[PDF] - 1 Part 1 is it to jog your memory DNA is very nearly the universal PDF Document

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1 Topic 2: A primer on the structure and function of genes Additional graphic from: http://www.accessexcellence.org http://www.eportalit.com/igx/igx.html

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2 Part 1 is it to jog your memory DNA is very nearly the universal genetic material

All hereditary information is encoded in nucleic acids
Nucleic acids are a polymer made of nucleotide monomers

RNA: some viruses DNA:

ther viruses

all other life on earth

H OH

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3 RNA compared with DNA Base pairing and Chargaff’s rule

DNA: A = T and G ≡ C RNA: A = U and G ≡ C Base pairing explains Chargaff’s rules for double stranded DNA

%A = %T and %C = %G
The ratio %G+C : %A+T varies among organisms

35% 5% 30% Strand B 35% 30% 5% Strand A C+G% G% C%

Strand symmetric Strand asymmetric

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4 Mammalian mitochondrial genome is highly strand symmetric

G rich (C poor) strand: Heavy (H) strand C rich (G poor) strand: Light (L) strand

H-strand nucleotide composition Distance from origin of replication Note: an important convention is to write out DNA in the 5’ to 3’ direction! 5’ – A T T C A G T A A – 3’ is NOT the same as 3’ – A T T C A G T A A – 5’

3’ end 5’ end 5’ end 3’ end

DNA is anti-parallel

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Transcription: In the nucleus Translation: In the cytoplasm

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7 Part 2: What is the definition of a gene?

GENE: the genetic element which is transmitted from parent to offspring during the process of reproduction that influences hereditary traits.

Beadle and Tatum (1941): one gene, one-enzyme hypothesis
one-gene, one-polypeptide hypothesis

GENE: is the segment of DNA involved in producing a polypeptide chain; it includes regions preceding and following the codon region (leader and trailer) as well as intervening sequences (introns) between individual coding segments (exons). [Note this is also the definition of a cistron.]

The traditional definitions imply that functional and structural diversity arises via local changes in the DNA sequence Important motivation for private backing of human genome sequencing

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8 Human Genome Project (HGP)and the definition of a gene

~13,000 Fruit fly ~19,000 Nematode ~30,000 Mouse ~30,000 Human Number of genes Genome

HGP:

many genes encode more than one protein
much functional divergence between humans, chimpanzee, and mice

due to changes in gene regulation (Clark et al. 2003)

We should reconsider our definition of a gene if we want to define it

according to its function

genome-function relationship is more complex than we (some) had

thought What is a gene? 1. a unit of inheritance 2. a location on a chromosome 3. a sequence of base pairs 4. a transcriptional unit 5. a determinant of phenotype They are all correct. Types of genes: 1. Protein-coding genes 2. Regulatory signal genes 3. RNA encoding genes

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A note about the definition of a gene:

In some population genetics books, alternate forms of genetic variation at a locus are called genes; i.e., allele = gene.

In this course allele ≠ gene

1. Protein coding genes. This type easily fits the modern definitions, in that

they transcribe a messenger RNA (mRNA) that is used as a template for making a polypeptide. These genes are sometimes called structural genes. We can see the problems with defining a gene as a segment of DNA involved in producing a polypeptide chain, as this differs among eukaryotes, prokaryotes and virus’s.

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DNA i Pi Plac Operator Z Y a

Structural genes Regulatory gene Promoter for lac operon Promoter for regulatory gene z = Structural gene for β-galactosidase y = Structural gene for β-galactoside permease a = Structural gene for β-galactoside transacetylase Promoter: A region of DNA extending 150-300 bp upstream from the transcription start site that contains binding sites for RNA polymerase and a number of proteins that regulate the rate of transcription of the adjacent gene. Operator: a region of DNA that indicates the starting point for reading the coding sequences of bacterial structure genes and controls the expression of those genes via interaction with a repressor.

Prokaryotic protein-coding genes are colinear with the polypeptide

OPERON: several protein coding genes that are regulated and expressed as a single unit.

RNA start DNA Introns

Exon 1 Exon 2 Exon 3

Regulatory Signals

220

+2400 Poly-A addition site

Eukaryotic protein-coding genes differ substantially from prokaryotic ones

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2. Regulatory signal genes. These are elements or motifs of DNA that are not transcribed, and serve

as signals to regulate the processing of the DNA molecule. The prominent types of such genes are:

Replicator signals: These signal the initiation or termination of DNA replication.
Telomeres: These are repeats of specific DNA sequences found at the ends of eukaryotic

chromosomes.

Segregator signals: These determine the specific sites at which the segregation machinery of the

cell attaches to the chromosomes for the process of mitosis and meiosis.

Recombination signals: The sequence element that provides a recognition site for a recombination

enzyme.

Regulator signals in prokaryotes

DNA i Pi Plac Operator Z Y a

Structural genes Regulatory gene Promoter for lac operon Promoter for regulatory gene z = Structural gene for β-galactosidase y = Structural gene for β-galactoside permease a = Structural gene for β-galactoside transacetylase Promoter: A region of DNA extending 150-300 bp upstream from the transcription start site that contains binding sites for RNA polymerase and a number of proteins that regulate the rate of transcription of the adjacent gene. Operator: a region of DNA that indicates the starting point for reading the coding sequences of bacterial structure genes and controls the expression of those genes via interaction with a repressor.

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13 Eukaryotic DNA is packaged into a structure called chromatin

Structure of chromatin can place regulatory signal genes that are dispersed in the primary DNA polymer in close proximity in 3D space.

1. Regulatory elements in primary DNA
2. Txn factor finds it’s cognate regulatory site
3. Txn factor recruits co-activators
4. co-activators open up the chromatin
5. Open chromatin allows the binding of basal txn factors
6. RNA polymerase binds to complex
7. RNA polymeraseinduced strand seperation and

begins to transcribe DNA to RNA

Regulator signals in Eukaryotes

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3. RNA encoding genes. In contrast to mRNA of protein coding genes,

the final product of the RNA gene is only transcribed RNA. RNA molecules specified by such genes fold into complex structures that USUALLY associate with proteins to form a sort of “chemical machine”. i. Transfer RNA (tRNA) ii. Ribosoaml RNA (rRNA) iii. Small nuclear RNA (snRNA) iv. Others: (snaRNA, microRNA, gRNA)

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15 Ribosomal RNA (rRNA) gene Transfer RNA (tRNA) gene

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16 Two sources for combinatorial evolution:

1. Mix and match exons for alternate splice products
2. Mix and match regulatory elements for different

patterns of gene expression

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Example of combinatory possibilities: Let’s take a look at a familiar example. Say you have a deck of 52 cards and are about to play a game a poker. You wonder how many different 5 card hands are possible. notation C(n,r) n = 52 things taken r = 5 at a time C(n,r) = n! / (n-r)!r! C(52,5) = 52! / 47! × 5! C(52,5) = 2,298,960 Now take 50 genes, each with two alternative splice products. We have (50 × 2) = 100

products. How many different possibilities if we express 10 genes at one time.

C(n,r) = n! / (n-r)!r! C(100,10) = 100! / 90! × 10! C(100,10) = 1.7 × 1013

The evolutionary dynamics of regulatory genes, and in particular combinatorial evolution, warrants serious attention

mutation is an extremely slow process
combinatorial evolution change can be achieve much more

quickly via the much faster process of recombination

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