- WELCOME TO NUCLEIC ACIDS PART TWO.
IN THIS TUTORIAL,
WE'LL LOOK MORE CLOSELY AT THE STRUCTURE OF DNA.
LET'S GET STARTED. ALL RIGHTY.
SO THE NUCLEIC ACIDS
ARE BASICALLY POLYMERS OF NUCLEOTIDES.
WHAT HAPPENS IS, THE NUCLEOTIDES ARE JOINED
WHEN THE PHOSPHATE OF ONE NUCLEOTIDE
JOINS THE THREE PRIME ALCOHOL OF THE OTHER NUCLEOTIDE
TO FORM PHOSPHATE ESTER OR PHOSPHO ESTER BONDS, ALL RIGHT.
SO LET'S--HERE, IT'S EXPLAINED TO US
BUT LET'S CONNECT THAT TO THE ACTUAL STRUCTURE.
SO WE'RE GOING TO LOOK AT A TRINUCLEOTIDE, ACG.
SO, THE FIRST THING TO NOTE
IS THAT WE READ THEM FROM THE TOP DOWN.
AND SO, THIS IS DESCRIBED AS THE FIVE PRIME TO THE THREE PRIME.
SO, WE START AT THE FIVE PRIME
AND REMEMBER THAT THAT WAS WHERE THE PHOSPHATE GROUP ATTACHED.
AND THEN WE WILL END AT THE THREE PRIME
AND THAT'S WHERE THE LINKS OCCUR
BETWEEN ONE NUCLEOTIDE AND THE OTHER, RIGHT?
AND SO THE OTHER ONE,
AND THEN JUST--SINCE WE'RE TALKING ABOUT--
THE SUGAR IS VERY BUSY, RIGHT?
AT ONE PRIME, THAT'S WHERE THE NITROGEN BASE ATTACHES.
SO, OUT OF THE FIVE CARBON ATOMS,
ON THE--THE FIVE CARBON SUGAR, THREE OF THEM ARE VERY BUSY.
ALL RIGHT. SO, WE LOOK HERE AND WE SEE THERE'S THE FIVE PRIME,
SO THIS IS THE START OF THE SEQUENCE, RIGHT?
SO, FIVE PRIME STARTS THE SEQUENCE.
NOW, EVERY NUCLEOTIDE HAS A PHOSPHATE
AND A FIVE CARBON SUGAR.
SO, WE SEE THAT THE NUCLEOTIDES ARE CLASSIFIED
BY THE NITROGENOUS BASE.
OKAY. SO HERE, WE WOULD HAVE THE FIRST NUCLEOTIDE,
THE PHOSPHATE GROUP AND THE SUGAR
AND THE NITROGENOUS BASE AND THEN HERE IS THE LINKAGE, RIGHT?
SO THIS WOULD BE THE PHOSPHO ESTER BOND OR PHOSPHATE ESTER,
TWO WAYS TO SAY THE SAME THING, RIGHT?
SO HERE IS OUR FIRST NUCLEOTIDE THAT WE CLASSIFY AS ADENINE.
NOW, THIS PROCESS IS GOING TO REPEAT OVER AND OVER.
SO WE LOOK AT THIS PHOSPHATE GROUP RIGHT AT THE FIVE PRIME
AND THERE'S THE ONE PRIME WHERE THE NITROGENOUS BASE, ALL RIGHT.
SO THEN WE HAVE ANOTHER PHOSPHATE ESTER BOND
AND WE SEE THAT THAT PHOSPHATE ESTER BOND AT CARBON THREE
IS THE LINK TO THE NEXT NUCLEOTIDE.
SO WE CAN GO IN HERE,
WE SEPARATE THE NUCLEOTIDES AT THOSE PHOSPHO ESTER BONDS,
SO THEN THIS WOULD BE CYTOSINE.
AND THEN LAST BUT NOT LEAST,
WE BRING IN THE THIRD NUCLEOTIDE AND RIGHT,
WITH THE PHOSPHATE GROUP
LINKING FROM CARBON THREE PRIME OF THE TOP NUCLEOTIDE
TO CARBON FIVE PRIME OF THE BOTTOM NUCLEOTIDE,
GUANINE IN THIS CASE.
