Lecture 1

© Garland Science 2008

THE UNIVERSAL FEATURES OF CELLS ON EARTH

What is it to be alive?

Even when surrounded by friends, we are all

alone.

Lecture 1

Life is encapsulated

All Cells Are Enclosed in a Plasma Membrane Across Which Nutrients and Waste Materials

Must Pass

If you want something done right,

You better do it yourself.

All Cells Function as Biochemical Factories Dealing with the Same Basic

Molecular Building Blocks

“Are we slaves to our own DNA?”

Lecture 1

All Cells Store Their Hereditary Information in the Same Linear

Chemical Code (DNA)

DNA STRUCTURE & FUNCTION

• A DNA Molecule Consists of Two Complementary Chains of Nucleotides

• The Structure of DNA Provides a Mechanism for Heredity

Chapter 1

Lecture 1All Cells Replicate Their

Hereditary Information by Templated Polymerization

Lecture 1

All Cells Use Proteins as Catalysts

Lecture 1The Fragment of Genetic Information Corresponding to One Protein is One

Gene

Intron>5kbIntron ~2kb

Promoter

Exon 1 Exon 2 Exon 3

Intron~5kb

Promoter Protein Coding Sequence

Intron ~20 bp

Terminator

Prokaryotic Gene

Eukaryotic Gene

Lecture 1All Cells Transcribe Genes intothe Same Intermediary Form (RNA)

Lecture 1All Cells Translate RNA intoProtein in the Same Way

So, who’s wrong?

Both!

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The Sequencing of GenomesOne of the most profound technological

accomplishments in human history is the sequencing of the human genome…

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GENOMESOne of the major differences between prokaryotes and

eukaryotes in the size/complexity of their genomes.

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Prokaryotes have “concise genomes”

Lecture 1The human genome seems to contain a huge amount of “junk

DNA”

Genetic information evolves by changing sequences

Mutation – a change in the nucleotide sequence of the genetic material of an organism – is the underlying force of evolution.

• Mistakes during replication

• Chemical Changes in the nucleic acids

• UV – dimerization

• Spontaneous decomposition – base changes

• Chemical/physical changes at the chromosome level

• Radiation (X-ray/Gamma) – double-strand breaks

• Sexual reproduction (polyploidy)

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Some genes are highly conserved

More than 200 gene families are common to all life.

Most of these “orthologous genes”

are essential.

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Some genes evolve rapidly

But how do they do this when most mutations tend to mess

things up more than they improve them?

They must find a way to break free from the

oppression of natural selection

Lecture 1New genes are generatedfrom pre-existing genes

Duplication events Retroviruses

Horizontal Gene Transfer - genes can be transferred between organisms both in the laboratory, and in nature.

Gene duplications give rise to Families of related genes that are

“free” to evolve for a while.hCYP3A LocusChromosome-7

43cDNA

3A43 3A4

4cDNA

P23A7

7cDNA

P1

5cDNA

40 Kb

3A5

4 Kb 5 Kb

~80% Homology

Gellner et al., 2001Finta & Zaphiropoulos, 2000

All have roughly 90% homology in the first 1000 bp of their promoters.

Irreducible complexity

Lecture 1

Pseudogenes are evidence

Eukaryotes often have pseudogenes, duplicated genes that have accrued mutations that render them inactive, in their genomes.Mutated regulatory elements, frame shifts, addition/loss of stop codons, lost splice sites, deleterious mutations, etc.

What else can we do by knowing the sequence of our, and other

animals genomes?

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Geneticists can explore evolutionary relationships

among species by comparing orthologous genetic

sequences

Conoidea based on 12S Ribosomal RNA

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CladisticsWe make assumptions when we do this…

• Evolution is real - members of a group share a common evolutionary history, and are "closely related," more so to members of the same group than to other organisms.

• Bifurcation - new kinds of organisms may arise when existing species or populations divide into exactly two groups.

• Organisms change over time – closely-related groups are share synapomorphies, unique features not present in more distant ancestors

And even more when we use gene sequences…• Mutations are a “one-way” street• We can assign a “value” for every base-pair mutated• “horizontal gene transfer” has not occurred among the

orthologues.

Lecture 1

Data Mining!The identification and characterization of gene orthologues helps us in ever expanding ways:

1. Enhanced discovery• By finding regions that are highly conserved, primers can

be designed to discover orthologues from new species2. Accelerated science

• We can compare gene sequences and hint at their function, expression patterns, etc.

3. More powerful experiments• We can plan methods to genetically engineer just about

anything4. GAAATAACA and Pharmacogenomics

• We can peer into our own genomes and predict certain diseases and the success of many treatments