THE MARVELS OF DNA
THE STUDY OF DNA
I HAVE A SET OF DVDs ON GENETICS AND DNA, BY A PhD GUY, FROM “THE TEACHING COMPANY.”
IT IS 24 HALF HOUR LECTURES.
GENETICS IS TRULY MIND-BLOWING!
HOW ANYONE STUDYING THIS CAN STILL DECLARE “THERE IS NO GOD” JUST MAKES ME SHAKE MY HEAD IN BEWILDERMENT THAT PEOPLE CAN STILL FOOL THEMSELVES INTO BELIEVING THERE IS NO GOD.
BUT OF COURSE THE BOTTOM LINE IS THAT THEY DO NOT WANT TO BELIEVE THERE IS A GOD, BECAUSE IF THEY DO, THE NEXT COMMON STEP WOULD BE ADMITTING GOD CAN THEN INSPIRE A BOOK TO BE WRITTEN, THAT TELLS US HOW WE SHOULD BE LIVING.
DNA….. FROM THE FIRST LECTURES:
DNA IS INSIDE A GENE.
WE HAVE 24,000 GENES IN THE HUMAN BODY.
DNA IS LONG STRANDS = POLYMER [BEADS ON A CHAIN]
THE BEADS ARE MONOMER [MILLIONS OF UNITS]
4 NITROGEN BASES MAKE UP DNA.
ADENINE = A
THYMINE = T
GUANINE = G
CYTOSINE = C
MANY DIFFERENT ORDER OF THE BEADS IN DIFFERENT AMOUNTS.
PHOEBUS LEVENE [1869 - 1940] — SPENT 30 YEARS STUDYING DNA.
HE DISCOVERED THE BEADS WERE ATTACHED TO A BACK-BONE— A SUGAR-PHOSPHATE BACK-BONE.
ONE OF HIS STUDENTS CALLED IT DEOXYRIBONUCLIAC ACID = DNA.
SO THIS IS LIKE:
A GOLD CHAIN FROM WHICH HAND LITTLE CHAINS AND THE BEADS ARE ON OR HANG FROM THE LITTLE CHAINS.
THE BACK-BONE IS THE GOLD CHAIN.
THE BASES OR BEADS ARE—— A T G C
LEVENE SAID THE CHAIN IS VERY, VERY, VERY, VERY LONG WITH REPEATING UNITS. HE SAID THE REPEATING UNITS WERE A T G C.
HENCE—— ATGCATGCATGCATGC—— FOR HIM IT WAS VERY BORING REPEAT OF UNITS.
HENCE IF HE WAS CORRECT IT LACKED THE KEY TO GENE INTELLIGENCE; WITH 24,000 GENES WITH SOMETHING AS BORING AS THAT COULD NOT GIVE THE EXPRESSION TO COMPLICATE LIFE STRUCTURES.
LEVENE WAS A TOWERING PERSONALITY AND A STUPENDOUS CHEMIST; PEOPLE BELIEVED HIM AND SAID DNA IS OUT AS KEY TO COMPLICATED LIFE STRUCTURES.
THIS WAS THE 1930s.
IN THE LATE 1940s ERWIN CHARGAFF [1905 - 2002] ANOTHER CHEMIST, TOOK A LOOK, AND FOUND LEVENE WAS WRONG!
IT WASN’T ATGCATGCATGC AT ALL!
IT WAS HIGHLY VARIABLE!
LIKE—— ATCGGCTATCGAATTCCG ETC.
CHARGAFF DISCOVERED THERE WAS AN EQUAL AMOUNT OF ATGC FOR HUMANS = 100%
FOR THE EUCALYPTUS PLANT ANOTHER EQUAL AMOUNT OF ATGC = 100%
HE DISCOVERED SAY 20% OF A = 20% OF T
30% OF G = 30% OF C = 100%
ANOTHER CREATURE COULD BE 18% A 18% T
32% G 32% C = 100%
NOW FITTING ALL THESE OBSERVATIONS TOGETHER—
PHYSICAL CHEMISTRY LOOKS AT ATOMS IN A 3 DIMENSION SPACE.
WATER MOLECULES H2O = ALL THE SAME, NO DIFFERENCE IN ANY WATER MOLECULES.
HUMANS ARE 70% WATER; NO COMPLICATED INSTRUCTIONS OF HUMAN STRUCTURE IN WATER.
DNA = MILLIONS OF ATOMS.
WAS THERE A SHAPE TO DNA?
SHINING X-RAYS THROUGH IT—
RAYS GO IN - GET BOUNCED AROUND BY ALL THE ATOMS - COME OUT AT THE OTHER END. PUT A PHOTO-GRAPHIC PLATE THERE, AND A PATTERN IS SHOWN ON HOW MUCH BOUNCING AROUND TAKES PLACE.
THE X-RAY PATTERNS WERE FOUND TO BE VERY REGULAR.
MAURICE WILKINS [1916 - 2004] AND ROSALIND FRANKLIN [1920 - 1958], WORKING AT KINGS COLLEGE, LONDON, IN THE EARLY 1950s.
THEY DID X-RAY ANALYST OF DNA, AND FOUND REGULARITY, LIKE A COIL OR POPULAR SLINKY COIL, CALLED HELIX.
JAMES WATSON [B. 1928] AND FRANCIS CRICK [1916 - 2004]
WORKING AT CAMBRIDGE UNIVERSITY, LOOKED AT ALL THIS.
MAYBE, JUST MAYBE DNA IS A DOUBLE HELIX —— TWO POLOMER—— SUGAR/PHOSPHATE ON THE OUTSIDE FOR THE BACK-BONE.
THEY TRIED TO PUT IT ALL TOGETHER.
THE ONLY WAY WAS A DOUBLE-HELIX.
ON THE OUTSIDE AND BEADS AT A T G C ON THE INSIDE, JUST FITTING TOGETHER LIKE A BASEBALL IN A GLOVE - FITTING BUT NOT TIGHTLY - NOT A BOND, FITTING WEAKLY BUT A FIT.
NO OTHER STRUCTURE WORKED BUT A DOUBLE-HELIX.
CRICK’S WIFE WAS AN ARTIST, SHE DREW A DOUBLE-HELIX.
THEY PUBLISHED A ONE PAGE ARTICLE TO PROVE THEIR POINT.
THIS MODEL WAS IMMEDIATELY ACCEPTED.
A BEAUTIFUL ELEGANT STRUCTURE; THEY WON THE NOBEL PRIZE.
FOUR REQUIREMENTS - DNA
1. INFORMATION STORAGE.
2. ACCURATE DUPLICATION
3. EXPRESSION AS PHENOTYPE
4. ABILITY TO CHANGE [MUTATE]
1. DNA INFORMATION
USING A T G C IN VARIOUS PATTERNS—— HUGE LANGUAGE!
BUT A AND T ARE ALWAYS TOGETHER, THEY FIT TOGETHER LIKE BASEBALL INTO GLOVE.
AND G AND C ARE ALWAYS TOGETHER, BASEBALL INTO GLOVE.
A AND T = ONE PAIR
G AND C = ONE PAIR
EXAMPLE:
469 BASE PAIRS OF DNA FOR HUMAN INSULIN.
THE GENE THAT GIVES US INSULIN IS 469 BASE PAIRS.
THE BEGINNING OF THIS GENE IS——
AGCCCTCCAGGACAGGCTGCAT………….
THE OTHER STRAND IS THERE BECAUSE WHERE YOU HAVE AN A YOU HAVE T. WHERE YOU HAVE A G YOU HAVE C.
SO WE HAVE, LOOKING AT THE BEADS ABOVE FOR INSULIN, WE HAVE——
A G C C C T C C A
T C G G G A G G T ETC.
IF WE KNOW THE ONE STRAND WE KNOW THE OTHER STRAND.
HUMANS HAVE OVER 3 BILLION BASE PAIRS OF DNA—— LOTS OF INFORMATION.
INFORMATION THAT MAKES YOU YOU—— HAIR COLOR, EYE COLOR, DIMPLE, SHAPE OF EYES, SHAPE OF NOSE, ETC.
2. DNA REPLICATION
WATSON AND CRICK SAID IT HAS NOT GONE UN-NOTICED OUR DOUBLE-HELIX IS GREAT FOR DUPLICATION.
LIKE A ZIPPER IT CAN UNWIND EASILY.
A LOOSE CONNECTION A AND T G AND C —— UNZIPPING.
THE OLD STRANDS ACT AS A TEMPLATE FOR THE NEW STRANDS.
STRAND AAAAA
WITH TTTTT
UNZIP
AAAAA
TTTTT
SOMETHING COMES INTO PLAY TO MAKE A NEW STRAND
AAAAA - OLD
TTTTT - NEW
TTTTT - OLD
AAAAA - NEW
THE SAME FOR G AND C
THIS WE CALL SEMI-CONSERVATISM REPLICATION—— IT HAS NOTHING TO DO WITH POLITICS.
YOU ARE CONSERVING THE OLD STRAND OF DNA.
YOU ARE ADDING OR REPLICATING [DUPLICATING] NEW STRANDS.
MOTHER AND FATHER = DNA [SPERM] DNA[EGG]
COMBINE = ONE CELL
CELL DIVIDES = REPLICATING
CELLS DIVIDE - MORE AND MORE = NEW PERSON.
IS IT POSSIBLE TO HAVE A CELL WITH PARENTS DNA SOMEWHERE IN ALL OUR CELLS?
MAYBE!
WE HAVE ABOUT 60 TRILLION CELLS IN THE HUMAN!
NOW WITH WHAT WE HAVE LEARNT SO FAR——
WHO INVENTED THIS DNA? IT IS A HUGE LANGUAGE AS WE HAVE SEEN. COULD THIS BASIC 4 LETTER LANGUAGE JUST HAVE INVENTED ITSELF? 469 BASE PAIRS TO TELL WHATEVER, TO MAKE INSULIN!
COULD RANDOM CHANCE OF THESE FOUR CHEMICALS FALLING TOGETHER IN 469 BASE PAIRS, JUST BY CHANCE THROUGH EVOLUTION, HAVE HAPPENED BY CHANCE?
DOES EVOLUTION HAVE A MIND, A BRAIN; DOES IT SPEAK TO ITSELF AND SAY, “OKAY YOU FOUR CHEMICALS EXPERIMENT AROUND UNTIL YOU FORM A LANGUAGE OF WHAT YOU HAVE TO TELL THIS OTHER THING/S TO FORM AND MAKE INSULIN".
HOW COULD EVOLUTION WITH NO BRAIN DECIDE THAT YOU HAVE TO GET 469 BASE PAIRS OF DNA FORMED TOGETHER TO HAVE THE LANGUAGE TO TELL THE NEXT WHATEVER OF EVOLUTION, TO START MAKING INSULIN FOR THE HUMAN BODY, WHICH WITHOUT YOU ARE GOING TO SERIOUSLY MESS UP THE HUMAN BODY WHICH WILL NOT SURVIVE.
AND WHEN YOU PUT THAT WITH ALL THE MANY MANY OTHER THINGS OF THE HUMAN BODY, THAT NEEDS TO BE PUT TOGETHER CORRECTLY……. I MEAN….. YOU DON’T HAVE HAIR GROWING OUT OF YOUR EYES, OR FROM YOUR FINGER NAILS. YOU DON’T HAVE TWO HEARTS ONE ON EACH SIDE OF YOUR CHEST.
IF EVOLUTION IS IN CHARGE YOU’D THINK IT COULD HAVE 100 OR 50 BASE PAIRS OF DNA TO MAKE INSULIN, AND NOT 469—— WHY NOT 470, WHY ON EARTH 469, AN ODD NUMBER TO SAY THE LEAST.
AND THIS IS JUST THE START OF THE PATHWAY FOR INSULIN TO BE MADE.
