What was the first replicating molecule?

? What was the first self-replicating (hereditary) molecule? Proteins, DNA and RNA are all potential candidates as a hereditary molecule DNA is the universal hereditary molecule (now) But, this was not discovered until 30 yrs after chemical evolution theory proposed so no bias towards DNA in trying to figure out which molecule became a hereditary molecule

What does it mean to be a “hereditary molecule?” When a cell reproduces, it makes an identical copy of itself. There must be some “message” the original cell gives to the new cell to ensure it is identical: Makes same proteins,same structure, same energy source, same metabolism, etc. That message is the “hereditary molecule”. The hereditary molecule makes a copy of itself before the cell divides into two. The copy goes into the new cell.

What are the criteria for a hereditary molecule? 1. A hereditary molecule must contain information Instructions for the new cell as to: what proteins to make and how they should interact which will in-turn instruct the cell as to how to grow, how to get and utilize energy, how to respond to the environment, how to reproduce, in essence- how to be a cell

DNA? 1. A hereditary molecule must contain information Yes! DNA contains information within it’s nucleotides that tells the cell what RNA molecule to make If DNA in cell has sequence: AATCA, that provides info to the cell to make RNA molecule with sequence UUAGA, which then provides instructions for a protein A--T G--C

RNA? 1. A hereditary molecule must contain information Yes! RNA contains information within it’s nucleotides that tells the cell what amino acids to assemble to together in a chain which results in a protein If RNA molecule in cell is AAG CCA, that provides info to cell to start building a chain with lysine and proline

NO! You do NOT need to know these!

Protein? 1. A hereditary molecule must contain information Not quite as obvious as with DNA and RNA b/c think of protein as being at the end of the code. But, does a protein’s sequence give you info about what it does- YES! The sequence of amino acids dictates, what the protein will do.

+ ATGCT ATGCT TACGA ATGCT TACGA TACGA TACGA ATGCT What are the criteria for a hereditary molecule? 2. A hereditary molecule must be able to be copied (act as a “template”) The instructions are a code that can be copied Free nucleotides in cell Example: DNA A G ATGCT TACGA ATGCT C ATGCT TACGA T + TACGA TACGA ATGCT

DNA and RNA? 2. A hereditary molecule must be able to be copied (act as a “template”) DNA and RNA? Yes! The rules of complementary base pairing make it easy for the cell to copy DNA and RNA

Protein? 2. A hereditary molecule must be able to be copied (act as a “template”) Protein? No! There is no code for replicating proteins (nothing analogous to the complementary base pairing of DNA and RNA) The only way for your cell to get more of a protein is to replicate the hereditary molecule that codes for it.

What are the criteria for a hereditary molecule? 3. Be able to catalyze reactions When a molecule is copied (criteria 2), a lot of reactions occur in that process: breaking of bonds, formation of new bonds as the new molecule is created (as in previous slide diagram). DNA Polymerase Catalyzes DNA replication Life on earth today: cells have specialized enzymes (proteins) to do this. But as life was evolving, these would not have been around so the hereditary molecule itself would have had to replicate itself.

This means the molecule must be structurally complex 3. Be able to catalyze reactions Molecules that catalyze reactions must be able to bind to the the substrate at multiple locations Must also be very specific for that substrate so not catalyzing unwanted reactions. This means the molecule must be structurally complex and variable! Actual DNA Polymerase Model

Proteins? 3. Be able to catalyze reactions Absolutely! One of the most important kinds of proteins for the cell are ENZYMES Enzymes are the primary molecules that can catalyze reactions in cells But, too bad for proteins b/c they lost the “can it be copied?” game, which leaves…

DNA? 3. Be able to catalyze reactions Images representing different Proteins Diagrams representing different DNA molecules Versus *It doesn’t matter what the DNA sequence is, result is a double helix

+ + + + + ? + X X Who’s in the lead? DNA RNA Protein Contain information Template Catalyze Reactions + + X + ? + X

RNA? 3. Be able to catalyze reactions Basic structure of an RNA molecule called a ribozyme Recall RNA molecule structure is more varied than DNA (attributed to the extra OH on the sugar)

Yes! RNA? 3. Be able to catalyze reactions Some controversy over whether or not RNA molecules truly catalyze their OWN replication However, This was the first solid evidence for the “RNA world hypothesis”: stating that RNA was the first self-replicating molecule!

DNA, RNA and Protein

DNA RNA All 20 trillion cells in your body have the same DNA How do DNA, RNA and Protein Play Together? All 20 trillion cells in your body have the same DNA This is referred to as your “genome” Humans have about 3 billion base pairs (G-C) in their genome What do those letters (chemicals) do? base pair The cell reads the sequence of letters and builds a RNA molecule based on what information is provided by the DNA DNA RNA

DNA RNA “Transcription” How does the cell read DNA to make RNA? The transcription machinery of the cell knows the complementary base-pairing rule:If it reads a “G”, it places a “C” in the growing RNA molecule A T G G U A C C

RNA Protein “Translation” What is the new RNA molecule used for? Different machinery (proteins) in the cell now read the RNA and the sequence of bases provides information about which amino acids to put together RNA Protein “Translation”

There are 4 different bases and 20 different amino acids, how does this work? 3 RNA bases = 1 amino acid If RNA is C C G then Cell Adds a Proline (Pro) to the Chain

From DNA to Protein

RNA Amino Acids Protein So if you have 3 BILLION bases in your genome, do your cells just make one gigantic protein that is 1 billion amino acids? NO! The DNA in the genome is divided up into genes Gene: A sequence of DNA that encodes for a protein Black Regions: Genes Blue Regions: DNA that doesn’t encode for a protein RNA Amino Acids Protein

The amino acid chain grows until all RNA for that gene is read then it folds into the right conformation

= Gene Regulation If all 20 trillion cells have the same DNA and all of that DNA together codes for some 100,000 proteins….do ALL of your cells make all of those 100,000 proteins? For example: Red Genes encode proteins that play a role in muscle contraction Those genes will only be transcribed to RNA and translated to protein IN MUSCLE CELLS Yellow genes encode proteins that play a role in memory Those genes will only be transcribed and translated in brain cells = Gene Regulation