Recap

DNA RNA 4 bases base pairing/double helix Central Dogma of Molecular Biology

Questions for you

Which one is a longer sequence: DNA or RNA?

What does RNA do exactly?

What the difference between:transcription and translation?

Questions for you

What are the four bases of DNA?

What are the four bases of RNA?

Could you draw a detailed picture of the double helix?

DNA

Acid

Sugar A

Sugar T

Acid

Acid

Sugar G

Acid

Sugar A

Acid

SugarT

Acid

SugarA

Acid

SugarC

Acid

SugarT

DNA

Do

ub

le H

elix

More questions for you

Which bases go together?– TA– CG

Just remember T & A What does T & A stand for anyway?

– Thymine– Adenine

Recap

Structure and Function of Genes

Genetic information is stored in DNA, and the expression of this information requires several steps that flow in one direction:

Genes

Genes are segments of DNA encoding information that ultimately direct the production of RNA molecules that serve a variety of functions, including:

Genes

1. dictating the synthesis of proteins that perform a wide variety of functions in the body,

Genes

2. regulating (turning on or turning off) the expression of other genes,

Genes

3. forming structures in the cell—ribosomes—that are critical for the manufacture of proteins, and

Genes

4. transporting amino acids—the building blocks of proteins—to the ribosomes for the creation of proteins.

Human Genome Project

has confirmed that human DNA contains a little over 3 billion bases

99% of them are the same in all people In February 2001, the first major goal of the Human

Genome Project– a detailed working draft of the sequence of human DNA—

was published simultaneously in the journals

1. Nature (Lander ES et al: Nature 409:860-921, 2001) and

2. Science (Venter JC et al: Science 291:1304-1351, 2001).

Features of DNA

it offers a means of storing and coding vast amounts of information captured by the sequence of bases present in the DNA strand;

humans have about 3,000,000,000 in their genome (the complete set of genetic information);

the complementary structure allows for the faithful replication of DNA as cells divide, with one strand serving as a template for the synthesis of the other;

Features of DNA

a mechanism for preventing loss of information is built into the structure

a base that is lost or altered on one strand can be replaced using the complementary strand to direct its repair; and

the complementarity of DNA allows strands to find each other in a complex mixture of molecules;

this is termed "reannealing" or "hybridization".

Transcription

entails the synthesis of a single-stranded polynucleotide of RNA at an unwound section of DNA with one of the DNA strands serving as a template for the synthesis of the RNA.

The product of this process is called an RNA transcript, or messenger RNA (mRNA).

The result of transcription is that the genetic information encoded in DNA is transferred to RNA; this occurs in the nucleus of the cell.

Translation

follows the movement of mRNA to the cytoplasm where it interacts with structures called ribosomes to synthesize a protein.

Proteins are a linear sequence of amino acids, each of which is specified by the sequence of nucleotides in the RNA molecule

(which, in turn, was specified by the DNA where it was synthesized).

Protein Encoding

Genetic information is encoded in a sequence of three nucleotides termed codons.

The four nucleotides of RNA are adenine(A), guanine (G), cytosine(C), and uracil (U), which replaces thymine (T) in the DNA template.

These four nucleotides can be arranged in various combinations to form 64 codons,

each containing three letters (4 × 4 × 4 = 64).

Protein Encoding

Since there are 20 amino acids that nature draws on to create proteins,

there are more than enough codons in the genetic code to specify the 20 amino acids used in proteins.

Gene Structure

The number of genes in the human genome is estimated to be about 35,000, to 40,000—

considerably fewer than once thought— 80,000-100,000 But I think there really not sure yet dispersed throughout the set of

chromosomes.

Gene Structure

Although the average gene is about 3,000 bases long,

the smallest genes may be just a few hundred base pairs;

the largest is over two million base pairs in length.

Famous people named Gene

Gene Simmons Gene Kelly Gene Roddenberry Gene Hackman Gena Lee Nolin

– close enough, right?

Gene “The Hunk”

Gene Structure

Human genes, like most genes in multicellular organisms (eukaryotes), contain

introns—stretches of DNA located within the gene that are transcribed into RNA

and then spliced out before the RNA is translated into protein (see diagram).

These stretches of DNA have no discernible coding functions.

Gene Structure

However, it also appears that splicing may occur at various alternative points along the DNA molecule,

allowing for differing proteins to be constructed from what might otherwise appear to be a single "gene.“

Cool, right?

Gene Structure

Once mRNA is transcribed from a gene, it goes through several processing steps in the nucleus before being translated in the cytoplasm.

