Genetics and Molecular Biology

The course aims is to provide students with a solid theoretical basis that will enable them to understand what the organization of genomes and what are the molecular mechanisms that underlie their evolution. The course aims to explore the evolutionary events that led to the current genomic and chromatin organization comparing the genomes and the chromatin architecture from the simple eukaryotes to the primates. To the modern formulation of molecular evolution have contributed the most diverse disciplines: genetics, molecular biology, genomics, mathematics, statistics, ecology etc. The study of this matter allows the student to be placed in a logical perspective and unifying many of the knowledge acquired in other courses contributing substantially to the understanding of "what a genome is and especially as it has become such." The acquisition of knowledge and understanding skills are obtained and followed through participation in lectures and teaching workshops. Ability to apply knowledge and understanding: In this area of learning, through lessons and educational workshops on the topics of the program considered most interesting, often chosen by the students, it will be possible to study the evolutionary events that led to the current genomic and chromatin organization. These evolutionary events will be investigated starting from the formation of the first cells with proto-nuclei, comparing the genomes and the chromatin architecture of species with increasing structural and functional complexity of the genome, up to the higher eukaryotes, primates and man. The ability not only to acquire knowledge and understanding, but above all to evaluate the ability to apply them appropriately, are obtained and followed by participation in lectures and educational workshops. For this purpose, moreover, laboratory activities that contribute to the development of autonomous in-depth abilities and critical skills of the acquired knowledge will take place, so that the students are able to transmit them and continue independently in their study. The evaluation consists of an oral test that aims to assess the acquired knowledge and the ability to apply it in an appropriate manner. In order to better evaluate the student's critical and in-depth abilities, presentations will be useful from recently published work on subjects covered in class. GENOME EVOLUTION LM (6CFU) (1051932) Size and Organization of Genome: - the C-value enigma; - nucleotype theory; - major components of eukaryotic genomes. Main theories to explain the C-value enigma: - constraint by mutation; - optimal DNA Effects of genome reduction - compact and hypercompact genomes; - intracellular parasites, endosymbiontes; microsporidia, nucleomorphs. Genome Organization The origin of Eukaryotes. Theories on the origin of the nucleus. Endosymbiotic theory. Eocyte hypothesis. Karyogenic model (genome compartmentalization). Encode project: the importance of the functional elements in the evolution of the control of the genomic expression. Characteristics that distinguish the DNA of eukaryotes from that of prokaryotes Reassociation kinetics. Differences in the genomic organization between eukaryotes (genes size, introns, exons, etc). Classes of repetitive DNA. –repetitive interspersed DNA. Transposable element (domestication and functionalization of TE). Gene families. Evolution of the size of the Genome: a complex multifactorial process. - minimum size of the genome of animals: insects (especially parasitic super specialized. - genome size and developmental time (smaller genomes = faster development: drosophilidi) “Hologenome theory of evolution”. Molecular and genomic evolution. The importance of the Public Data Base. Origin of new genes: - a. Small and large scale duplication; b. Lego Approach; c. Lateral gene transfer; d. ncDNA: Morpheus family, segmental duplication, chromosomal rearrangements and meiosis consequences. Positive Darwinian selection (genes involved in pathogenesis and reproduction). Asymmetry of the mutation pattern (replication and transcription). Regional variation in the rate of mutations (Haldane: X or Y-linked) Evolution of the Genomic Organization. Conservation and evolution of essential genes - Pioneering work on C. elegans and RNAi. Paralog and ortholog genes: single-copy genes and multigenic families. Genes that have a peak expression during embryogenesis show a lower number of paralogs respect to genes which are expressed in the post-embryo stage. - subfunctionalization of duplicated copies. Gene Expression: fine tuning (differences between primates). - In vertebrates: plenty of evolutionarily conserved noncoding sequences (CNC), in particular: Accelerate CNC (ANC) sequences enriched in recent segmental duplications, suggesting recent change in selective constraint following the duplication - The modular nature of gene regulation. Mechanisms of gene duplication: - gene amplification (physiologic, aberrant, genic duplication and positive selection: Morpheus Family). