIQUITIN – SMALL PROTEIN THAT ‘TAGS’
PROTEIN TO BE TRASHED


MOLECULAR BIOLOGY OF CANCER





ONCOGENES – CANCER CAUSING
GENES
PROTO-ONCOGENES- STIMULATE
NORMAL CELL GROWTH AND DIVISION
MUTATION – CONCERTS A PROTOONCOGENE TO AN ONCOGENE
GENE AMPLIFICATION – MORE COPIES
OF ONCOGENES ARE PRESENT THAN
NORMAL
CHROMOSOMAL TRANSLOCATION – THE

MOLECULAR BIOLOGY OF CANCER



POINT MUTATION – SLIGHT CHANGE IN THE
NUCLEOTIDE SEQUENCE MAY PRODUCE A GROWTH
STIMULATING PROTEIN THAT IS MORE ACTIVE OR
MORE RESISTANT TO DEGRADATION THAN A
NORMAL PROTEIN
TUMOR SUPRESSOR GENE – PROTEINS THEY
ENCODE WILL NORMALLY HELP PREVENT
UNCONTROLLED CELL GROWTH
MULTIPLE MUTATIONS


USSUALLY CANCER DEVELOPES
MORE THAN ONE SOMATIC MUTATION IS NEEDED TO
TRANSFORM NORMAL CELLS TO CANCER CELLS


THE MOLECULAR BIOLOGY OF
COLORECTAL CANCER AND BREAST
CANCER HAVE BEEN FAIRLY WELL
DOCUMENTED TO THIS DATE.
THEY ARE BEST UNDERSTOOD AND
CONSEQUENTLY HAVE THE BETTER
SURVIVAL RATES