HOW DID EVOLUTION DECIDE ON DUPLICATING? DID EVOLUTION SAY TO ITSELF, “WELL WE WILL UN-ZIP OUR DNA STRAND?” BEFORE EVEN THAT, HOW DID EVOLUTION DECIDE IT WOULD BE A DOUBLE-HELIX? THEN EVEN BEFORE THAT HOW DID EVOLUTION DECIDE UPON 4 CHEMICALS FOR A and T G and C ? WHERE DID THEY COME FROM? HOW DID EVOLUTION DECIDE A WOULD COUPLE WITH T AND G WOULD COUPLE WITH C ? AFTER UN-ZIPPING HOW DID EVOLUTION FIGURE HOW TO MAKE A NEW STRAND THAT WOULD COUPLE WITH THE OLD STRAND? HOW DID EVOLUTION DECIDE A AND T TOGETHER AND G AND C TOGETHER WOULD BE THE BASE FROM WHICH A LANGUAGE WOULD COME TOGETHER; AND HOW DID EVOLUTION DECIDE THE A T G C WOULD NOT BOND BUT BE LOOSE YET CONNECTED?
THERE ARE SO MANY PARTS TO THE HUMAN BODY EACH WITH ITS CODE OF LANGUAGE, HOW COULD SLOW EVOLUTION, OR EVEN A QUICK MUTATION, EVER KEEP ALL OF THESE DNA LANGUAGE SEPARATE FROM EACH OTHER?
BACK TO INSULIN——
AS THESE 24 LECTURE ON GENETICS SHOW THERE ARE A NUMBER OF MAZING THINGS YOU MUST HAVE, FOR THE BASIC BLUEPRINT OF INSULIN TO COME INTO BEING; THE CORRECT LANGUAGE OF THE BLUEPRINT IS ONLY THE BEGINNING, YOU HAVE TO HAVE OTHER THINGS THAT PUTS THE LANGUAGE INTO THE PRACTICALITY OF LITERALLY MAKING ALL THAT IS INSIDE THE INSULIN, TO DO WHAT IS REQUIRED OF IT IN THE HUMAN BODY, FOR THAT BODY TO FUNCTION IN A NORMAL MANNER.
AND WHO DECIDED WE HAVE TO HAVE INSULIN IN THE FIRST PLACE?
DID EVOLUTION SIT DOWN AND SAY, “WELL NOW, FOR US TO MAKE A HUMAN PERSON, WE WILL DECIDE ONE PART OF THAT NORMAL LIVING PERSON WILL HAVE TO HAVE INSULIN, AND THIS IS HOW WE SHALL DO IT.”
WHEN YOU ADD UP ALL THE PARTS IN A NORMAL HUMAN PERSON, HOW ALL PARTS MUST FIT TOGETHER CORRECTLY TO MAKE A LIVING PERSON, AND TO THINK EVOLUTION, EVEN GIVEN MILLIONS OF YEARS COULD EVER DO SUCH A MIRACULOUS FEAT OF ENGINEERING, IS BEYOND ALL COMMON SENSE, BUT COMMON SENSE JUST AIN’T COMMON TODAY!
AND WHILE EVOLUTION WAS TRYING THIS AND TRYING THAT, AS IT STUMBLED ALONG OVER MILLIONS OF YEARS, TO GET THE HUMAN AS HE IS TODAY, WHY HAVE WE NOT FOUND ALL KINDS OF STRANGE AND FREAKISH “HUMANS” IN THE GROUND, AS EVOLUTION MESSED UP DOWN THROUGH TIME, TO COME UP WITH THE FINAL HUMAN BEING WE HAVE ON EARTH TODAY.
AS ONE SERIOUS JOKE GOES—— IF WE HUMANS DESCENDED FROM MONKEYS, WHY DO WE STILL HAVE MONKEYS?
AND I COULD ADD WHY HAVE WE NOT FOUND 1/2 MONKEY AND 1/2 MAN, OR ANY OTHER MIXED PERCENTAGE, SOMEWHERE IN THE GROUND?
SO WE ARE BACK TO SAYING WHO TOLD EVOLUTION THAT IT WOULD TAKE 469 BASE PAIRS OF DNA JUST TO MAKE INSULIN?
AS GOD’S WORD THE HOLY INSPIRED BIBLE SAYS, ONLY THE FOOL HAS SAID IN HIS HEART THERE IS NO GOD [PS. 14: 1].
GENETICS AND DNA
3. MUTATION
PASSED ON TO NEW GENERATION AS PERMANENT.
EXAMPLE——
ATCGGTTAACT —— CHANGED TO
ATCAGTTAACT
TAGTCAATTGA
ERRORS IN DNA DO HAPPEN - ONE IN A MILLION, BUT IT HAPPENS!
MOST ARE REPAIRED IN DNA
THERE IS A LITTLR SOMETHING MACHINE THAT GOES ALONG REPAIRING DNA!
AN ERROR WOULD BE A
G
SHOULD BE A
T
IF AN ERROR IS NOT CAUGHT AND CORRECTED IT IS PASSED ON TO THE NEXT GENERATION!
MANY PROBLEM PHYSICAL/MENTAL ARE FROM FAULTY DNA BASES = FAULTY GENES.
JUST ONE FAULTY GENE CAN HAVE OR RESULT IN A HUGE PHYSICAL/MENTAL—- NOT A NORMAL PERSON!
REPEAT—— ONE FAULTY GENE CAN HAVE HUGE PHYSICAL/MENTAL RESULTS IN THE BODY OF A PERSON.
A FEW FAULTY GENES CAN EQUAL VERY VERY SEVERE PHYSICAL/MENTAL PROBLEMS.
4. ABLE TO BE EXPRESSED—— EXPRESSION!
EXAMPLE:
SPIDER WEB——
A. IT’S ITS HOME
B. IT’S WHERE IT MATES - REPRODUCES
C. CAPTURES ITS FOOD
THE WEB HAS TO BE STRONG, STRECH, BUT NOT WABBLE OR GET OUT OF CONTROL.
THE SPIDER STRAND——
* THINNER THAN THE HUMAN HAIR
* STRONG - THEY ARE STRONGER THAN STEEL
* YET MORE FLEXIBLE THAN PLASTIC
SPIDER SILK IS MADE OF PROTEINS CALLED “SILK”—— THE SILK IN CLOTHES COMES FROM THE SILK WORM, DIFFERENT - A DIFFERENT SUBSTANCE - A DIFFERENT MOLECULE.
SILK FROM THE SPIDER IS LARGER MOLECULE AND CONTAINS ALL KINDS OF CHEMICALS IN A CERTAIN ORDER.
THE SPIDER MANUFACTURES IT SOME HOW, AND IT COMES OUT OF ITS BACK-END.
WE ARE STILL RESEARCHING IT ALL [IT MAY WELL BE ALL KNOWN BY NOW, AS THESE DVDs ARE FROM SOME YEARS BACK - Keith Hunt]
NOW TO PROTEINS
THEY ARE POLOMERS = THE CHAIN - MOLOMERS THE BEADS.
PROTEINS = 20 AMENO-ACIDS [THEY ALL HAVE NAMES]
PROTEINS HAVE THEIR OWN SET ORDER, SO VERY LARGE.
PROTEIN STRANDS STRAND 10 - 1,000 AMINO-ACID BUILDING BLOCKS.
THE SPIDER SILK HAS CERTAIN AMINO-ACIDS IN A CERTAIN ORDER—— IT THEN GIVES THE SILK ITS STRUCTURE AND PURPOSE—- WHAT IT IS FOR WHAT IT WILL DO.
SO SPIDER GENES = SPIDER SILK
DNA IN THE GENE WITH THE PROTEIN = SPIDER SILK.
PROTEIN MOLECULE = CHAIN OF AMINO-ACIDS.
R
H——-N————C C———OH
H H O
Amino Group Acid Group
H2N CO2H
HUMANS LACK THE GENETIC CAPACITY TO MAKE 8 OF THE 20 AMINO ACIDS.
BACTERIA CAN DO IT - PLANTS CAN DO IT.
THEY CAN REARRANGE THE CARBONS, OXYGENS, SULPHUR, PHOSPHORUS, HYDROGEN, ETC. - REARRANGE AND MAKE ALL 20 AMINO ACIDS.
WE HAVE TO GET 8 AMINO ACIDS IN OUR DIET.
VERY IMPORTANT FOR OUR DIET AND FOR AGRICULTURE.
[IF WE DO NOT GET CITRIC ACID [Citric acid is a weak organic acid that has the chemical formula C6H8O7. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in the metabolism of all aerobic organisms] IN OUR DIET, WE GET SCURVY, A DEFICIENCY IN VITAMIN C.
MANY SAILORS DIED OF SCURVY WHEN BRITAIN AND NATIONS OF EUROPE WERE FIRST MOVING ACROSS THE ATLANTIC. THEY FINALLY DISCOVERED EATING FRUIT WAS THE ANSWER. THE ENGLISH WERE CALLED “LIMIES” BECAUSE THEY CARRIED TUBS OF LIMES FOR THE SAILORS TO SUCK ON - Keith Hunt]
AMINO ACID FOLDING
THE WONDER OF GENES, DNA,
FROM THE 4 DVD SET I HAVE - 24 HALF HOUR LECTURES BY A Ph.D. FELLOW, PRODUCED AND SOLD BY THE TEACHING COMPANY.
Quote
IN THE LAST TWO LECTURES I’VE DESCRIBED HOW GENES COMPOSED OF DNA, ARE EXPRESSED OUTWARDLY AS THE PHENA-TYPE, WHICH I DEFINED AS PROTEINS.
PROTEIN HAS AMINO-ACIDS THAT ALLOW PROTEIN TO FOLD AND HAVE A FUNCTION.
IN THIS LECTURE I’D LIKE TO DESCRIBE HOW THIS HAPPENS - HOW THE INFORMATION GETS TRANSFERRED FROM DNA TO PROTEIN.
A POISON CALLED “RICIN” IS EXTRACTED FROM THE CASTOR BEAN PLANT.
AS A KID MY MOTHER WOULD GIVE ME CASTOR-OIL - IT WAS THE VILEST THING I’D EVER TASTED.
RICIN WAS USED BY THE IRAQIS IN THEIR WAR WITH IRAN.
IN 2002 SOME RICIN WAS FOUND IN CAVES IN AFGHANISTAN BY ALCADA.
IN 2004 TRACES WERE FOUND IN D.C. BUILDING - THE PLACE WAS CLOSED DOWN.
ONE TENTH OF A THOUSAND OF AN OUNCE CAN KILL A PERSON.
HOW? IT WORKS BY INHIBITING GENE EXPRESSION.
THE CASTOR-BEAN PLANT MAKES RICIN AS A STORAGE IN ITS SEEDS.
IT INHIBITS THE PROTEIN TO NOT BE EXPRESSED.
RICIN EFFECTS THE RIBOSOME - THE PLACE WHERE PROTEIN WILL BE MADE, WHICH IS OUTSIDE THE CENTER WHERE THE DNA IS.
NO PROTEIN, NO EXPRESSION - THE CELL DIES - PEOPLE DIE.
TRANSLATING INFORMATION IN THE GENE [DNA] AS ITS EXPRESSION [PROTEIN]
1. PROBLEM OF TRANSLATION
2. INFORMATION SIGNALS FOR PROTEIN
3. THE GENETIC CODE
WE HAVE SEEN HOW GENES ARE EXPRESSED IN PROTEIN - THIS BRINGS A BIG CHEMICAL PROBLEM, BECAUSE GENES [DNA] ARE REALLY DIFFERENT THAN PROTEINS. THE BUILDING BLOCKS OF DNA ARE CHEMICALS TOTALLY DIFFERENT THAN THEIR EXPRESSION AS PROTEINS.
IT’S LIKE SAYING ENGLISH IS DIFFERENT THAN HEBREW - THE LETTERS LOOK DIFFERENT, AND EVEN READING IS LEFT TO RIGHT IN ENGLISH, AND RIGHT TO LEFT IN HEBREW.
PROTEINS ARE COMPOSED OF AMINO-ACIDS AND ARE PRETTY REGULAR IN THEIR LINEAR STRUCTURE.
DNA IS A DOUBLE HELIX - COMPOSED OF NUCLEAR-TIES; NITROGEN, SUGAR, PHOSPHATE, AS A BACK-BONE, WITH THESE FOUR CHEMICALS—— ADENINE [A], THYMINE [T], GUANINE [G], CYTOSINE [C].