AND THEN HERE WE HAVE THE THREE PRIME ENDS THE SEQUENCE.
SO HERE WOULD BE THE NUCLEOTIDE GUANINE, ALL RIGHT.
SO, YOU WANT TO BE ABLE TO CIRCLE
THE INDIVIDUAL NUCLEOTIDES RECOGNIZING THE ROLE
OF THE PHOSPHATE ESTER LINKAGE
TO JOIN THE TWO NUCLEOTIDES TOGETHER.
AND RECOGNIZE THAT WE ALWAYS START AT THE TOP
WITH THE FIVE PRIME OF THE SEQUENCE,
AND WE READ DOWN AND WE END WITH THE THREE PRIME
THAT ENDS THE SEQUENCE.
NOW, WE ONLY HAVE FOUR NUCLEOTIDES.
HOW CAN WE GET SO MANY DIFFERENT GENETIC VARIATIONS?
WELL, THE NUMBER OF NUCLEIC ACIDS THAT CAN BE FORMED
FROM FOUR DIFFERENT NUCLEOTIDES IS FOUR TO THE N.
SO, JUST USING THESE THREE NUCLEOTIDES RIGHT HERE,
FOUR TO THE THIRD IS SIXTY-FOUR DIFFERENT POSSIBLE NUCLEIC ACIDS
AND DNA IS COMPOSED OF MILLIONS OF NUCLEOTIDES.
SO THAT EXPLAINS THE WONDERFUL DIVERSITY THAT WE SEE
AMONG ALL THE DIFFERENT CREATURES ON THIS PLANET. OKAY.
NOW THAT WE UNDERSTAND
HOW A STRAND IS HOOKED TOGETHER OF NUCLEIC ACID,
WE'LL GO INTO THE ACTUAL STRUCTURE OF DNA.
SO, DNA ACTUALLY HAS TWO NUCLEIC ACID MOLECULES,
THEN TWIST TOGETHER AROUND EACH OTHER
TO FORM THE INFAMOUS DOUBLE HELIX.
IT'S IMPORTANT TO NOTE, RIGHT?
SO IT'S BACK AT--IN 1953,
WATSON AND CRICK WERE THE ONES THAT PROPOSED THIS STRUCTURE,
BUT THE PERSON THAT OFTEN--SHE'S GETTING MORE RECOGNITION NOW
BUT HER NAME WAS ROSALIND FRANKLIN,
AND SHE WAS THE WOMAN
WHO ACTUALLY COLLECTED ALL THE X-RAY DIFFRACTION DATA
THAT HELPED WATSON AND CRICK GET TO THEIR DISCOVERY.
AND SO IT'S IMPORTANT TO ACKNOWLEDGE HER CONTRIBUTIONS
AS WELL AS THEIRS.
AND SO, NOW LET'S THINK ABOUT THE NUCLEIC ACID STRUCTURE
AND HOW DOES IT CREATE THIS DOUBLE HELIX, RIGHT?
WELL, THERE'S THE HYDROPHILIC BACKBONE.
SO THIS IS WHERE WE HAVE THE SUGAR, RIGHT,
AND THE PHOSPHATE.
SO WHAT DO WE KNOW, RIGHT, WHY WOULD THOSE BE HYDROPHILIC?
WELL, SUGARS LOVE TO H-BOND WITH ALL THOSE HYDROXYL GROUPS,
AND THE PHOSPHATE GROUP IS IONIC. SO--RIGHT?
SO THIS CREATES THE BACKBONE OR THE RIBBON, RIGHT?
SO CREATES THE--THIS WATER LOVING BACKBONE.
AND SO, SYMBOLICALLY, YOU COULD KIND OF THINK OF IT
AS LIKE THE SIDES OF THE LADDER, RIGHT?
SO THE HYDROPHILIC BACKBONE IS LIKE THIS.
BUT THEN OF COURSE WE NEED--
WE'RE GOING TO NEED TO TWIST IT BUT THAT WILL COME SOON ENOUGH,
RIGHT?
