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 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, 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 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 HISTONE ACETYLATION, MAY MODIFY CHROMATIN

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 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 m- RNA’S LIFESPAN IN THE CYTOPLASM

PROTEIN 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 PROTO- ONCOGENE TO AN ONCOGENE GENE AMPLIFICATION – MORE COPIES OF ONCOGENES ARE PRESENT THAN NORMAL CHROMOSOMAL TRANSLOCATION – THE MOVEMENT OF DNA WITHIN THE GENOME

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