THERE ARE 20 AMINO ACIDS IN PROTEIN NOT JUST 4.
THE MOLECULE STRUCTURES ARE DIFFERENT - NOT AT ALL LOOKING ALIKE.
PROTEINS FOLD IN A ZIG-ZAG STRUCTURE, WHEN IN WATER - BEADS ON A CHAIN — /\/\/\/\/\/\/\
DIFFERENT PLACES
DNA AND PROTEINS ARE LOCATED IN DIFFERENT PLACES IN THE CELL.
DNA IS IN THE NUCLEUS OF THE CELL.
PROTEINS ALL OVER THE CELL, AND ALSO IN THE NUCLEUS, EVERYWHERE, AS VITAL FUNCTIONS AS STRUCTURAL ELEMENTS AND ENZYMES, PHENOTYPIC EXPRESSIONS OF GENES.
DNA IS LINEAR SEQUENCE
PROTEINS ARE 3-DIMENSION SEQUENCE
PROTEIN IS MADE IN A DIFFERENT LOCATION FROM DNA.
PROTEIN IS MADE AT THE RIBOSOME - A SMALL PART OUTSIDE OF THE NUCLEUS.
WE KNOW THIS BECAUSE WE CAN TAKE A CELL AND FEED IT AMINO-ACIDS THAT ARE LABELED IN SOME WAY, SAY A MINO-ACID WITH RED DYE. IF YOU CATCH A PROTEIN JUST BEING MADE, YOU’LL CATCH IT AT THE RIBOSOME, FAR AWAY FROM DNA.
SO WE HAVE A GEOGRAPHICAL AND CHEMICAL PROBLEM!
INFORMATION SIGNALS ARE VERY IMPORTANT IN PROTEIN SYNTHESIS.
SO DNA HAS TO SEND SOME INFORMATION AND SIGNALS FOR PROTEIN SYNTHESIS; DNA MUST SEND THESE OUT TO THE RIBOSOME.
TWO WAYS TO LOOK AT IT——
1. GENE/DNA GOES OUT OF THE NUCLEUS AND SAYS, “I HAVE INFORMATION TO MAKE THIS PROTEIN; DO IT NOW.”
2. THE DNA SAYS, “WELL I’VE GOT A THOUSAND GENES PER CHROMOSOME AND 23 CHROMOSOMES. AND IT WOULD NOT MAKE SENSE FOR A 1,000 GENES TO BE MADE AT ONCE, TO BE TRANSLATED INTO PROTEIN. SO IF WE’RE ONLY GOING TO EXPRESS OR TRANSLATE A COUPLE OF THESE GENES, WHY NOT JUST SEND A COPY OF THE DNA, AND THE ORIGINAL DNA CAN STAY IN THE NUCLEUS.”
THINK OF IT THIS WAY——
A HOUSE BUILDING FIRM, IT HAS ALL THE BLUE-PRINTS OF ALL THE HOUSES IT IS WORKING ON TO BUILD, AT ITS HEAD-OFFICE BUILDING. THE FIRM WILL SEND A COPY OF THE BLUE-PRINT OUT TO ALL THE HOUSES IT IS BUILDING; THE ORIGINAL BLUE-PRINT WILL STAY AT THE FIRM’S HEAD-OFFICE.
THINK OF DNA EXPRESSION IN THE SAME WAY.
A COPY OF THE DNA IS SENT OUT TO THE RIBOSOME.
NOW THE EXACT CHEMICAL NATURE OF THIS COPY IS NOT QUITE THE SAME AS THE ORIGINAL DNA. A DIFFERENT MOLECULE— CALLED— RNA.
RNA—— RIBONUCLEIC ACID
DNA——- DEOXYRIBONUCLEIC ACID
THE SUGAR IS DIFFERENT ALSO
RNA SUGAR—— RIBOS
DNA SUGAR—— DEOXIRIBOS
RNA IS A SINGLE STRAND NOT A DOUBLE STRAND AS IS DNA.
VERY IMPORTANT
SINGLE STRAND EXPOSES THE BEADS HANGING DOWN FROM ITS BACK-BONE.
DNA - DOUBLE HELIX BEADS ARE NOT EXPOSED - BACKBONE IS ON EITHER SIDE, BEADS LOOSELY FITTING TOGETHER——
A WITH T
G WITH C
RNA IS ACTING AS A MESSENGER FROM DNA, SO WE CALL IT messengerRNA OR mRNA.
THE LANGUAGE IS STILL IN NUCLEAR TIES - IN BASES.
THE ENZIME THAT CATALYSES THE PRODUCTION OF RNA FROM DNA HAS A NAME—— RNA POLYMERASE LIKE DNA POLYMERASE. AND IT MAKES A BASE PAIRED COPY FROM DNA.
WHAT DO I MEAN BY THAT?
CONSIDER THE BASE PAIRS IN DNA—— A + T G + C
THEY FIT INTO EACH OTHER——
AAAAAA
TTTTTT
LET’S SAY THE INFORMATION CONTENT IS IN THAT FIRST STRAND—— AAAAAA
RNA DNA
A T A
A T A
A T A
A T A
A T A
A T A
THAT MOLECULE COPY [RNA] GOES OUT TO THE RIBOSOME.
DNA IS DOUBLE STRANDED
WHY?
DOUBLE STRANDED ALLOWS FOR ITS DUPLICATION.
THE NEW STRANDS HAVE A COMPLIMENT FROM THE OLD STRAND.
IF ONE STRAND ONLY YOU COULD NOT UN-ZIP AND YOU COULD NOT GET A COMPLIMENT STRAND IF ONLY AAAAAA
REPLICATING AAAAAA
GIVES YOU AAAAAA
YOU HAVE NO TTTTTT
IT IS NICE THAT DNA IS DOUBLE STRANDED!
SO WE HAVE OUR AAAAAA GOING OUT OF THE NUCLEUS TO THE RIBOSOME.
HOW DOES IT GET THERE?
WELL THERE’S LOTS OF MECHANICS GOING ON HERE IN THE NUCLEUS.
LITTLE HOLES AND ……
PEOPLE HAVE STUDIED IT; ALL COMPLEX MECHANICS; IT’S NOT FOR THIS STUDY.
BUT THERE IS AN IMPORTANT FACT HERE WE HAVE TO ADDRESS.
EACH CHROMOSOME PIECE OF THE DNA, OF THE 23 CHROMOSOME PAIRS IN A HUMAN GENENO HAS OVER 100 MILLION BASE PAIRS!
WE ONLY EXPRESS SMALL PARTS OF A GENE AT GIVEN TIMES - WE DO NOT EXPRESS ALL AT ALL TIMES.
EXAMPLE:
YOU DO NOT MAKE HEMOGLOBIN IN YOUR HAIR; YOU DO NOT MAKE HAIR IN YOUR BONE MARROW.
WE DO HAVE THE GENES FOR MAKING THEM.
SO A LONG CHROMOSOME MIGHT HAVE BOTH OF THEM.
WHAT IS GOING TO MAKE OR EXPRESS ONE BUGT NOT THE OTHER?
THERE HAS TO BE AN INFORMATION SIGNAL AND THAT SIGNAL HAS TO BE IN THE DNA ITSELF.
End Quote
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ARE YOU FOLLOWING IT ALL; PRETTY COMPLICATED STUFF IN US AND HOW WE ARE MADE.
WHY HAVE DIFFERENT DEPARTMENTS IN THE GENE CELL? IT MEANS EVOLUTION HAD TO SAY TO ITSELF, “WELL AS I’M PUTTING THINGS TOGETHER TO EXPRESS ALL THIS INFORMATION, I’LL PUT IT IN DIFFERENT SECTIONS, AND WITH THAT I’VE GOT TO INVENT A CARRIER TO GO FROM A TO B, SOMETHING MECHANICAL.
THEN EVOLUTION WENT FROM 4 CHEMICALS IN DNA LANGUAGE TO PUTTING IN 20 AMINO-ACIDS TO MOVE ON TO EXPRESSING THE INFORMATION IN DNA.
THEN IT HAD TO FIGURE WHAT PARTS TO EXPRESS, SO HAIR DOES NOT GROW OUT OF YOUR EYE-BALL, OR BONE-MARROW.
ARE YOU SEEING THE MARVEL, THE WONDER, OF MAKING A LIVING PERSON, AND ALSO A LIVING HORSE, AS OPPOSED TO A COW, OR A DUCK, OR AN EAGLE, OR A DOLPHIN?
ALL LIFE FORMS HAVE A BASIC FOUNDATION—— GENES AND DNA THAT HAS TO BE EXPRESSED, AND EXPRESSED RIGHTLY SO A HORSE IS A HORSE, A COW IS A COW, AND NOT A MESS-UP THAT ENDS UP AS SOME FREAKISH MIX OF THE TWO.
WHY 20 AMENO-ACIDS INVOLVED? WHY DO HUMANS ONLY PRODUCE 12 OF THEM, AND WE HAVE TO GET THE REST FROM OUT DIET?
DID EVOLUTION SAY TO ITSELF, “I WILL KEEP THE BLUEPRINT OF THE DNA WE WILL EXPRESS, WHERE IT IS AND MAKE A COPY TO SEND OUT TO THE EXPRESSION DEPARTMENT.” I MEAN HOW DOES SOMETHING LIKE THAT HAPPEN WHEN WE KNOW EVOLUTION DOES NOT HAVE A MIND TO THINK WITH AND REASON AND PLAN?
HOW DID AND DOES EVOLUTION KNOW HOW TO EXPRESS JUST PARTS OF DNA, PART OF THE GENE, THE PARTS THAT WILL MAKE A HUMAN, OR A HORSE, OR COW, OR AN EAGLE, OR A DOLPHIN AND SO FORTH, IN THE RIGHT PLACE AT THE RIGHT TIME, SO HAIR DOES NOT GROW OUT OF YOUR EYEBALL, A FINGER DOES NOT GROW OUT OF YOUR NOSE ETC.
ONLY A CREATOR GOD COULD DO ALL THIS, AND THEN ALSO SAY “AFTER ITS KIND” SHALL IT EXIST; YOU CAN NOT CROSS A HORSE WITH A COW, AND ETC. AND ETC.
THE WONDERS OF NATURE ARE INDEED MIND-BLOWING!
THE WONDERS OF NATURE PROVE THEIR IS A GOD WHO CAN CREATE ALL THERE IS IN THE UNIVERSE.
TRULY AS THE HOLY BIBLE SAYS, ONLY THE FOOL HAS SAID IN HIS HEART THERE IS NO GOD.
THE WONDER OF GENETICS AND DNA
WE CONTINUE WITH THE LECTURES FROM A Ph.D. MAN, FROM THE TEACHING COMPANY, ON THE MIND-BENDING SUBJECT OF “GENETICS AND DNA.”
This part gets into some nitty-gritty of it all, somewhat harder to follow— but very revealing!
Quote:
SO A GENE IS NOT JUST A SEQUENCE OF INFORMATION, WHICH DETERMINES WHAT PROTEIN IS GOING TO BE MADE, AND THE ORDER OF AMINO ACIDS, AND THE ORDER OF AMINO ACIDS IN THAT PROTEIN.
A GENE HAS TO HAVE A SEQUENCE ADJACENT TO IT, THAT SAYS, FOR EXAMPLE, “TURN ME ON IN THE RED BLOOD CELL AND NOT IN THE HAIR.”
THAT SEQUENCE IS A GROUP OF NUCLEOTIDES THAT’S DIFFERENT FROM THE HAIR GENE THAN THE HEMOGLOBIN GENE.
AND THAT SEQUENCE OF NUCLEOTIDES IS CALLED A PROMOTER.
THIS IS A SIGNAL SEQUENCE FOR GENE EXPRESSION.
A PROMOTER IS A SEQUENCE OF NUCLEOTIDES THAT IS RECOGNIZED BY PROTEINS.
WHAT DO I MEAN BY THAT?
I’VE GIVEN YOU THE IMPRESSION THAT IN TERMS OF INFORMATION THAT, INFORMATION CONTENT DNA IS PRETTY IMPORTANT - THE A T G C LANGUAGE IS GREAT.
