| M W F; 10:10 - 11:00 pm |
Molecular Biology |
Douglas W. Smith |
| York 2722 |
BIMM 100 |
5254 Muir Biology Building |
| Fall, 2000 |
x42620; dsmith@ucsd.edu |
| BIMM100 | Syllabus
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Readings: Brown, 14: 368 - 388
Outline:
Genomes change via Mutation and Recombination
But ... how can one learn about the past? and how evolution has
taken place?
One has only the present ... plus some paleobiology evidence
Answer: genome comparisons
Also: Origin of Life or Origin of Genomes
A. Origin of Genomes: RNA World
Beginnings of the first precellular Genomes: Self-replicating Polynucleotides
Primary argument favoring an
Initial catalytic World of Self-Replicating Polynucleotides:
1. Polynucleotides can self-replicate if enzymes are present to
increase rates ...
2. Ribozymes are catalytic Polynucleotides ...
Ribozymes: self-cleavage (Class
I introns); RNase (RNase P); peptidyl transferase
... plus other lab-induced activities ...
RNA World: ... [Brown, Fig
14.2]
Envision an inaccurate copying plus template-binding process,
thereby generating many different polynucleotide sequences,
some of which eventually had catalytic activity including self-replication,
becoming more sophisticated and accurate ... RNA ProtoGenomes
DNA Genomes:
probably Protein Catalysts developed
from Ribozymes prior to DNA genomes ...
why? ... not clear ...
1) larger alphabet (20 amino acids vs 4 nucleotides) => greater
variety of primary sequence
2) physical flexibility? ... polypeptides are more flexible in
3D space than polynucleotides ...
But why peptide bonds? (see Box 14.1: peptide nucleic
acid ...)
Why these specific 20 amino acids, i.e. these specific 20 R groups
???
Are these uniquely important for some reason for "life"
???
Two hypotheses for source of Protein catalysts:
... [Brown, Fig 14.3]
1) RNA both was enzyme (Ribozyme) AND encoded a Polypeptide
2) RNA encoded a second Coding Molecule which in turn encoded
a Polypeptide
Problem: RNA molecules are not good Coding Molecules due to instability of the ribo-phosphodiester bond (reactivity of the 2'-OH)
Solution: reduce the 2'-OH => DNA coding molecules... [Brown, Fig 14.4]
Double-stranded DNA: obvious solutions to Replication and Repair, as well as Recombination ...
B. Genetic Diversity: Gene Duplication
Evolution of Life:
14000 million years ... Big
Bang formation of Universe ... [Brown, Fig 14.1]
4600 million years ... Solar System
3500 million years ... first Cells
1400 million years ... first
eukaryotes ... [Brown, Fig 14.5]
640 million years ... first multicellular animals
530 million years ... Cambrian Revolution ... proliferation
of Invertebrates
500 million years ... massive Extinction
350 million years ... terrestrial insects, animals, plants
...
208 million years ... Triassic ... age of Dinosaurs
65 million years ... Cretaceous: mass extinction of Dinosaurs
4.5 million years ... Primates and humans
0.150 million years ... Eve: Out of Africa
Genome Complexity: mainly due to two dramatic
increases in number of genes
1) prokaryotes: ~1000-5000 genes ... 3500 - 1400 million
years
2) simple eukaryotes: ~ 10000 - 25000 genes ... 1400 -
500 million years
3) vertebrates: ~ 50000 genes ... 500 - 0 million years
Three Main Ways to Acquire
New Genes:
1) Gene Duplication,
followed by Mutation and selection of New Gene functions
2) Protein Domain Rearrangement - rearrange existing genes
3) Acquire new Genes from Other Species
1. Gene Duplication:
the dominant mechanism
...
although Horizontal Gene Transfer may be more important than heretofore
realized ...
Mechanisms:
1) duplication of entire
Genome
2) duplication of whole Chromosome or large parts thereof
3) duplication of individual Genes
a. Duplication of Entire
Genome - AutoPolyploidy ... [Brown, Fig 14.6]
Duplication due to
nonseparation of Gametes during Anaphase I in meiosis ...
Get: gametes with 2n chromosomes
Organisms with 2n chromosomes in gametes now are 4n in diploid
cells ...
Their gametes with 2n chroms
can NOT interbreed with original 1n gametes !!
This leads to 3n chroms,
which segregate improperly during Anaphase I, aborting meiosis
... [Brown, Fig 14.7]
This is the definition of Speciation!!! ... now have a new Species, one that cannot interbreed with the parental or source Species ...