This "processing" involves: 1. the addition of a modified guanine molecule to the 5’ end

(called capping),

2. the addition of a "tail" comprised of a series of adenine bases (called a poly-A tail),

3. excision of the introns, and

4. splicing of the exons back together.

Let take a break andlook at some good genes

Gena Lee Gene “The Hunk”

Protein Sequences

Proteins are macromolecules (heteropolymers) made up from 20 different amino acids, also referred to as residues.

A certain number of residues is necessary to perform a particular biochemical function

around 40-50 residues appears to be the lower limit for a functional domain size.

Protein sizes range from this lower limit to several hundred residues in multi-functional proteins.

Protein Sequences

Amino acids The basic structure of

an a-amino acid is quite simple.

R denotes any one of the 20 possible side chains (see table).

Name3-letter code

Single code

Relative abundance(%) E.C.

MW pK VdW volume(Å3)Charged, Polar,Hydrophobic

Alanine ALA A 13.0 71   67 H

Arginine ARG R 5.3 157 12.5 148 C+

Asparagine ASN N 9.9 114   96 P

Aspartate ASP D 9.9 114 3.9 91 C-

Cysteine CYS C 1.8 103   86 P

Glutamate GLU E 10.8 128 4.3 109 C-

Glutamine GLN Q 10.8 128   114 P

Glycine GLY G 7.8 57   48 -

Histidine HIS H 0.7 137 6.0 118 P,C+

Isoleucine ILE I 4.4 113   124 H

Leucine LEU L 7.8 113   124 H

Lysine LYS K 7.0 129 10.5 135 C+

Methionine MET M 3.8 131   124 H

Phenylalanine PHE F 3.3 147   135 H

Proline PRO P 4.6 97   90 H

Serine SER S 6.0 87   73 P

Threonine THR T 4.6 101   93 P

Tryptophan TRP W 1.0 186   163 P

Tyrosine TYR Y 2.2 163 10.1 141 P

Valine VAL V 6.0 99   105 H

Protein Sequences

The polypeptide chain Two amino acids are combined in a

condensation reaction. The sequence of the different amino acids is

considered the primary structure of the peptide or protein.

Counting of residues always starts at the N-terminal end (NH2-group).

Protein Sequences

Start of the protein (NH2-group).

First residueSecond residue

Protein Sequences

Primary structure It’s the sequence of residues GLARENLQKNEDMFNPGICH Sometimes real proteins spell a lot of funny

things Like

– GIMP– WHY

Protein Sequences

Bond angles In contrast to the rather

rigid peptide bond angle (always close to 180 deg)

the bond angles phi

and psi can have a certain range of possible values

Secondary structure elements

The polypeptide chain of a protein seldom forms just a random coil.

Proteins have either a chemical (enzymes) or structural function to fulfill.

High specificity requires an intricate arrangement of 3-dimensional interactions

therefore a defined conformation of the polypeptide chain.

In fact, some neurodegenerative diseases like Huntington's may be related to random coil formation in certain proteins.

Secondary structure elements

The two most common secondary structure arrangements are

1. the right-handed a-helix and 2. the b-sheet, which can be connected into a larger tertiary

structure (or fold) – by turns and loops of a variety of types.

The b-sheets can be formed by parallel or, most common, antiparallel arrangement of individual b-strands.

Secondary structure

shows the hydrogen bonding in an actual a-helix backbone

Secondary structure

Electron density is used to show an even nicer picture.

Its hard to see But this is really an

alpha helix

Secondary structure

This is a b-sheet The chain turns then

attaches back to itself The chain can do this over

and over again Forming a woven sheet

Homework & Upcoming Stuff

Read 22-44. Project #1 will be given out next Tuesday. I’ll explain it in a second Pop-quiz is coming up.

Project #1

I’m collecting a list of the top 15 research papers in bioinformatics.

Pick a paper Read it Talk with me about it Try to understand it Summarize it in a 2 page paper with at least one

diagram and one chart/graph/table. Prepare a 20 minute PowerPoint or Visual

demonstration about the paper.

Project #1

Presentation 50% (graded 0-100) Paper 50% (graded 0-100) Presentations will start two weeks from next

Tuesday. First person to go gets +6 Second person to go get +3

Project #1

The hard part: Not only do I want a summary but I want to know The immediate impact: What exactly was made

possible through this work? Broader impact: Indirectly, how is the world a better

place because of this work? Did it lead to curing of a disease, etc.

This will take research beyond just reading the paper.

In fact, you might have to even read other cited papers.