NOW I’M TELLING YOU THAT A T G C AND SEQUENCE OF NUCLEOTIDES ALSO IS 3 DIMENSION INFORMATION THAT PROTEINS FOLD ON A 3 DIMENSION NATURE.
SO IF WE HAVE A PROTEIN CALLED RNA POLYMER RAYS, THOSE WILL LAND ON DNA ONLY AT THAT PROMOTER REGION.
THAT’S NOT HELPING US AT ALL, FOR RNA POLYMER RAYS WILL LAND AT THE PROMOTER FOR HAIR IN MY BONE MARROW. BONE MARROW WILL START MAKING HAIR, SO LANDING JUST ANYWHERE WILL PRODUCE BAD RESULTS.
PROMOTERS ATTRACT OTHER PROTEINS—— IT IS CALLED A COMPLEX.
MAYBE DUE TO THE PEOPLE WHO STUDY THIS THING—— PSYCHOLOGICALLY, BUT IT’S A COMPLEX OF PROTEINS THAT LAND THERE.
EXAMPLE:
HEMOGLOBIN IS MADE IN RED BLOOD CELLS, THERE’S A HORMONE THAT STIMULATES THIS. THAT’S GOING TO BE THE BIG DIFFERENCE!
THE HORMONES ENTER THE RED BLOOD CELLS IN THE BONE MARROW, AND THE HORMONE BINDS TO THE MOLECULES IN THE BONE MARROW, AND TOGETHER THEY GO INTO THE NUCLEUS AND BIND TO THE PROMOTER. AND WITH THE RNA POLYMER RAYS THEY SAY “MAKE THE COPY HERE.”
THAT’S REALLY IMPORTANT BECAUSE IT SAYS THE PROMOTER IS THAT WHICH DIFFERENTIATES AND STIMULATES ONE CELL AND GENE FROM ANOTHER.
THIS PROCESS OF MAKING A RNA COPY GENE IS DUE TO THE PROMOTER AND THE SPECIFIC NATURE OF THE PROMOTER—— IS DNA TRANSCRIPTION.
D N A
R N A IS THE COPY BY THE PROMOTER.
NEXT STAGE IS DNA TRANSLATION
NOW WE HAVE AN RNA COPY AT THE RIBOSOME AND WE’RE GOING TO TRANSLATE THAT INTO AMINO ACIDS AND PROTEINS.
THIS IS DONE BY BRINGING THE AMINO ACIDS TO THE RIBOSOME.
AND HOW IS THIS GOING TO BE ACCOMPLISHED?
BY ANOTHER TYPE OF RNA CALLED tRNA—— TRANSFER-RNA.
tRNA GRABS THE AMINO ACIDS THERE IN THE CELL, BRINGING IT TO THE RIBOSOME AND THE TRANSFER RNA MADE UP OF NUCLEOTIDES, BEING OPPOSITE TO tRNA.
SO mRNA HAS SAY A A A
transferRNA HAS THE OPPOSITE NUCLEOTIDES AND WILL BIND TO IT.
THIS LANGUAGE IS CALLED GENETIC CODE— CODE WORDS WITH 3 BASES EACH.
LET US SAY THE LANGUAGE WAS ONLY ONE BASE.
mRNA - EVERY TIME THERE WAS AN “A” YOU WOULD BRING IN AMINO ACID #1.
4 DIFFERENT NUCLEOTIDES = 4 DIFFERENT AMINO ACIDS.
THAT’S NOT GOING TO WORK! YOU HAVE 20 AMINO ACIDS, YOU NEED 20 DIFFERENT WORDS IN THE
mRNA [messengerRN] TO BRING 20 AMINO ACIDS.
OKAY THERE ARE 4 BASS, LET’S MAKE 2 LETTERS,
A A GA GC - 16 POSSIBILITIES; NO THAT’S NOT GOING TO WORK EITHER.
WE NEED AT LEAST 20 DIFFERENT WORDS.
AND WE HAVE 20 IF WE HAVE 64.
SO IF THERE ARE 4 X 4 X 4 OR 3 NUCLEOTIDES IN THE CODE WORD IN mRNA, WE CAN ESSENTIALLY GET THE LANGUAGE WE NEED.
HOW THE CODE CAME TO US
THE CODE WAS DISCOVERED AND GIVEN TO US IN 1961 BY A FELLOW NAMED MARSHALL W. NIRENBERG [B. 1927].
HE TOOK A TEST TUBE AND ADDED EVERYTHING YOU NEED TO MAKE PROTEINS, EXCEPT mRNA, AND WHEN HE PUT IN mRNA JUST CONTAINING UUUUUUUUU IN mRNA WHICH IS EQUIVALENT TTTTTTTTT - A DIFFERENT NUCLEOTIDE——
HE ASKED “WHICH AMINO ACID WILL BE PUT INTO THE PROTEIN?”
AND IT TURNED OUT TO BE THE AMINO ACID PHENYLALANINE.
NEXT HE PUT IN AAAAAAAAA AND HE GOT LYSINE.
THEN HE TRIDE CCCCCCCCC
AND HE GOT THE AMINO ACID PROLINE.
AND THIS WAY HE DECIPHERED THE CODE, WITH THESE ARTIFICIAL TEST TUBE WITH mRNA.
NIRENBERG WAS YOUNG, QUIET, NOT AT ALL PUSHY; HE WAS AT THE 1961 INTERNATIONAL CHEMISTRY IN MOSCOW. HE PRESENTED HIS EXPERIMENT TO AN AUDIENCE OF LESS THAN 10 PEOPLE. NO ONE EVER HEARD OF HIM.
IN THE AUDIENCE WAS CRICK OF WATSON AND CRICK FAME.
CRICK HAD SEEN THE TITLE OF THE LECTURE AND THOUGHT MAYBE THIS FELLOW HAS CRACKED OPEN THE GENETIC CODE.
CRICK SAID TO HIM, “WOULD YOU LIKE TO GIVE YOUR TALK AGAIN TOMORROW MORNING?” IT WAS THE LAST DAY OF THE CONFERENCE.
“WELL, I WAS GOING TO LEAVE, BUT …. OKAY I’LL GIVE IT AGAIN.”
2,000 TURNED UP TO HEAR HIM; THEY GAVE HIM A STANDING OVATION.
ABOUT 2 YEARS LATER HE WON THE NOBEL PRIZE!
THERE ARE CODE WORDS FOR 20 AMINO ACIDS.
HERE’S A CHART OF GENETIC CODE ……
DNA MAKES THE mDNA WHICH HAS THE CODE WORD, WHICH DETERMINES THE ORDER OF THE AMINO ACIDS, AND THE CODE IS IN THE mRNA.
THE CODE IS VIRTUALLY UNIVERSAL FOR ALL LIFE ON EARTH.
WE USE THE SAME GENETIC CODE AS COCONUTS, AND AS BACTERIA—— WE HAVE A COMMON LANGUAGE.
THIS IMPLIES WE ARE ALL RELATED IN SOME WAY; WE CALL IT DESCENT WITH MODIFICATION.
HUMANS ARE ALL ALIKE WITH GENETIC MODIFICATION—— LOOK AROUND, WE ARE ALL DIFFERENT IN CERTAIN WAYS, BUT WE ALL HAVE THE SAME GENETICS.
IT TAKES ABOUT ONE MINUTE FOR A CELL TO MAKE A PROTEIN WITH 500 AMINO ACIDS—— THINGS ARE MOVING FAST DOWN THERE.
GENETIC CODING EXPLAINS THE PHENOMENON OF MUTATION.
CONSIDER THE DISEASE PHENYLKETONURIA [PKU].
IT IS GENETICALLY INHERITED— A GENE CODES FOR A DEFECTIVE ENZIME— MENTAL RETARDATION IS THE RESULT.
MUTATION IN PKU
NORMAL PKU
Length of Protein 451 Amino Acids 451 Amino Acids
DNA at codon 408 xxxCGGxxx xxxTGGxxx
xxxGCCxxx xxxACCxxx
mRNA at codon 408 CGG UGG
Amino Acid at position 408 Arginine Trytophan
Active Enzyme Yes No
ONE ABNORMAL AMINO ACID OUT OF 451 CAUSES THE PROTEIN TO FOLD IN A CERTAIN WAY……
ONE BASE PAIR CHANGE C TO A T OUT OF 3 BILLION IN THE GENENOM CAUSES ALL THE CLINICAL CHARACTERISTICS OF THIS DISEASE.
GENETICAL MUTATION IS——
A CHANGE IN BASE[S] IN DNA
C TO A T etc.
GENETIC CAPACITY—— THE PRESENCE OF DNA SEQUENCES THAT CODE FOR PROTEINS WITH SPECIFIC FUNCTIONS.
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WELL DONE IF YOU WERE ABLE TO FOLLOW ALL THAT.
THE HUMAN BODY IS INDEED WONDERFULLY MADE.
THIS MUST GO WITH THAT; THAT MUST GO WITH THIS; TWO TOGETHER DO THIS IN THE RIGHT PLACE TO DO IT; ALL THE A T G C MUST BE IN THE RIGHT ORDER; THE AMINO AIDS MUST LINE UP CORRECTLY.
THERE IS INFORMATION STORAGE DNA; THERE IS UN-ZIPPING AND REPLICATING; THERE IS COPYING; THERE IS THE MOVING OUT OF THE CELL INTO THE RIBOSOME.
THERE IS ALL THIS VERY INTRICATE STUFF GOING ON IN CELLS, PROTEIN, AMINO ACIDS, ENZYMES, THIS JOINING WITH THAT.
WE HAVE LITTLE MACHINES RUNNING UP AND DOWN OUR DNA TO CORRECT MISTAKES.
IN ALL WE HAVE SEEN IN JUST THESE 4 STUDIES, SHOULD BE ENOUGH TO BLOW OUR MINDS; IT IS WONDER UPON WONDER.
ALL THIS SHOULD PROVE THAT AN INTELLIGENT MIND WAS BEHIND IT ALL; IT SHOULD PROVE A BEING WE CALL “GOD” DOES EXIST.
SOMETHING THAT IS SO COMPLEX AS THE HUMAN BODY, AND HOW IT MUST ALL FIT CORRECTLY TOGETHER, TO PRODUCE WHAT WE CALL “NORMAL” FUNCTION; YET WITH THAT “NORMAL” IS THE ABILITY TO PRODUCE VARIOUS TALENTS, GIFTS AND ABILITIES, ALL THE WAY UP TO WHAT WE TERM “GENIUS”—— ALL THIS SHOULD HUMBLE US TO THE ACKNOWLEDGING THERE IS A GOD, WHO NOT ONLY MADE ALL THINGS ON THIS BLUE PLANET CALLED EARTH, BUT ALSO MADE AND SUSTAINS THE WHOLE UNIVERSE WITH ITS BILLIONS OF GALAXIES, FLYING APART FROM EACH OTHER AT AN EVER FASTER SPEED.
LIFE CAN ONLY COME FROM LIFE!
YOU CAN NOT TAKE A SLIVER OF ROCK OR WOOD AND MAKE IT COME TO LIFE.
LIFE COMES ONLY FROM LIFE.
ALL LIFE IS RELATED; YES GOD SAID TO MAN, FROM THE GROUND YOU ARE TAKEN AND TO THE GROUND YOU SHALL GO.
SO WE HAVE LIFE THAT PRODUCES AFTER ITS KIND; A HORSE CAN NEVER BECOME AN EAGLE; A LION CAN NEVER BECOME A RABBIT; A SPIDER CAN NEVER BECOME A DOLPHIN AND ETC.
BUT WHAT MAKES MANKIND DIFFERENT FROM ALL OTHER LIFE FORMS?
ANIMALS SMALL AND HUGE HAVE “BRAINS” - WE AS HUMAN BEINGS HAVE A BRAIN. BUT ONLY THE HUMAN CAN PRODUCE ENCYCLOPEDIAS, AND SPACESHIPS, AND THE COMPUTER AND SMART PHONES. THERE IS SOMETHING IN MANKIND THAT MAKES US DIFFERENT FROM ALL THINGS ON THIS EARTH. THE BIBLE CALLS IT “THE SPIRIT IN MAN.”