AND SO, RIGHT--BECAUSE THEY'RE WATER LOVING,
THEY WANT TO BE ON THE OUTSIDE--
RIGHT ON THE OUTSIDE TO INTERACT WITH OUR AQUEOUS BODILY FLUIDS.
OKAY. SO NOW WE NEED THE HYDROPHOBIC PART.
YOU COULD THINK OF THIS AS THE RUNGS ON THE LADDER.
SO WE WOULD PUT THOSE HERE, ALL RIGHT?
SO THAT WOULD BE THE HYDROPHOBIC,
NITROGEN BASED PAIRS, RIGHT?
AND SO, THE BEAUTY IS, IS THAT THE NITROGEN--
THE NITROGEN BASES, RIGHT? THEY CAN H-BOND WITH EACH OTHER.
AND THIS IS PERFECT,
IT ADDS ENOUGH STRUCTURAL INTEGRITY TO ACTUALLY FORM
THE DOUBLE HELIX BUT BECAUSE THESE ARE IMF'S, NOT TRUE BONDS,
IT ALLOWS FOR OPENING AND CLOSING.
SO H-BONDS ARE LIKE THE GOLDILOCKS, RIGHT?
THERE'S ENOUGH ATTRACTION TO KEEP TO-
SO THERE'S ENOUGH ATTRACTION, RIGHT?
TO FORM THE HELIX, RIGHT?
BUT THEY'RE ABLE TO OPEN-- BUT ABLE TO SEPARATE
AND WE'LL TALK ABOUT WHY THAT'S IMPORTANT VERY SOON. OKAY.
SO WE'VE TALKED ABOUT IT IN A DESCRIPTION.
NOW LET'S ACTUALLY LOOK AT THE STRUCTURE, RIGHT?
SO HERE WE SEE THE HYDROPHILIC SUGAR PHOSPHATE, RIGHT?
THAT'S THE BACKBONE THERE,
AND THEN WE SEE THE NITROGENOUS BASE PAIRS
FORMING THE RUNGS TO THE LADDER AND THEN INSIDE HERE, RIGHT?
THIS IS REPRESENTING, RIGHT, THE DASHED LINES ARE THE H-BONDING.
SO IF WE SEE HERE--LET'S SEE.
THIS IS ADENINE AND THIS IS THYMINE
AND SO IT'S IMPORTANT TO NOTE THAT ADENINE AND THYMINE,
THEY WILL ALWAYS FORM COMPLEMENTS TO EACH OTHER
AND WE CAN SEE HOW STRUCTURALLY
THEY LINK TOGETHER WITH TWO H-BONDS.
AND THEN, IF WE LOOK AT GUANINE AND CYTOSINE,
THEY ALSO ALWAYS FORM PAIRS TOGETHER,
SO WE'LL ONLY SEE ADENINE
WITH THYMINE AND GUANINE WITH CYTOSINE.
WE NEVER SEE THEM MIXED THE OTHER WAY.
AND HERE, WE SEE THAT THERE'S THE ABILITY
TO FORM THREE H-BONDS AND SO IF WE LOOK HERE--FOR EXAMPLE,
HERE'S ADENINE--OOPS.
HERE'S ADENINE TO THYMINE RIGHT THERE,
SO HERE IT'S SHOWN IN THE SCHEMATIC
AND THIS IS WHAT IT WOULD LOOK LIKE
IF WE GOT DOWN TO THE ATOMIC LEVEL AND THEN HERE--LET'S SEE.
HERE'S GUANINE AND CYTOSINE,
THEN SO THIS IS WHAT IT LOOKS LIKE SYMBOLICALLY
AND THERE WE SEE IT AT THE MOLECULAR LEVEL.
ALL RIGHTY. OKAY.
SO, WE'VE LOOKED TO SEE HOW THE NUCLEOTIDES BOND TOGETHER
TO CREATE THE NUCLEIC ACIDS.
AND THEN WE'VE SEEN HOW THE NUCLEIC ACIDS COME TOGETHER
TO FORM THE DOUBLE HELIX THAT WE RECOGNIZED AS DNA,
AND REMEMBERING THAT
THE NITROGENOUS BASES ARE RESTRICTIVE,
THAT IT'S ADENINE WITH THYMINE AND GUANINE WITH CYTOSINE ONLY.