AutoPolyploidy also increases
the number of Genes in the new Species ...
With duplicate genes, the duplicated gene is now under
no selective pressure to retain the original function (function
supplied by first gene) and hence can evolve into gene encoding
new function ...
Examples of Genome Duplications:
Yeast ... some 100 million years ago
... [Brown, Research Brief 14.1]
Synteny (same relative position) of Paralog genes found
in Chromosomes VII and XVI ...
Totality of Duplicated Regions constitute about 50% of the current
genome !!! ... thus, the genome had duplicated itself ...
Probably true in other genomes as well ...
b. Duplication of Single,
Whole Chromosome or large part thereof ...
Generally not viable
... or leads to Disease State, e.g. Trisomy 21: mongolism ...
Probably due to imbalance between genes whose products interact ...
c. Duplication of Individual
Genes and Groups of Genes ...
Occurs relatively often
during evolutionary time ...
Example: human globin gene families ... [Brown, Fig 14.8]
Mechanisms for Gene Duplication
- Recombination between Repeats:
1) Unequal Crossing-Over ... [Brown, Fig 14.9A]
2) Unequal Sister Chromatid Exchange ... [Brown, Fig 14.9B]
3) DNA amplification:
recombination during replication in bacteria ... [Brown, Fig
14.9C]
Fate of Duplicate Gene:
1) Pseudogene - acquires
mutations to inactivate original function, no new function
2) New Gene - acquires mutations and eventually encodes
protein with new catalytic function ...
Example: globins
Concerted Evolution
Groups of genes which,
when duplicated, retain their original function
Example: ribosomal RNA genes ...
probably due to a Selective Advantage to cells in which
all such duplicated genes retain their original function ... for
example, such can grow more rapidly if protein synthesis is rate-limiting
to growth, since they would have more ribosomes ...
2. Protein Domain Rearrangements
Domains in Proteins: ...
[Brown, Fig 14.11]
segment of the polypeptide
chain, often that of a common structure or function
Two Mechanisms for Rearrangements:
1) Domain Duplication ... [Brown, Fig 14.12A]
2) Domain Shuffling ... [Brown, Fig 14.12B]
Examples:
1) Collagen - duplication
of short gene domain encoding Gly-X-Y ... [Brown, Fig 14.13]
2) Domain Shuffling in Tissue Plasminogen Activator ... [Brown,
Fig 14.14]
The latter is a good example
of 4 protein domains, each encoded by different gene Exon ...
This correlation of one Exon - one Domain holds true
occasionally but not very often ...
3. New Genes Acquired from Other Species ...
a. Horizontal Gene Transfer
Many possible mechanisms:
phage or viruses; transposable elements; broad host-range plasmids;
direct DNA uptake; direct cell fusion; bacterial conjugation (interacting
bridge between 'male' and 'female' bacteria, permitting plasmid
transfer, eg F-factor)
b. AlloPolyPloidy
Interbreeding between different
Plant Species ... new flower types ...
Species are closely related species ...
C. Genetic Diversity: NonCoding
DNA
Same Recombination
and Mutation Mechanisms as for Coding DNA for DNA Duplications
...
1. Origins of Introns
Two major Hypotheses:
1) Introns 'early': introns are ancient and are being lost
in eukaryotes ...
Most likely true for Group I and II ribozyme introns ...
2) Introns 'late': introns evolved recently and are accumulating
in eukaryotes ...
Introns early hypothesis includes the Exon theory
of Genes ... [Brown, Fig 14.17]
Exons evolved from early short genes that encoded polypeptides
that formed a multisubunit protein ...
Prediction: exons encode Protein Domains ... by and large: not true ... inconclusive ...
Prediction: homologous genes in different organisms
should have similar Intron structure ...
True in some organisms and genes, not true for others ... inconclusive
...
Also does not explain absense of Exons in prokaryotes ... this favors Introns 'late' ...
2. Human DNA
Human DNA most similar to that
of chimpanzee: 1.5% different ...
Speciation: some 4.5-5.0 million years ago ...
Possible human ancestor species ... [Brown, Fig 14.20]
Differences with chimpanzee
DNA:
1) several gene duplications ...
2) much divergence of noncoding DNA ...
3) few rearrangements, eg Chromosome 2 ...[Brown, Fig 14.21]
| BIMM100 | Syllabus
| Sections / Off Hrs | Grading
Policy | DNASYSTEM
|
| Lectures | Journal
Articles | Study Qs | Lab
Techniques | Exams |
If you have problems or comments, send email to Doug
Smith