I HAVE A FULL DETAILED STUDY ON THIS WEBSITE CALLED “THE SPIRIT IN MAN.”
THEN YOU NEED ALSO TO STUDY MY STUDY CALLED “A CHRISTIAN’S DESTINY” AND LEARN THE WONDERFUL MIND-BLOWING REASON WHY THE ETERNAL GOD MADE MANKIND.
GENETICS —— GENOMES
Ph.D FELLOW FROM THE TEACHING COMPANY; 4 DVDs I HAVE— 24 HALF HOUR LECTURES, PUBLISHED IN 2007.
Quote
THE ENTIRE NUCLEOTIDES IN THE GENOME—— ENTIRE COMPLIMENT OF GENES THAT MAKE UP AN ORGANISM.
MY STORY BEGINS IN THE HISTORY OF GENOME SEQUENCING, THE EARLY 1900s WHEN GENETIC MUTATION WERE FIRST STUDIED, IN THE MODEL ORGANISM OF THE FRUIT FLY.
SCIENTISTS FOUND THERE WERE A NUMBER OF THINGS THAT WOULD INCREASE MUTATIONS.
MUTATION CAN HAPPEN WHEN DNA DUPLICATES AND AN ERROR HAPPENS.
SO GENETIC MUTION—— A CHANGE IN DNA BASES.
PEOPLE WORKING IN URANIUM MINES GOT CANCER— URANIUM AFFECTING GENES.
PEOPLE WORKING ON WATCHES THAT GLOW IN THE DARK - PAINTING WITH RADIUM; THEY USED SMALL BRUSHES THEY DABBED THE HAIRS ON THIER TONGUE TO TO KEEP HAIRS STICKING TOGETHER; THEY GOT ORAL CANCER.
BY 1930 RADIATION WAS STUDIED—— THE MORE RADIATION THE MORE DAMAGE TO GENES.
AT THE END OF WW2, TWO ATOMIC BOMBS FROM THE USA, EXPLODES ON THE JAPAN CITIES OF NAGASAKI AND HIROSHIMA. GREAT MANY EXPOSED TO RADIATION FROM THE FALL-OUT.
THESE PEOPLE HAVE BEEN STUDIED FOR YEARS - THE STUDY OF SOMATIC CELLS, WHICH ARE ALL CELLS BUT THE SEX CELLS. THE DAMAGE FOR MANY LED TO CANCER.
THE NEXT GENERATION WAS STUDIED FOR ABNORMALITIES.
BY THE 1970s WE HAD THE KNOWLEDGE OF DNA SEQUENCING; WE CAN SEQUENCE 800 BASE PAIRS AT A TIME.
MACHINES DO IT NOW.
SCIENTISTS INFERRED DAMAGE BY PHENO TYPE - ALL THESE JAPANESE WERE LOOKED AT THROUGH PHENO TYPE.
NOW WITH SEQUENCING WE COULD LOOK AT DNA RIGHT UP FRONT.
WE CAN SEE NORMAL STANDS OF DNA OF THE DOUBLE HELIX DNA—— A WITH T, G WITH C ETC.
WE CAN SEE DAMAGED DNA DOUBLE HELIX STAND SO EVIDENTLY AT TIMES, LIKE BLACK FROM WHITE.
RENATO DULBECCO [B. 1914 AND STILL ALIVE WHEN THESE DVDs WERE MADE] WON THE NOBEL PRIZE FOR STUDYING CANCER VIRUSES.
HE SUGGESTED DOCUMENTING ALL DNA— ALL A MAMOTH UNDERTAKING, BUT WE COULD THEN COMPARE NORMAL TO DAMAGED DNA.
THE HUMAN GENOME PROJECT—— USA FIRST TO START DOING IT— THE USA DEPARTMENT OF ENERGY.
SINCE THEN IT’S BEEN FARMED OUT TO OTHER ORGANIZATIONS.
THE HUMAN GENOME—— IN TWO WAYS
1. HUGE CHALLENGE - IN TWO WAYS.
CHROMOSOMES ARE EXTREMELY LONG. ON THE AVERAGE 100 MILLION BASE PAIRS OF DNA.
MACHINES COULD HANDLE 800 BASE PAIRS AT A TIME.
SO WE CUT THE 100 MILLION BASE PAIRS INTO 800 BASE PAIR FRAGMENTS. HOW MANY IS THAT? YOUR ASSIGNMENT—— IT’S A LOT!
THEN YOU HAVE TO FIT THEM BACK TOGETHER. O YA, HOW DO YOU KNOW WHICH GOES WITH WHICH?
WE’RE CUTTING RANDOMLY, SO FITTING TOGETHER…. WELL HOW?
RESTRICTION ENZYMES WILL CUT AT CERTAIN PLACES. OR WE CAN CUT IT, BUT AT RANDOM.
IT’S LIKE TAKING THE PRINTED GUIDE FOR THIS COURSE, CUTTING OUT EACH WORD, THROW THEM UP IN THE AIR, THEY LAND ON THE FLOOR; THEN WE MUST TRY TO PUT TOGETHER AND MAKING THE SENTENCES I’VE WRITTEN—— GOOD LUCK, VERY HARD TO DO.
WE NEED SOME SIGN-POSTS!
1— IT WAS CALLED HIERARCHICAL SEQUENCING.
2— SHORT GUN SEQUENCING.
FIRST ONE:
GOVERNMENT SPONSORED, ACTUALLY MANY GOVERNMENTS NOT JUST THE USA. THOUSANDS OF SCIENTISTS LED BY FRANCIS S. COLLINS [B. 1950].
WHAT THEY DECIDED TO DO WAS TO IDENTIFY SHORT SEQUENCE MARKING ALL THE WAY DOWN THE CHROMOSOME.
OKAY, THE WORDS ON THE FLOOR— WE NEED A SIGN POST. WELL IN LECTURE TWO THE WORD “MENDAL” CAN BE FOUND.
SO SHORT SEQUENCE, WITH SOME SIGN POSTS. IT TOOK 10 YEARS AND THOUSANDS OF SIGNS PUT ALONG THE CHROMOSOME.
THEN CUT INTO 800 BASE PAIRS— TOOK ALL IN— 12-15 YEARS DEPENDING HOW YOU DEFINE IT.
SECOND ONE:
SHOT GUN SEQUENCING. LED BY CRIAG VENTER [B. 1946]
THEY DID—
SAME THING WITH LAND MARKS, BUT A COMPUTER DID THE WORK; AS BEFORE 800 BASE FRAGMENTS, FEED IT ALL INTO THE COMPUTER TO LINE IT UP— A WHOLE NEW FIELD WAS INVENTED— THIS SHOT GUN SEQUENCE WAS CALLED BIOINFORMATICS.
WAY MORE RAPID; TOOK ONLY A YEAR TO SEQUENCE ETC.
WHEN THE FIRST WAY WAS UNDERTAKEN BY COLLINS, THE COMPUTER STUFF JUST WAS NOT THERE, IT STILL HAD TO BE INVENTED.
WHAT INFORMATION CAN WE GET FROM GENOME SEQUENCING?
1. CODING - OPEN READING FRAMES.
A MACHINE CAN SCAN ALONG A CHROMOSOME SEQUENCE— “O LOOK THAT’S A PROMOTER, I’VE SEEN IT BEFORE.” OR—
“O LOOK THERE ARE THOSE CODON— THE THREE BASE CODE WORDS IN mRNA.”
THEY CODE FOR PROTEINS, DIFFERENT THAN RANDOM, DNA, FOR IT HAS THE PROMOTER THERE; IT’S LIKE A CAPITAL LETTER STARTING A SENTENCE; OR INDENTATION AT THE BEGINNING OF A PARAGRAPH. INFORMATION FROM GENOME.
2. PROTEIN AMINO ACID SEQUENCE
3. ANNOTATION— THE FUNCTION OF THE PROTEIN.
A NUMBER OF NON-HUMAN GENOME HAVE BEEN SEQUENCED.
THE MODEL ORGANISM IN ITS CLASS; MODEL FIRST AND THEN OTHERS IN ITS CLASS.
HUGE INFORMATION, SO COMPARATIVE GENOMICS.
A COMPUTER GATHERS INFORMATION AND SENDS IT TO A LARGER COLLECTING COMPUTER IN THE SKY, WELL NOT REALLY IN THE SKY; USUALLY IN PLACES LIKE WASHINGTON D.C. OR LONDON, OR PLACES IN EUROPE.
THE INFORMATION WE HAVE IS AWSOME TODAY!
SO SUPPOSE WE HAVE A SEQUENCE OF A HUMAN GENE, WE HAVE PROTEIN, AMINO ACIDS, BUT NOT SURE HOW IT MAY ALL FOLD UP TO DO WHATEVER.
WE CONTACT THE DATA BASE HUGE STORAGE COMPUTER AND ASK IF THERE IS SOMETHING LIKE THIS….. WHATEVER WE HAVE.
IT MAY ANSWER AND SAY, “WELL THERE’S A RECEPTOR LIKE THIS IN THE FRUIT FLY.”
MAYBE THEN IT MAY BE LIKE A RECEPTOR IN THE HUMAN.
NON-HUMAN SEQUENCING BEGAN WITH BACTERIUM.
FIRST DONE A LONG LONG TIME AGO— 1995!
THIS WAS DONE ON BACTERIUM WHICH CAUSES MENINGITIS—— IT HAD 1,830,137 BASE PAIRS AND 1,743 PROTEIN CODING GENES.
WHEN IT WAS PUBLISHED IT WAS A SENSATION IN BIO-LOGICAL THINKING!
I NEVER THOUGHT IN MY LIFE’S CAREER I’D SEE THIS DONE!
WE SAW THE GENE ATTACHED TO AND CAUSE MENINGITIS.
YEAST
12 MILLION BASE PAIRS AND 6,000 GENES.
A WORM
THE MODEL COMPLEX IS A WORM— ONLY 1,000 CELLS BUT AMAZING, ONLY A COUPLE OF MILLIMETRES IN SIZE AND TRANSPARENT. BUT HAS REPRODUCTIVE SYSTEM, BASIC NERVOUS SYSTEM, DIGESTIVE SYSTEM, ORGAN SYSTEM, COMPLEX— ALL THOSE CELLS FROM ONE SINGLE CELL - AMAZING - CAN WATCH IT DEVELOP OVER THREE DAYS, AS IT FORMS.
IT HAS 97 MILLION BASE PAIRS IN ITS 19,000 PROTEIN CODING GENES.
RICE
430 MILLION BASE PAIRS AND 35,000 GENES.
THERE IS LOTS TODAY ABOUT AGRICULTURAL GENETICS.
THE HUMAN GENOME
THE TWO GROUPS, GOVERNMENT FUNDED AND PRIVATE FUNDED. ANNOUNCED THEIR FINISHED WORK IN 2,000— COLLINS AND VENTER WITH PRESIDENT CLINTON—- A FINAL DRAFT IN 2003.
HUMANS HAVE 3.2 BILLION BASE PAIRS, LESS THAN 2% CODE FOR PROTEINS. 98% NOT CODING FOR PROTEINS.
24,000 GENES IN THE HUMAN— RICE HAS 35,000 GENES.
I CONSIDER THAT A MAJOR UP-FRONT!
I THINK I’M MORE COMPLEX THAN A RICE PLANT!
THE AVERAGE GENE SIZE IS 27,000 BASE PAIRS INCLUDING ITS PROMOTER.
OVER HALF HAVE SHORT REPEATED SEQUENCE THAT DO NOT CODE FOR PROTEINS.
99% GENOME IS IDENTICAL IN ALL PEOPLE!
1% DIFFERENT—— WELL LOOK AROUND AND SEE THE DIFFERENCES IN US.
1% IS STILL A LOT OF BASE PAIRS!
A GOOD AMOUNT OF THESE FUNCTIONS, OF SOME PROTEIN CODING GENES ARE NOT YET KNOWN [AS OF 2007]. WE’RE STILL FINDING OUT.
OTHER ORGANISMS HAVE SEQUENCES VERY SIMILAR TO HUMAN GENES.
