93266 - Molecular and Genome Evolution

Learning outcomes

This course explores how evolution occurs on a molecular scale. The student will acquire a basic understanding of the mechanisms by which genes and their products change over time, of the effects of such changes on genome evolution, and of the analyses needed to use DNA sequences to trace evolutionary history and processes. The course will cover the fundamental concepts of evolutionary biology through both classical studies and discussion of recent primary literature.

Course contents

0. Introduction
General information about the course: logistics, structure, program, materials.


1. Evolution 101
The foundations of evolutionary theory. Standing genetic variation and molecular evolution. Classification of mutations: point mutations, point mutations in coding sequences, noisy synonymous mutations, segmental mutations. Recombination, gene conversion, unequal crossing-over, inversion, slippage. Survivorship bias. Single Nucleotide Polymorphisms (SNPs). Estimating the mutation rate, mutation rates are a compromise, is mutation random? Mutation biases, DNA replication errors, Male-driven evolution. Substitutions, rate of substitution, causes of variation in substitution rates.


2. Selection
Population, locus, allele, haplotype. Variation, fitness, selection, mutation and selection, types of selection, allele frequencies. Hardy-Weinberg equilibrium. Changes in allele frequencies, assortative/disassortative mating. Selection coefficient. Codominant selection, dominant selection, recessive selection, allele frequency equilibrium and selection, dominant deleterious alleles, recessive deleterious alleles, overdominance, balancing selection, sickle cell anemia and malaria, underdominance, disruptive selection, frequency-dependent selection, sexual selection and sexually selected traits. Limits of natural selection: genetic constraints, pleiotropy, multilocus selection, additive fitness, non-additive fitness (epistasis), epistatic interactions, historical constraints, ontogenetic constraints. The problem of stasis in evolution, “living fossils”. The paradox of sex, long-term advantages of sex and recombination. Direct vs linked selection. Linkage disequilibrium, genetic hitchhiking, selective sweeps, hard sweeps vs soft sweeps, background selection.


3. Drift
Chance and necessity. Unexpected genetic variation. Genetic load. The neutral theory of molecular evolution. Random sampling, Wright-Fisher population, Wright-Fisher model of genetic drift, random genetic drift, neutrality, population size, effective population size, factors that reduce effective population size. Rate of gene substitution, fixation probability, fixation time. Mutational meltdown. The nearly-neutral theory. Discussions and controversies about the neutral theory. Fisher’s theorem. The fitness landscape. Misunderstandings and misuse of the neutral theory.


4. Inferring evolutionary processes from DNA sequence data
The value of the neutral theory as a null model. The molecular clock. Measures of variability: segregating sites, heterozygosity, P-distance, nucleotide diversity. The coalescent theory and the expected pattern of sequence variation: the coalescent, coalescent theory, time to coalescence. Population mutation rate (θ), nucleotide diversity (π), and segregating sites. Tajima’s D test, natural selection and the sign of Tajima’s D, demographic changes and the sign of Tajima’s D, interpretation of Tajima’s D. Descriptive statistics for sequence divergence between populations. The Hudson-Kreitman-Aguadé (HKA) test, interpretation of the HKA test. Rates of substitution in protein-coding sequences, synonymous vs nonsynonymous rates. Detecting selection using divergence. dN/dS (Ka/Ks), general guidelines to interpret dN/dS, distribution of values of dN/dS. Notes on dN: patterns of amino acid replacement. Notes on dS: noisy synonymous mutations. The McDonald-Kreitman test and its extensions, the Neutrality Index, Direction of Selection. Genome scans, sliding windows.


5. Genome evolution
Genome size and number of genes. Evolution of prokaryotic genomes: genome size in prokaryotes, genomescapes and evolutionary regimes, the operon, horizontal gene transfer, the prokaryotic mobilome, Muller’s ratchet, mutational meltdown, horizontal gene transfer and the evolution of prokaryotes, pangenomes, genome size variability, gene loss, genome miniaturization, the minimal gene set, non-orthologous gene displacement, protein functions encoded in the minimal gene set, the bureaucracy ceiling hypothesis of genome complexity, the principal forces of evolution in prokaryotes. Evolution of eukaryotic genomes: the concept of function, an evolutionary classification of genomic function, detecting functionality at the genomic level, C value, genome size, mutations that increase or decrease genome size, transposable elements and genome size, complexity, C-value paradox, hypotheses for genome size evolution, selectionist hypotheses, the onion test, genetic load, nucleotypic hypotheses, phenotypic effects of genome size, neutralist hypotheses, the selfish DNA hypothesis, the mutational hazard hypothesis, effective population size and genome evolution, non-adaptive hypotheses of genome evolution, the G-value paradox, exaptation, evolution as tinkering, suboptimality and gratuitous complexity, irremediable complexity by constructive neutral evolution.


6. Species
Species. Phenotypic clustering, morphological species concept, problems with the morphological species concept. Biological species concept, supporting evidence, hybridization. Problems with the biological species concept: does interbreeding within a species maintain cohesion? Does reproductive isolation keep species apart? The genetic cluster species concept. The phylogenetic species concept. Conflicting phylogenies, incomplete lineage sorting. Which definition of species? Evolution of barriers to gene flow: prezygotic and postzygotic barriers. Developmental incompatibilities in hybrids: the Bateson-Dobzhansky-Muller model. Haldane’s rule. Modes of speciation: allopatric speciation, peripatric speciation, parapatric speciation, sympatric speciation. Polyploidy: autopolyploidy, allopolyploidy, evolutionary consequences of polyploidy.


7. Homology
Homology vs homoplasy. Homologous structures. Convergent adaptation. Alignment establishes homology. Types of molecular homology: orthology and paralogy. Gene families. The ortholog conjecture.


8. Reconstructing the past
Taxonomy. Tree thinking. Phylogenetic trees. Character state definitions: plesiomorphy, apomorphy, symplesiomorphy, autapomorphy, synapomorphy. Phylogenetic reconstruction. Monophily, paraphily, polyphily. Tree root, unrooted and rooted trees. Multiple hits and the saturation problem. Building trees: distance methods, Unweighted pair group method with arithmetic means (UPGMA), neighbor joining (NJ), character-based methods, maximum parsimony (MP), maximum likelihood (ML), bootstrapping, Bayesian inference (BI).

Readings/Bibliography

• Glenn-Peter Sætre and Mark Ravinet “Evolutionary Genetics: Concepts, Analysis, and Practice”, Oxford University Press.
  

• Lindell Bromham “An Introduction to Molecular Evolution and Phylogenetics” (Second Edition), Oxford University Press.
  

• Lindell Bromham "Origins of Biodiversity: an introduction to macroevolution and macroecology", Oxford University Press.

• Scientific Articles

Teaching methods

Frontal lectures, group discussion of case-studies, flipped classroom.

Assessment methods

Oral examination

Teaching tools

Slides, scientific publications, online multimedia.

Office hours

See the website of Fabrizio Ghiselli