Biology | Evolution of Genes and Genomes
L533 | 31110 | Lynch, M


BIOL 533 – EVOLUTION OF GENES AND GENOMES

Instructor: Michael Lynch, Dept. of Biology, 324c Jordan Hall,
milynch@indiana.edu.

Text: Lynch, M. 2007. The Origins of Genome Architecture. Sinauer
Assocs., Sunderland, MA.



I. A BROAD OVERVIEW – GENERAL OBSERVATIONS AND THEORY.

A. The Origin of Life.
The three major domains and the phylogenetic roots of eukaryotes
Properties of the stem eukaryote
The eukaryotic radiation
Genome repatterning and the eukaryotic big bang

B. Early Information Processing.
An early RNA world?
In vitro evolution
Evolution of the genetic code(s)

C. Genome Complexity and Organismal Complexity.
The evolution of genome size – optimal DNA content or
mutation pressure?
The small contribution from coding DNA
An overview of the human genome
Gene number and gene-family sizes
Introns and exons
Mobile genetic elements
Pseudogenes
Noncoding RNAs
The unique trajectory of human evolution
The KT boundary and mammalian evolution

D. The Theory of Gene-frequency Dynamics.
Mutation, random genetic drift, and effective population size
The neutral theory – a null model of molecular evolution
Probability of fixation
Time to fixation
Within-population polymorphism as a transient phase of evolution
Gene genealogy and the coalescent
Directional vs. balancing selection
Recombination and evolution – background selection,
selective sweeps, and genetic draft
Global effective population sizes of species
Mutation as a weak selective force


II. THEORY AND ANALYSIS OF DNA SEQUENCE EVOLUTION.

A. Analysis of Sequence Data.
Models for the evolutionary change of protein sequences
Accounting for multiple substitutions per site
Models for the evolutionary change of nucleotide sequences
Transition-transversion bias
Nucleotide usage bias
Synonymous vs. nonsynonymous substitutions
Accounting for rate heterogeneity among sites

B. Rates and Patterns of Nucleotide Substitution.
The conservative nature of molecular evolution
Silent vs. replacement substitutions
Conservative vs. radical amino-acid changes
Introns, exons, intergenic spacers, and pseudogenes
Estimation of the mutation rate from comparative sequence
data
Mutation rate and generation time
The metabolic rate hypothesis
Molecular clocks and the dating of evolutionary events
The overdispersed molecular clock
The efficiency of selection – the width of the selective sieve
The consequences of population size
The consequences of recombination
The nearly-neutral theory of molecular evolution
Expression pattern and rate of evolution
Relative rate tests

C. Polymorphisms Within Populations.
Inferences about molecular evolution from population-level
data
Tests of neutrality
Purifying selection and the mutation load
Low levels of variation in regions of low recombination
Maintenance of variation by balancing selection
Estimation of population-genetic parameters with molecular
markers
Population size and long-term growth rate
Population subdivision and migration rates
Recombination rate

D. Molecular Phylogenetics.
Methods for the reconstruction of phylogenetic trees
Using phylogenies to identify sequence sites of functional
significance
Reconstructing ancestral states
Experimental molecular evolution


III. MAJOR ISSUES IN THE EVOLUTION OF GENES AND GENOMIC ARCHITECTURE.

A. The Keys to Chromosomal Integrity
Origins of replication
Centromere
Telomeres

B. Nucleotide Composition
The molecular spectrum of mutational effects
Biased gene conversion
Evolutionary consequences of replication
Isochores
Codon usage bias

C. Mobile Genetic Elements.
Major categories and mechanisms of movement
Non-LTR retrotransposons
LTR retrotransposons
DNA-based transposons
Rates of insertion and effects on host fitness
Mechanisms of regulation of mobile element activity
Population biology of mobile elements
Positive effects of mobile-element insertions

D. The Origin of New Genes.
Gene and genome duplication
Preservational processes – subfunctionalization,
neofunctionalization, and masking effects
The evolutionary demography of duplicate genes
New gene functions from exon or domain shuffling
The case for subfunctionalization
Speciation via the divergent resolution of duplicate genes

E. Evolution of Introns.
Classification of introns
The introns-early vs. introns-late debate
Origin of the spliceosome(s)
Molecular aspects of intron size and phase
Sources of introns and spatial distribution
Exon (intron) sequence enhancers/silencers
Alternative splicing and	mRNA processing
The population biology of introns
Rates of intron gain and loss
Relevance of population size
Other forms of processed spacers
Internal excised sequences in ciliates
Inteins

F. Evolution of Transcriptional Regulation and Modular Gene
Organization.
Transcription and translation initiation
The premature translation initiation problem
Transcription termination
Operons
Spliced-leader trans-splicing
Evolution of gene subfunctions and regulatory elements
Evolution of gene networks
Small RNAs

G. Organelle Evolution.
The hybrid eukaryotic genome
Origin and evolution of the mitochondrion
Origin and evolution of chloroplasts
Organelle to nuclear genome transfer
The origin of novel genetic codes
Genome content and organization
Population biology
Inferred mutation rates and efficiency of selection
Transmission and recombination
Effective population size
Mutation pressure, Muller’s ratchet, and genome structure
Insights from other endosymbiotic genomes

H. Sex Chromosomes.
Origins
The population-genetic environment
Degeneration of the Y chromosome
Retailoring of the X

I. Genomfart
Nothing in evolution makes sense except in the light of
population genetics
The passive emergence of genome complexity by nonadaptive
processes
The frailty of adaptive hypotheses for the evolution of
organismal complexity