THE WORM I TALKED ABOUT, 19,000 GENES— SOME VERY SIMILAR TO GENES WE HAVE.
HUMBLING!
GENOME SEQUENCING IS GETTING FASTER AND FASTER AND CHEAPER.
IN 2007 - 2 MONTHS - 2 MILLION DOLLARS.
DOWN AND DOWN IT GOES, WITHIN A YEAR OR TWO [AS I SPEAK IN 2007] MAYBE $10,000.
BY ABOUT 2015 MAYBE GENE SEQUENCING FOR $1,000.
WHY DO IT?
1. SCREENING FOR DISEASES
2. WHAT WE HUMANS ARE
SO WE MAY SAY THERE IS A PROBLEM WITH US HAVING TOO FEW GENES. I AM INSULTED THAT I HAVE FEWER GENES THAN THE RICE PLANT!
BUT AS I SAY TO MY STUDENTS, Ph.D. PEOPLE LIKE MYSELF HAVE TWICE AS MANY GENES BECAUSE OF OUR COMPLEX BRAINS. MY STUDENTS START TO WRITE IT DOWN— THEY STOP! THEY LOOK UP, PUT THEIR PENS DOWN AND SAY, “HE’S GOT TO BE KIDDIN’.”
NO, WE ALL HAVE 24,000 GENES.
THREE EXPLANATIONS FOR SO FEW GENES, AND SO GREAT A COMPLEXITY.
1. GENES ARE INTERRUPTED IN GENE SEQUENCE WITH ALTERNATE RNA SPLICING. BY NON-CODING SEQUENCES. CALLED “INTRONS”— KINDA NONSENSE.
FOR EXAMPLE:
I COULD SAY “THIS COURSE IS GOOD”— THAT’S INFORMATION.
BUT IN DNA THAT CODES FOR “THIS COURSE IS GOOD” MIGHT BE INTERVENING WORDS—
“THIS TEACHING COMPANY, HAIR FOLIC, LEFT TOE, COURSE, PRESIDENT, VICE PRESIDENT OF SENATE, IS, DIRT, AIR, WATER, GOOD.”
NOW WE HAVE TO GET RID OF WORDS TO MAKE SENSE OF IT ALL.
THIS IS DONE BY NUCLEUS.
WE HAVE TO CUT, SLICE, IN NUCLEUS.
WE COULD PUT TOGETHER “THIS COURSE GOOD” AND LEAVE OUT ‘IS’— OR “THIS IS GOOD.”
WE CALL IT ALTERNATE SPLICING.
AND IT HAPPENS TO MAKE PROTEINS.
IN FACT EVERY PROTEIN CODING GENE HAS INTRON - INTERVENING SEQUENCES— AND CODING REGIONS CAN BE MISS-AND-MATCH TOGETHER.
EACH CODING GENE IN HUMANS GIVES ABOUT 5 PROTEINS.
SO WE DON’T JUST HAVE 24,000 PROTEIN CODING GENES, WE HAVE ABOUT 120,000 DIFFERENT PROTEINS.
2. POST-TRANSLATIONAL MODIFICATION
AFTER A CODING PROTEIN FOLDS INTO ITS SHAPE OTHER THINGS HAPPEN TO IT, SUGAR COATING CAN HAPPEN, LIKE A SUGAR COATED DONUT. SO SUGARS CAN BE PUT ON TO PROTEINS. SO WE HAVE A WHOLE BUNCH OF GENES AND PROTEINS WITH SUGAR. THREE SUGARS IN ONE PLACE, FIVE IN ANOTHER PLACE, WITH DIFFERENT FUNCTIONS.
VERY OFTEN PROTEINS ACT AS A FLAG OUTSIDE THE CELL. SO A CELL BINDS TO ANOTHER CELL - IMPORTANT IN CANCER RESEARCH.
SO MANY PROTEINS CAN BE MADE, SO MAKING A PROTEIN IS NOT ENOUGH, YOU CAN ADD THINGS TO IT TO CHANGE ITS FUNCTION AND STRUCTURE.
3. THERE IS A CHUNK OF THE 98% HUMAN GENOME THAT ACTUALLY MAKES RNAs THAT DON'T GET OUT OF THE NUCLEUS - THEY STAY IN - THEY’RE CALLED microRNA, AND VERY RECENTLY DISCOVERED [AS OF 2007], THEY ARE NOT YET [2007] IN THE TEXT BOOKS.
HUMANS MAKE A LOT OF THEM.
AND THESE RNA MAYBE INVOLVED IN GENE REGULATION - TURNING A GENE ON OR OFF, AND A GENE MAKING A PROTEIN OR NOT MAKING A PROTEIN, MAKING A messenger RNA OR NOT MAKING A messenger RNA.
WE ARE NOT SURE [AS OF 2007] WHAT ALL RNA ARE DOING BUT HUMANS MAKE A LOT OF THEM, AND THEY ARE OBVIOUSLY INFORMATION AS PART OF THE GENOME.
SCIENTISTS USE TO SAY THE PART OF THE 98% OF GENOME, THAT DOES NOT CODE FOR PROTEINS WAS JUNK! WELL THE JUNK YARD DOES HAVE SOME GENES THERE, AND THE GENES ARE microRNA AROUND THE NUCLEUS— SOMETHING PRETTY IMPORTANT FOR GENES.
SO HUMANS DO MUCH MORE WITH GENES THAN WE EVER THOUGHT!
THAT FRONTIER WAS REALIZED WHEN THE SIMPLE “mycroplasma GENTITALIUM— 482 GENES, LIVES IN THE GENITAL AREA.
THIS GENOME IS THE SMALLEST IN NATURE [UP TO 2007] - IT HAS 482 GENES.
USING TECHNOLOGY OF MANIPULATING GENES, SCIENTISTS HAVE BEEN ABLE TO ACTIVATE ONE AT A TIME. AND ASK THE FOLLOWING QUESTION, “DOES THE CELL SURVIVE?”
YOU TAKE GENE ONE AND KNOCK IT OUT. YOU ASK THE CELL, “ARE YOU STILL ALIVE?” IF SO, IT DOES NOT NEED THAT GENE.
IF THE CELL DIES, THAT GENE WAS NEEDED!
THE END RESULT, IT WAS FOUND 100 GENES WERE NOT NEEDED - 382 WAS ALL THAT CELL NEEDED TO SURVIVE AND LIVE!
ALL 382 WERE ESSENTIAL FOR LIFE!
GENES FOR CODING PROTEINS FOR BASIC CELL STRUCTURE, RIBOSOME, ENZYMES, MAKING RNA ETC. THINGS ALL CELLS HAVE TO DO.
CRAIG VENTER AND HIS COLLEGES IN PRIVATE ENTERPRISE, ARE TRYING TO MAKE THESE 382 GENES IN THE CHEMISTRY LAB.
SYNTHETIC BIOLOGY!
A T G C
TELL THE MACHINE TO….. TINKER-TOY CHEMISTRY—— PUT A WITH T G WITH C
YOU CAN MAKE 382 GENES INDISPENSABLE FOR LIFE—— A VERY SMALL BACTERIUM LIVING IN THE GENITAL TRACK, BUT LIFE!
THEN THEY WANT TO PUT ALL THESE GENES TOGETHER - 382 IN A GENOME - PUT THEM IN AN EMPTY CELL AND MAKE LIFE.
IS THIS JUST A STUNT? NO!
BECAUSE IF YOU CAN DO THAT, YOU CAN TAKE ANY GENE YOU WANT AND WELL…. MAKE SOME TO MAKE PLASTIC, AND MANY MORE THINGS.
YES COULD MAKE RICIN WHICH IS VERY TOXIT— biological WARFARE!
A NEW FIELD IS CALLED SYNTHETIC BIOLOGY— MAKING ARTIFICIAL CHROMOSOMES, MAKING DNA, BECAUSE WE KNOW GENOME SEQUENCES AND PUTTING INTO EMPTY CELL AND DO THE THINGS YOU WANT IT TO DO.
KNOWLEDGE OF DNA SEQUENCING; KNOWLEDGE OF DNA IN GENERAL, HAS ALLOWED SCIENTISTS TO MANIPULATE IT.
End Quote
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WELL QUITE THE INSIGHTS INTO WHAT WE ARE FINDING OUT ABOUT THE DEPTH OF LIFE ITSELF—— GOD IS THE GREATEST SCIENTIST!
MAN COULD NOW MANIPULATE TO THE DETRIMENT OF HUMAN LIFE ON EARTH.
THERE IS THE SIDE OF GOOD USE AND ALSO THE SIDE OF EVIL USE.
BUT I WANT YOU TO CONCENTRATE ON THE MASTERFUL PHYSICAL SCIENCE, TO ALL THIS, THAT PROVES THERE MUST BE A MASTERFUL MIND BEHIND IT ALL.
THE PUTTING OF DNA CODES ETC. INTO THE RIGHT AMOUNT AND ORDER, MAKES AN ELEPHANT, OR A LION, OR AN OWL, OR A HORSE, OR A DOG, OR AN EAGLE, OR A DOLPHIN, OR A GREAT WHALE AND ON AND ON WE COULD GO.
YES AND ALSO MAKING A HUMAN PERSON.
BUT SCIENCE CAN ONLY LOOK AT THE PHYSICAL, HENCE THEY WONDER WHY OUR BRAIN CAN DO THINGS, INVENT THINGS, MAKE THINGS, THAT NO ANIMAL CAN COME CLOSE TO DOING. ONLY MANKIND CAN HAVE A SENCE OF RIGHT AND WRONG. AN ANIMAL CANNOT UNDERSTAND WHAT IS SIN. ANIMALS CANNOT SIN! BUT HUMANS CAN! HUMANS ALONE CAN DETERMINE TO SET DOWN A CODE OF MORAL CHARACTER WITHIN ITS SOCIETY, BREAK IT AND A PENALTY IS FORTHCOMING.
ONLY HUMANS CAN HAVE CONTACT WITH REAL MIND-SET TO BE WITH A GOD THAT WANTS TO BE WITH THEM. THEY ALONE HAVE A MIND THAT CAN CONNECT WITH GOD, ADMIT HE LIVES AND WORKS IN ALL THIS WORLD CONTAINS AND THE SAME FOR THE UNIVERSE.
THE GREATEST PROOF THAT A GOD BEING EXISTS, IS THE PHYSICAL STUFF WE ARE GETTING TO UNDERSTAND MORE AND MORE, IN OURSELVES, HOW WE ARE MAKE, AND THEN HOW THE UNIVERSE IS BUILT.
BOTH ARE BLOWING OUR MINDS IN THE WONDERMENT OF IT ALL.
BUT THERE IS SOMETHING THAT HUMANS HAVE THAT HAVE, IN A DIFFERENT WAY, THAN OTHER LIVING CREATURES—— THE IS A SPIRIT IN MAN!
IT IS INVISIBLE—— IT IS “SPIRIT” NOT PHYSICAL; NO IT IS NOT GOD’S HOLY SPIRIT; A SPIRIT WE ARE BORN WITH; IT’S UNITED WITH OUR BRAIN, AND ALL THINGS BEING NORMAL, WE CAN THINK, AND PLAN, AND WORK, AND DO ALL THAT HUMANS CAN DO, WHICH ANIMALS CAN NOT DO.
I’D GIVE YOU MILLION YEARS OR MORE MILLIONS—— YOU PUT OUT 120 MONKEY ON AN ISLAND, WITH ENOUGH FOOD, WATER, AND JUST ALL THEY NEED TO LIVE A SMOOTH PLEASANT LIFE—— I GIVE THE BEST COMPUTERS IN THE WORLD, NEVER RUN DOWN, NEVER CRASH—— I GIVE YOU A MILLION YEARS; AND THOSE MONKEYS WILL NEVER EVER WRITE WIKIPEDIA !
GOD DOES EXIST AND ONLY THE FOOL HAS SAID IN HIS HEART THERE IS NO GOD!
YES THAT SENTENCE IS IN THE HOLY BIBLE.
YOU NEED TO READ MY IN-DEPTH STUDY CALED “A CHRISTIAN’S DESTINY” AND FIND OUT WHY YOU ARE HERE—- THAT STUDY ALONE WILL BLOW YOUR MIND!
