91399 - EVOLUZIONE DEL GENOMA

Learning outcomes

The aim of this course is to provide advanced knowledge about the structure and evolution of prokaryotic and eukaryotic genomes. The course will take into consideration the origin of the genetic code, the origin of eukaryotes, the elements that characterize genomes and the molecular mechanisms underlying their evolution, and will deal with the concepts of function and complexity. Moreover, a consistent section of the course is dedicated to the discussion of the principal evolutionary models and the contribution of selection, genetic drift, mutation rate, recombination, robustness, and canalization in different groups of organisms. Each student have the opportunity to present recent publications in the field of evolutionary genomics, and discuss them with the class.

Course contents

1. Introduction

General information about the course: logistics, structure, program, materials. Introduction to genomics: timeline, the Human Genome Project, overview of human genome, the ENCODE project.

2. Evolution by DNA Duplication

 Evolution by gene duplication. Types and mechanisms of DNA duplication. Molecular homology. Gene duplication and gene families. Origin and evolution of duplicated genes: divergent evolution, nonfunctionalization, retaining of the original function, neofunctionalization, subfunctionalization. Concerted evolution. Birth-and-death evolution: expansion and contraction of gene families. Case studies: vertebrate olfactory receptors and primeate opsines. Poluploidy: polyploidization, autopolyploidy, allopolyploidy, consequences of polyploidy, diploidization. Whole genome duplication.

3. Evolution by Molecular Tinkering

Exaptation, evolution by tinkering. Protein domains. Orthology and domain shuffling. Internal gene duplications. Exon-domain correspondence. Case study: antifreeze proteins in fishes. Mosaic proteins. Exon shuffling. Gene fusion and fission. Domain accretion. Multidomain gene assembly. Alternative splicing. De novo origin of genes. Nested and interleaved genes. Gene loss. Molecular tinkering: suboptimality and gratuitous complexity.

4. Mobile Elements in Evolution

Mobile elements, transposable elements and transposition. Classification of transposable elements. DNA-mediated transposable elements. Retroelements. LINEs and SINEs. Retrosequences. The “ecology” of transposable elements. Genetic and evolutionary effects of transposition. Transposition and speciation. Horizontal gene transfer. Intracellular DNA transfer.

5. Patterns of Molecular Evolution

Molecular evolution, mutations, point mutations in coding sequences, noisy synonymous mutations, segmental mutations. Eukaryotic gene structure. Substitution rate, substitutions in coding sequences, dN/dS (Ka/Ks), causes of variation in substitution rates, variation among gene regions, variation among genes. Relaxed selection. Types of amino acid substitution, patterns of amino acid substitution. Causes of variation in substitution rates across different lineages. "Living fossils". Origin and evolution of the genetic code: stereochemical hypothesis, coevolution hypothesis (or metabolic hypothesis), error-minimization hypothesis. Codon bias, wobble pairing and isoacceptor tRNAs. Selection on codon bias.

6. Inferring Evolutionary Processes from DNA Sequence Data

Alleles in a population, mutation, selection and fitness, selection coefficient, molecular population genetics. Models of molecular evolution. Hardy-Weinberg Equilibrium. Random sampling, genetic drift, Wright-Fisher population, Wright-Fisher model of genetic drift, population size, census population size, effective population size, factors reducing the effective population size. Fisher's theorem, fitness landscape. Direct vs linked selection, linkage disequilibrium, hitchhiking and selective sweeps, hard sweeps and soft sweeps, background selection. Epistasis. The mechanisms of evolution: mutationist hypotheses, neutralist hypotheses, selectionist hypotheses. The neutral theory of molecular evolution, the value of the neutral theory as a null model. Misunderstandings and misuse of the neutral theory. The nearly-neutral theory. Discussions and controversies about the neutral theory. Genomics approaches to detect natural selection.

7. Reticulate Evolution and the Origin of Eukaryotes

The “tree of life” hypothesis. Tree vs network. The Forest of Life, the Ring of Life. The vertical and horizontal components of prokaryote evolution. The origin of eukaryotes: archezoa hypothesis, hydrogen hypothesis, the "fateful encounter" hypothesis. The progenitors of eukaryotes. Origin of introns.

8. Mitonuclear Evolution

Mitochondria. ATP production by chemiosmosis. Prokaryote complexity limits, surface/volume ratio and cell size limits, phagocytosis, "the energetics of genome complexity". The mitochondrial genome, endosymbiotic gene transfer. Genomic conflicts: multilevel selection, replication advantage, segregation advantage, conflicts between cytoplasmic and nuclear genes. Mito-nuclear coevolution. Why mitochondria have genomes? The CoRR hypothesis. The mitochondial theory of ageing and the division of labour hypothesis. Mitochondrial bottleneck, selection, drift. The Mother's Curse.

9. Case studies

Flipped classroom, group discussion.

Readings/Bibliography

• Parts 2-6, 7: Dan Graur “Molecular and Genome Evolution”, Sinauer Associates (Main text).

• Part 6: Matthew Hahn “Molecular Population Genetics”, Sinauer Associates, Oxford University Press; Glenn-Peter Sætre and Mark Ravinet “Evolutionary Genetics: Concepts, Analysis, and Practice”, Oxford University Press.

• Part 8: Geoffrey Hill “Mitonuclear Ecology”, Oxford University Press. 

• Scientific publications and online material.

Teaching methods

The first part of the course consists of classic frontal teaching, and it will introduce concepts, mechanisms, and methods of analysis.

The second part is carried out in "flipped classroom" mode, and its purpose is to delve into some case-studies and discuss state-of-the-art works. Each student choose a scientific publication dealing with the topics introduced in the first part of the course, and presents it to the class. A discussion will follow, in which the teacher acts as the moderator.

Before taking this course, it is highly recommended to have attended the following courses:
91360 - Genetica di Popolazione ed Evoluzione Molecolare
91789 - Evoluzione e Filogenesi (C.I.).

Assessment methods

The final exam consists of a simulation of the scientific publication process.
Each student will write a review paper (in english) about a topic of their choice, and submit it to the teacher that will act as an Editor and will send the manuscript to two reviewers (other students in the class). The reviewers will send their reviews to the teacher that will add his own comments and will send everything back to the author that will revise the manuscript. The revised manuscript will be submitted to the teacher that will proceed with a final evaluation.
The peer-review process will be subject to evaluation as well, and each student will have to review 2 papers.

The final score will be calculated as follows:

• Peer review: 0-4 points per paper (max 8 points);
• Writing and revision of the review paper: 0-18 points;
• Brief final interview: 0-4 points.

Detailed informations about the evaluation process will be given during the introductory lesson.

Teaching tools

Slides, scientific publications, online multimedia.

Office hours

See the website of Fabrizio Ghiselli