AND NOW, WE'LL LOOK AT THE HIGHER ORDER OF DNA. RIGHT?
SO, DNA IS PACKAGED INTO CHROMOSOMES
THAT ARE FOUND IN THE NUCLEUS OF THE CELL. RIGHT?
SO, THE CHROMOSOMES ARE HIGHLY COMPACT STRUCTURES.
THEY--AND THEY INCLUDE BOTH THE DNA AND PROTEINS. RIGHT?
SO, WHAT ARE THESE PROTEINS?
THESE PROTEINS ARE CALLED HISTONES.
AND SO, NUCLEOSOME IS A SMALLER--
IS A LOWER LEVEL OF STRUCTURE THAT CREATES THE CHROMOSOMES.
SO, BASICALLY WHAT HAPPENS IS THE DNA GETS WRAPPED AROUND
THESE PROTEINS--THE HISTONES TO CREATE THE NUCLEOSOMES.
AND THEN THESE--THE NUCLEOSOMES
COIL UPON THEMSELVES TO MAKE THE CHROMATIN FIBERS.
AND THEN THE CHROMATIN FIBERS WRAP UPON THEMSELVES
TO CREATE THE CHROMOSOMES.
SO, WE HAVE IT IN WORDS.
AND NOW LET'S LOOK AT A DIAGRAM OF THE HIGHER ORDER.
ALL RIGHT. SO, THIS IS WHERE WE STARTED. RIGHT?
HERE IS THE DOUBLE HELIX OF THE DNA,
TWO STRANDS OF NUCLEIC ACIDS, RIGHT,
THAT ARE POLYMERS OF NUCLEOTIDES.
AND THEN HERE THESE SMALL CIRCLES
ARE REPRESENTING THE HISTONE--
THE HISTONES WHICH WE KNOW ARE PROTEINS. ALL RIGHT.
SO, WE CAN SEE THAT THE DNA CURLS
AROUND THE HISTONES TO CREATE THE NUCLEOSOMES.
AND THEN THE NUCLEOSOMES CURL ON THEMSELVES
TO CREATE THE CHROMATIN FIBER.
AND THEN THE CHROMATIN FIBER CURLS UP ON ITSELF
TO MAKE THE CHROMOSOME.
ALL RIGHT. SO, YOU WANT TO UNDERSTAND.
MAKE SURE YOU'LL UNDERSTAND THE DIFFERENT COMPONENTS
THAT GO IN TO CREATING
THE HIGHER ORDER STRUCTURE OF A DNA MOLECULE.
AND NOW, LET'S LOOK A LITTLE MORE CLOSELY AT--
WE KNOW THAT THE DNA HOLDS THE GENES
OR THE INSTRUCTIONS FOR MAKING--
SYNTHESIZING PROTEINS AND ENZYMES.
SO, LET'S LOOK A LITTLE MORE CLOSELY AT THAT FOR A MINUTE.
ALL RIGHT. SO, THERE HAS BEEN A LOT OF TALK, RIGHT,
THE GENOME IS THE COMPLETE SEQUENCE OF BASES OF DNA
DISTRIBUTED OVER THE 46 CHROMOSOMES.
AND A GENE IS A SEGMENT OF THAT DNA. RIGHT?
SO, THE GENE IS WHERE WE HAVE
THE ACTUAL INSTRUCTIONS FOR MAKING THE PROTEIN.
IF WE LOOK BACK TO OUR INTRODUCTION,
WE TALKED ABOUT DNA AS HAVING THE INSTRUCTIONS
AND THOSE INSTRUCTIONS ARE CALLED THE GENE.
SO, WHEN A GENE IS EXPRESSED.
RIGHT, SO, GENE EXPRESSION, RIGHT, THAT'S WHAT PROMPTS.
RIGHT. PROMPTS. THE SYNTHESIS OF PROTEINS.
AND IN MANY CASES THESE PROTEINS ARE ENZYMES. RIGHT?