YOU WILL FIND IT UNDER THE “SALVATION” SECTIONS OF THIS WEBSITE.
WONDER OF GENETICS
ISOLATING GENES AND DNA
DAVID SADAVA Ph. D. From the “Teaching Company” - 2007
Quote:
MY OPENING STORY IS ABOUT MUSCULAR DYSTROPHY [MS].
THE FIRST DESCRIPTION OF MS WAS FROM GILLAUME AMEND DUCHENNE [1806 - 1875].
HE NOTICED PROGRESSIVE MUSCLE WASTING AT THE PELVIC AND CALF MUSCLES BEFORE AGE 5, AND THE INABILITY TO WALK BEFORE AGE 12. THIS SPREAD TO OTHER MUSCLES AND DEATH IN THE 20s DUE TO BREATHING MUSCLES NOT ABLE TO FUNCTION, AND WOULD JUST GIVE OUT.
THIS MS IS INHERITED AS A RECESSIVE ALELE ON THE X CHROMOSOME…… MOST COMMON IN MALES—- ONE IN 3,500 BIRTHS. IF YOU THINK THAT IS LOW REMEMBER THERE ARE ABOUT 4 MILLION BIRTHS IN THE USA A YEAR, SO THAT’S OVER ONE THOUSAND BOYS BORN WITH THIS DISEASE.
THE TREATMENT REMAINS SYMPTOMATIC, THAT IS BRACES AND WHELL CHAIRS AND VENTILATORS TO HELP THEM BREATH, THERE IS NO CURE [AS OF 2007].
FOR DECADES SCIENTISTS HAD LOOKED IN THE MUSCLE TISSUE, FOR A DIFFERENCE IN THE NORMAL MUSCLE AND THE MUSCLES OF THOSE WITH MS.
THERE ARE COMMON PROTEINS IN THE MUSCLES.
THEY KNEW MUSCLE FIBRE FELL APART IN MS PATIENTS. NO GOOD INTEGRITY, AND GET REPLACED WITH FATY TISSUE AND NON-MUSCLE FIBRE TISSUE.
BUT THEY COULD NOT FIND THE DIFFERENCE IN THE MUSCLES PER SE WITH THOSE WITH MS AND THOSE WITH NO MS.
IT WAS LIKE LOOKING FOR A NEEDLE IN A HAY-STACK!
BUT METHODS FOR ANALYZING DNA AND CHROMOSOMES TOOK A DRASTIC FORWARD STEP IN THE 1980s.
BY THE MID-80s SCIENCE WAS READY TO TAKE ANOTHER APPROACH TO MS. LET’S FIND THE GENE FIRST AND THEN FIGURE THE PROTEIN—— CALLED REVERSE GENETICS—— THE GENE ISOLATED BEFORE THE PROTEIN.
THE TYPICAL WAY WAS TO FIND THE PROTEIN THEN FIND THE GENE. BUT NOW IT WAS FIND THE GENE FIRST.
AT THE HARVARD MEDICAL SCHOOL, A SCIENTIST LOUIS KUNKEL AND COLLEGES, SAW A BOY WITH MS, AND WHEN THEY LOOKED AT HIS CHROMOSOME UNDER THE MICROSCOPE, THEY SAW THIS BOY WAS MISSING A SMALL PIECE OF DNA IN HIS X CHROMOSOME.
THERE WAS A WOMAN WHO WAS XY [Y BEING FOR MALE] IN HER CHROMOSOME, AND THEY SAID SHE SHOULD BE MALE, BUT THERE WAS A PIECE MISSING IN THE Y AND SO HE WAS A SHE.
LIKEWISE KUNKEL FOUND A PIECE MISSING IN THIS BOY’S X CHROMOSOME, “O THAT MIGHT BE THE GENE FOR NORMAL MUSCLE INTEGRITY THAT’S MISSING IN THIS CASE WITH THIS MS BOY!”
BY 1985 THEY HAD ISOLATED THE GENE THAT WAS MISSING IN MUSCULAR DYSTROPHY.
THE DYSTROPHIN GENE AS THEY CALL IT IS HUGE! IN FACT IT IS THE LARGEST GENE IN THE HUMAN GENOME—— IT HAS 2.5 MILLION BASE PAIRS; AND m[messenger]RNA IS 14,600 BASE PAIRS.
THE AVERAGE GENE IS 27,000 BASE PAIRS.
THE messengerRNA WHICH MAKES THE COPY THAT GOES TO THE RIBOSOME IS 14,600 BASE PAIRS LONG; ONE IS HUGEY LONG, AND ONE WAY SHORTER IN COMPARISON.
WE HAVE “INTRONS”— INTERVENING SEQUENCES— THIS EXTRA STUFF WE HAVE TO GET RID OF BY SPLICING ETC. THE GENE IS IN 79 PIECES, AND WE HAVE TO GET RID OF 78.
COMPLICATED SPLICING THAT GOES ON IN THE NUCLEUS OF THE GENE, BUT IT DOES PRETTY WELL.
NOW ONCE YOU HAVE THE GENE HOW ARE YOU GOING TO GET THE PROTEIN?
RECOMBINANT DNA—— WE TAKE THIS GENE AND PUT IT INTO A BACTERIAL CELL OR HUMAN CELL, THAT DOESN’T HAVE THE GENE AND ALLOW IT TO EXPRESS ITSELF, AND LOW AND BEHOLD THEY HAD THE PROTEIN, CALLED DYSTROPHIN PROTEIN.
IT IS 0.002%—— TWO THOUSANDTH OF MUSCLE PROTEIN!
IT REALLY IS A NEEDLE IN A HAY-STACK. BUT IT’S A VERY IMPORTANT PROTEIN, THIS DYSTROPHIN PROTEIN—- IT CONNECTS MUSCLE FIBRE TO THE OUTSIDE OF THE MUSCLE CELL.
AND SO WHEN THE MUSCLE CONTRACTS, IF THIS CONNECTING THING IS NOT THERE THE MUSCLE LOOSES ITS INTEGRITY; ULTIMATELY THE MUSCLE DIES. FATY TISSUE AND OTHER BAD STUFF COMES IN TO REPLACE IT.
BEFORE RECOMBINANT TECHNOLOGY THEY COULD NOT HAVE DONE IT THIS WAY.
GENE FIRST AND THEN THE PROTEIN!
NOW THEY IDENTIFIED THE GENE. NOW THEY HAVE THE PROTEIN!
SO WHAT?
YOU READ IN PAPERS, “SCIENTISTS IDENTIFY GENE AND PROTEIN RESPONSIBLE FOR……” WHATEVER.
AND YOU SAY “THEN, THEN, THEN……”
IN MS THE APPROACH NOW IS TO TRY TO GET THE BODY TO MAKE THE MISSING PART OF THE X—— DYSTROPHIN.
THERE IS A PROTEIN VERY SIMILAR—— UROTROPHIN.
IT CAN GO INTO THE MUSCLE AND REPLACE DYSTROPHIN. BUT THE BODY MAKES LITTLE OF IT.
THERE IS NOW A HUGE EFFORT TO DEVELOP DRUGS THAT WILL HIPE UP THE BODY TO MAKE UROTROPHIN THAT CAN REPLACE DYSTROPHIN.
THIS COULD NEVER HAVE HAPPENED IF WE DID NOT KNOW WHAT DYSTROPHIN WAS.
SECOND— ADDING BACK THE ENTIRE GENE—— GENE THERAPY—— TAKING GOOD GENES AND ADDING IT BACK TO THE DISEASED TISSUE.
THIS WHOLE FIELD IS CALLED— MOLECULAR MEDICINE.
BACK TO COMPARING DNA
SOL SPIEGELMAN [1914 - 1983] GAVE US IN THE 1960s WHAT IS CALLED HYBRIDIZATION TECHNIC.
SUPPOSE DNA HAS…. WELL TO MAKE IT EASY— AAAGGGCCCTTT
WE UNDERSTAND THE OTHER STRAND AS ITS COMPLIMENT—
TTTCCCGGGAAA
NOW IS THAT GENE KNOWN IN SOME DNA WE HAVE?
YOU MAKE THE OPPOSITE
TTTCCCGGGAAA
YOU TAKE THAT AND PUT IT ON SOME FILTER PAPER OR STATIONIZE IT IN SOME WAY.
WE TAKE OUR UN-KNOWN DNA AND UN-ZIP IT. ALL THE DNA WASHES OVER IT AND THE ONLY UNKNOWN DNA TO BIND TO IT IS THE COMPLIMENT DNA—— AAAGGGCCCTTT
IF NOTHING BLINDS TO IT THEN OUR OUTSIDE DNA DOES NOT HAVE
AAAGGGCCCTTT
WE ARE LOOKING FOR “COMPLIMENT” DNA ON THE FILTER PAPER AND THE ONE FROM A DIFFERENT SOURCE— HYBRID DNA.
IT’S LAB WORK. HYBRID— ONE DNA FROM ONE PLACE, ONE DNA FROM ANOTHER PLACE, AND HAVING THEM BIND.
SO BACK TO KUNKEL’S DILEMA OF MS.
KUNKEL HAD AN INTACT X CHROMOSOME AND THE ABNORMAL X CHROMOSOME, MISSING SOME DNA.
HE TOOK THE LONG PART OF THE CHROMOSOME AND HYBINATED THEM TO EACH OTHER. ONE STRAND FROM THE MS PATIENT AND ONE STRAND FROM NORMAL DNA.
THEY MATCHED, EXCEPT— A LOOP HAPPENED WHERE THE MISSING DNA WAS— THERE WAS NO COMPLIMENT TO BIND TO.
THEY STRUCK OUT THE LOOP PUT IN A CLONING VECTOR AND THEY HAD THE GENE.
[IF YOU ARE GETTING ALL THIS YOUR DOING BETTER THAN ME - Keith Hunt]
THAT IS HOW THEY FOUND THE GENE IN MS……..
DNA LIBRARIES
RAPID SCREENING OF THE GENOME CAN BE DONE BY DNA LIBRARIES— USED FOR RAPID SCREENING OF GENOME.
IT’S NOT A LIBRARY OF BOOKS OF DNA.
IT’S A VOLUME OF GENO ALL DISPLAYED IN SOME WAY.
DNA LIBRARIES IS MADE BY GENE CLONING.
HOW? WHY?
WHY WE DO IT IS THE FOLLOWING:
FOR EXAMPLE— MS IN THESE BOYS.
SURE THEY WERE MISSING A SMALL PART OF THE X CHROMOSOME. WERE THEY MISSING ALL OF THAT DYSTROPHIN GENE? THAT LOOP THAT KUNKEL SAW; WAS THIS THE WHOLE GENE? THEY WERE MISSING PART OF THE PROTEIN AND IF YOU MISS SOME IT DOES NOT FUNCTION AS IT SHOULD IF ALL WAS THERE. IF ONLY PART OF THE PROTEIN IS THERE, IT DOES NOT FOLD CORRECTLY AND DOES NOT DO WHAT IT IS SUPPOSED TO DO.
SO WHERE WAS THE REST OF THE GENE AND HOW ARE THEY GOING TO FISH IT OUT?
YOU TAKE THE GENOME AND CUT IT INTO PIECES.
YOU TAKE EACH ONE OF THESE PEICES AND RANDOMLY PUT IT INTO A VECTOR FOR CLONING. SAY THE GENOME IS RED — WE HAVE PART CIRCLES OF RED, BUT NOW WE ADD A VECTOR, SAY IT IS BLUE. WE HAVE CIRCLES OF RED WITH A PART THAT IS BLUE— THE VECTOR.
WE CAN HAVE THOUSANDS OF VECTORS WITH A GENE IN IT— SAY A HUMAN GENE— SAY WE HAVE 24,000. WE PUT THEM INTO BACTERIA— 24,000.
WE GROW THEM UP AS LITTLE COLONIES, YOU’VE SEEN IT IN YOUR KITCHEN IF YOUR NOT CAREFUL, LIKE FUNGI COLONIES.
EACH COLONY HAS A HUMAN GENE IN IT.
WE CAN TAKE DNA FROM EACH, SEPARATE THE TWO STANDS; USE A PROBE, LIKE DYSTROPHIN GENE— WELL HALF OF IT WE SEND IT TO BIND, BUT ONLY BINDS WHERE IT CAN; YET IT WILL FISH OUT THE REST OF THE GENE WITH IT.
[GOOD FOR YOU IF YOU GET ALL THIS, MY MIND AIN’T SO SCIENTIFIC - Keith Hunt]
IT’S LIKE:
WHOLE GENE ——————----
PROBE ————— HALF GENE
PROBE ATTACHES TO THE WHOLE GENE, BUT ONLY WHERE IT CAN, BUT IT PULLS OUT THE REST OF THE GENE FROM THE BACTERIAL CELL.
A BEAUTIFUL TECHNIC!
[WELL DAVID SADAVA SAY IT IS; HE’S THE Ph.D. GUY SO I GUESS IT IS - Keith Hunt]
PROBLEM:
WE HAVE 24,000 BACTERIAL COLONIES. KINDA A HASTLE TO DO.
ONCE WE HAVE IDENTIFIED THE COLONY THAT HAS THE ENTIRE GENE, WE CAN PICK THAT COLONY OUT, PUT THE COLONY CELLS INTO A LIQUID MEDIUM AND BY TOMORROW, WE HAVE A LOT OF THAT GENE. WE GROW A LOT OF THE CELLS THAT HAVE THE VECTOR, THAT HAS THE GENE IN IT. WE CAN RE-ISOLATE THAT VECTOR, BURST OPEN THE CELL, TAKE OUT THE VECTOR THAT HAS THE HUMAN GENE IN IT; AND BECAUSE THE VECTOR WAS CREATED BY RECOMBINANT DNA TECHNICS WHEREBY YOU USE A RESTRICTION ENZIME, WE TAKE THE SAME RESTRICTION ENZIME, WE CAN CUT OPEN THE VECTOR AND OUT POPS THE GENE.
A TERRIFIC WAY TO ISOLATE A HUMAN GENE THAT’S IN-TACKED.
IT’S CALLED A HUMAN GENE LIBRARY.
[WELL IT’S TERRIFIC FOR SCIENTISTS WITH Ph.D……. FOR ME ANND MAYBE YOU IT KINDA GOES OVER MY HEAD - Keith Hunt]
LIBRARIES HAVE NOW BEEN MINIATURIZED INTO DNA MICROARRAY.
WE DON’T HAVE TO CLONE.
THE SILICONE CHIP WAS A MASTERFUL INNOVATION IN ELECTRONICS IN THE LATE 20TH CENTURY; ELECTRIC CIRCUITS STAMPED ON IT IT.
A MICRO-CHIP DNA IS A SMALL GLASS YOU PUT DNA ON IT…….
NOW THEY HAVE ALL 24,000 GENES ON THEM ARRAYED IN A ROW.
GLASS PROBES FOR ALL 24,000 GENES.
NOW WHY WOULD YOU WANT TO LOOK AT ALL 24,000 GENES?
WELL— IS THE PATIENT MISSING A GENE? IF IT DOES NOT FIND ITS PARTNER, THAT PERSON IS MISSING A GENE.
WE CAN SCREEN FOR MUTATIONS IN DNA.
YOU CAN ALSO HYBRANIZE RNA.
WE’RE USING FANCY EQUIPMENT TO SEE ALL THIS, WE’RE NOT LOOKING AT IT UNDER A MICROSCOPE; A LASER SCANNING OVER IT, AND SUCH LIKE.
IF WE TAKE A TISSUE AT A CERTAIN TIME IN ITS LIFE, WE TAKE ALL THE RNA - messengerRNA, THOSE ARE THE RNA THE TISSUE IS EXPRESSING AT THAT TIME. DIFFERENT RNA AT DIFFERENT TIMES. THE RED BLOOD CELL MAKES THE RNA FOR HEMOGLOBIN; THE HAIR CELL THE RNA FOR HAIR ETC.
WE TAKE ALL THE RNA ON A CIP SO TO SPEAK, WE CAN FIND ALL THE ONES BEING EXPRESSED, BY THIS TISSUE AT THAT TIME. SO DIFFERENT EXPRESSIONS AT DIFFERENT TIMES—— I DO NOT HAVE HAIR GROWING OUT OF MY BONE MARROW OR BLOOD COMING OUT OF MY HEAD.
THESE HAVE GREAT SIGNIFICANCE!
EXAMPLE:
BREAST CANCER - THE TUMOR - WHAT STAGE IS IT AT? IS IT LOCALIZED OR GOING TO SPREAD?
IF IT LOOKS LIKE IT HAS NOT SPREAD, SURGERY IS DONE, AND MAYBE “GOT IT ALL.”
BUT THAT CAN BE A QUESTION— THE TUMOR MAYBE HIDING IN OTHER PLACES— IT’S SPREAD.
A SMALL TUMOR MAY HAVE ABOUT A BILLION CELLS.
WHAT PHYSICIANS LIKE TO KNOW IS HAVE THEY GOT IT ALL? LOOKING AT THAT TUMOR, IS THERE SOMETHING IN IT THAT SAYS, “I’M THE SPREADING TYPE” OR ONE THAT SAYS “I’M ALL HERE, I’M NOT SPREADING.”
UNDER THE MICROSCOPE THE CELLS LOOK ALIKE. UNDER CHEMICAL TESTING WE MAY FIND THE CELLS HAVE SPREAD, SO AFTER SURGERY WE TREAT WITH RADIATION OR DRUGS TO KILL CELLS ELSEWHERE IN THE BODY.
DR. LAURA VAN’T VEER, AT THE NETHERLANDS CANCER AGENCY——
SHE TOOK A BIOPSY FROM BOTH TUMOR IN RETROSPECT, FROM NOT SPREADING AND FROM ONE THAT DID SPREAD.
SHE ASKED WHICH WERE EXPRESSED. SOME GENES EXPRESSED MORE IN SPREADING TUMOR; SOME GENES EXPRESSED MORE IN “NOT” SPREADING TUMOR.
SHE HAD A GENE EXPRESSING SIGNATURE, IF DONE EARKY ON.
SO DO GENE EXPRESSING PROBE AS DESCRIBED BEFORE, YOU CAN KNOW WHAT YOUR DEALING WITH—- EXPRESSION TO SPREAD OR NOT TO SPREAD.
SYNTHETIC DNA CAN BE USED TO MAKE NEW GENES AND MUTATIONS.
CHEMISTS KNOWING THE GENETIC CODE CAN MAKE IN THE LAB ONE BY ONE STEP INTO GENES; HENCE ALSO MAKING MUTATIONS.
WE HAVE AN ENZIME THAT HAS THIS FUNCTION, WHAT IF WE HAVE IT FOLD IN A DIFFERENT WAY, WILL IT HAVE A DIFFERENT FUNCTION?
SO INSTEAD OF A A G WE MAKE A G A IN OUR AMINO ACIDS.
WE CAN LOOK UP GENETIC CODE AND CHANGE GENES AT WILL; WE ARE NO LONGER RELYING ON THE ACCIDENTS OF MUTATION IN NATURE.
WE CAN CREAT MUTATIONS IN THE LABORATORY.
IN THE NEXT LECTURE WE CAN SEE WHAT HAS BEEN MADE WITH RECOMBINANT DNA.
End Quote
……………….
WELL THAT IS GETTING AT THE NITTY-GRITTY OF GENETICS; HARD TO FOLLOW IF LIKE ME YOU DID NOT TAKE SOME OF THIS IN HIGH SCHOOL.
WE SHOULD THOUGH BE ABLE TO SEE THE DEPTH OF WHAT SCIENTISTS HAVE AND ARE FINDING OUT.
WE ARE INDEED WONDERFULLY MADE, AS IS ALL THIS PHYSICAL EARTH, ALL OVER IT, ON IT, AND UNDER IT.
TO THINK THAT ALL THIS DNA STUFF JUST KINDA FORMED ITSELF, EVEN GIVEN MILLIONS OF YEARS AS EVOLUTIONISTS WANT TO GIVE; WITH MISTAKES IN DNA SOMETIMES OF THE SMALLEST AMOUNT AS IN MUSCULAR DYSTROPHY, WE SHOULD HAVE FOUND UNDER THE GROUND, MANY MANY MIXED UP HUMANS AND ANIMALS, AS DNA WAS TRYING TO FORM ITSELF.
WE HAVE NOT FOUND THIS IN ARCHEOLOGY!
WE HAVE FOUND PERFECTLY FORMED CREATURES LARGE AND SMALL.
WE HAVE FOUND NICELY FORMED SKELETONS OF HUMANS, AND SOME WE SEE WITH WOUNDS FROM WHICH THEY PROBABLY DIED.
WITH SLOW EVOLUTION WE SHOULD HAVE FOUND MIXED UP HUMANS AND ANIMALS, AS DNA WAS FORMING ITSELF, WITH MANY MISTAKES ALONG THE WAY. BUT SUCH IS NOT THE CASE AT ALL.
THE COMPLEXITY OF DNA, messengerRNA, THE LITTLE MACHINE THAT RUNS ALONG A STRAND OF DNA, CORRECTING MISTAKES…..ALL THAT WE HAVE LEARNT IN THESE LECTURES, IS MIND-BENDING!
THEN WE HAVE THE LAW OF “AFTER ITS KIND”—— HORSES DO NOT MATE WITH COWS; DOGS TO NOT MATE WITH CATS; THE SQUIRREL DOES NOT MATE WITH THE ROBIN; A CROCODILE DOES NOT MATE WITH A DOLPHIN, AND ON AND ON WE COULD GO WITH EXAMPLE AFTER EXAMPLE.
WE HAVE THE LAW OF GRAVITY—— HOW ON EARTH [PUN INTENDED] DID GRAVITY FORM ITSELF, TO BE JUST RIGHT FOR LIFE ON EARTH?
WHY ARE WE JUST AT THE RIGHT DISTANCE FROM THE SUN, SO LIFE ON EARTH CAN EXIST?
WHY CAN MANY THINGS ON EARTH MAKE ALL 20 AMMINO ACIDS, BUT HUMANS CAN ONLY MAKE 12 OF THEM, AND WE MUST GET THE REST FROM OUR DIET?
THERE IS SO MUCH TO LIFE ON THIS PLANET; AS SCIENTISTS DELVE DEEPER AND DEEPER INTO WHAT MAKES LIFE, THE MORE IT SHOULD AMAZE US; THE MORE IT SHOULD SAY TO US, THERE IS A MASTERMIND BEHIND IT ALL—— THE MORE IT SHOULD TELL US THERE IS A GOD, WHO MADE THE UNIVERSE, AND WHO SET PHYSICAL LAWS INTO MOTION.
AS A KID IN A SMALL WELSH VILLAGE, I SAW ALL THE WONDERS OF NATURE AROUND ME. I WAS FASCINATED BY THE BUTTERFLY, THE CATERPILLAR, THE LADY-BUG, THE BIRDS, AND JUST EVERYTHING ALL AROUND ME.
MY DAD SENT ME TO A CHURCH OF ENGLAND SCHOOL WHEN I WAS 7 YEARS OLD. THAT FIRST SCHOOL MORNING WE WERE GIVEN A BIBLE, AND THE TEACHER TOLD US TO OPEN IT UP AT PAGE ONE. SHE READ TO US “IN THE BEGINNING GOD CERATED THE HEAVENS AND THE EARTH” AND CONTINUED READING.
IT WAS LIKE A LIGHT SWITCH TURNED ON, THE LIGHT FLOODING INTO MY MIND. I CAN REMEMBER LIKE IT WAS YESTERDAY, I SAID, “THAT’S THE ANSWER! THAT’S THE ANSWER TO ALL I SEE AROUND ME— IT IS A GOD BEING WHO MADE ALL THIS!”
AS THE APOSTLE PAUL SAID IN HIS LETTER TO THE ROMANS, THE CREATION SPEAKS OF THE PROOF THAT GOD EXISTS!
TRULY ONLY THE FOOL HAS SAID IN HIS HEART THERE IS NO GOD!
END OF PART ONE
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