SO, IF SOMETHING HAPPENS IN OUR BODY,
WE NEED REACTIONS TO OCCUR THEN WE'LL HAVE GENE EXPRESSION
TO SYNTHESIZE THE PROTEINS WHICH CAN THEN CATALYZE
THE REACTION AS ENZYMES.
SO, JUST TO GIVE YOU A SENSE OF ALL--
OF HOW COMPLICATED THIS ALL IS,
HERE IS AN EXAMPLE OF THE INFORMATION
WE'VE LEARNED ABOUT CHROMOSOME SIX. RIGHT?
AND THERE'S JUST-- IT'S OVERWHELMING,
SO IF THIS IS CURIOUS TO YOU,
YOU CAN READ SOME MORE INFORMATION.
BUT, NOW LET'S LINK THIS
TO WHAT WE'VE LEARNED ABOUT DNA AND CHROMOSOME STRUCTURE,
RIGHT?
SO, HERE'S A REPRESENTATIVE OF THE CHROMOSOME
AND THEN WHEN WE LOOK INSIDE WE RECOGNIZED THAT WE SEE, RIGHT,
WENT THROUGH THE--WE UNRAVEL THE CHROMATIN FIBER,
AND UNRAVEL THE NUCLEOSOMES.
WE GET DOWN TO THE DOUBLE HELIX OF THE DNA.
AND THEN WITHIN THAT THERE IS A GENE, RIGHT?
THERE IS A SEQUENCE. HERE IT IS, RIGHT?
THERE'S THE NUCLEOTIDE SEQUENCE WHICH CREATES A GENE
ON A SINGLE STRAND OF THE DNA.
AND REMEMBER THAT THAT NUCLEOTIDE SEQUENCE
IS THEN THE RECIPE FOR HOW TO MAKE A PROTEIN.
AND REMEMBERING THE--AND SO, THEN WHEN WE SEE A G, OR A "A",
OR A T REMEMBER THAT THAT REPRESENTS ONE NUCLEOTIDE,
AND THAT THEY'RE CHARACTERIZED BY THEIR BASE. OKAY.
SO, LET'S GO INTO A LITTLE BIT ABOUT HOW GENE EXPRESSION WORKS
OR--WELL, RIGHT HERE WE'LL JUST LOOK AT DNA REPLICATION.
WE'LL LOOK AT GENE EXPRESSION IN A FUTURE VIDEO TUTORIAL.
ALL RIGHTY. SO, IF WE LOOK,
LET'S--FOR NOW LET'S LOOK AT DNA REPLICATION. OKAY.
SO, EVERY PERSON STARTS LIFE AS A FERTILIZED EGG, THE ZYGOTE,
WHICH CONTAINS THE ENTIRE HUMAN GENOME.
THIS SINGLE CELL GROWS AND DIVIDES
TO BECOME A HUMAN BEING WITH ABOUT ONE TRILLION CELLS, RIGHT?
SO, HOW DOES THAT HAPPEN?
WELL, THE DNA IS GOING TO NEED TO REPLICATE.
NOW, THIS IS DEFINITELY, RIGHT, AN ANABOLIC PROCESS.
SO, WE CAN THINK OF IT AS ENDERGONIC, RIGHT?
AND THAT IT NEEDS, RIGHT,
IT'S GOING TO NEED ATP, IT NEEDS ENERGY. ALL RIGHTY.
SO, THE FIRST THING THAT NEEDS TO HAPPEN
IS WE HAVE TO UNRAVEL THIS SUPERCOIL DNA
TO EXPOSE ITS DOUBLE HELIX, RIGHT, THINK ABOUT THAT, RIGHT.
COILS UP ON THE HISTONES,
AND THEN IT COIL--LOTS OF COILING HAPPENING. ALL RIGHT.
SO, THE ENZYME HERE IS HELICASE
AND THEN OF COURSE WE NEED THE ATP--OOPS, THERE WE GO.
ALL RIGHT. AND WE RECOGNIZE, RIGHT, ASE, RIGHT,
THIS IS OUR ENZYME, AND IT HAS A VERY LOGICAL NAME,
RIGHT? WE'RE OPENING UP THE DOUBLE HELIX, SO HELICASE.
AND WE NEED ENERGY. ALL RIGHT.
SO, INTERESTINGLY, EACH OF THE TWO STRANDS GETS COPIED. OKAY.
SO, IF WE LOOK UP HERE,
WE WOULD SEE THIS AS OUR ORIGINAL STRAND,
OUR ORIGINAL DNA. ALL RIGHT.
NOW, DOWN HERE THIS WE CALL THE REPLICATION FORK,
SO WE HAVE TO SPLIT IT APART.
SO, THE HELICASE IS COMING IN
AND SPLITTING APART THE TWO STRANDS.
AND SO THERE'S THE FORK
WHERE THE REACTION STILL NEEDS TO OCCUR.
NOW, IF WE FOLLOW THESE STRANDS,
IF WE LOOK HERE WE SEE THERE'S THE THREE PRIME, WE FOLLOW IT,
WE RECOGNIZE THAT THIS IS THE PARENT STRAND.
AND SO--THEN WHAT HAPPENS IS THERE IS A SECOND ENZYME.
AND SO IF WE LOOK HERE WE SEE THIS IS THE DAUGHTER STRAND.
OKAY. SO, HERE CREATING THE DAUGHTER IS DNA POLYMERASE--
OOPS. I MESSED UP MY SPELLING. HERE WE GO.
POLYMERASE, RIGHT?
SO, ONCE AGAIN WE RECOGNIZE THAT THIS IS AN ENZYME,
AND IT'S CREATING A POLYMERIC DNA, RIGHT,
IT'S FORMING THE DAUGHTER STRAND, RIGHT?
SO, DNA POLYMERASE RIGHT,
FORMS THE DAUGHTER FROM THE PARENT.
AND THIS IS AMAZING.
THIS HAPPENS AT A RATE OF A HUNDRED NUCLEOTIDES--
WHAT DO YOU THINK? PER HOURS, PER MINUTE, PER SECOND, RIGHT?
AMAZINGLY FAST. OKAY. AND IT'S HAPPENING SIMULTANEOUSLY.
SO, IF WE LOOK OVER HERE
YOU SHOULD BE ABLE TO IDENTIFY THE PARENT
AND THE DAUGHTER STRANDS, RIGHT, SO WE CAN SEE HERE,
THIS WILL BE THE PARENT, AND THIS IS OUR DAUGHTER. OKAY.
SO, MAIN THINGS WE WANT TO KNOW ABOUT HERE ARE THE HELICASE
IS WHAT IS SEPARATING THE TWO FORKS.
DNA POLYMERASE IS FORMING THE DAUGHTER FROM THE PARENT--
DON'T WORRY ABOUT THE NUMBERS.
I JUST THINK THAT THEY ARE REALLY AMAZING.
AND THEN YOU MIGHT BE THINKING,
A HUNDRED NUCLEOTIDES PER SECOND--OH, MY GOD.
HOW DID THE--HOW MANY MISTAKES ARE MADE?
WELL, THE MISTAKES, RIGHT,
MISTAKES BASICALLY LEAD TO MUTATIONS
WHICH WE'LL TALK MORE ABOUT VERY SOON, RIGHT?
EVEN AT THIS AMAZINGLY FAST RATE
OF A HUNDRED NUCLEOTIDES PER SECOND,
THERE IS ONLY ONE MISTAKE IN 10,000.
AND THEN THE SYSTEM DOES HAVE PROOF READING.
SO, AFTER PROOF READING THE OVERALL PROCESS
IS ONLY ONE IN A BILLION MISTAKES.
SO, THANK GOODNESS FOR THAT.
IF IT WASN'T SUCH A GOOD SYSTEM,
WE PROBABLY WOULDN'T BE HERE TO TALK ABOUT IT. ALL RIGHTY.
SO, THAT CONCLUDES OUR TUTORIAL ON THE BASIC STRUCTURE OF DNA
AND HOW IT REPRODUCES TO MAKE THE DAUGHTER STRANDS
AND TO FORM THE NEW MOLECULES.
SO, PLEASE TAKE SOME TIME NOW
TO DO SOME HOMEWORK TO REINFORCE YOUR UNDERSTANDING.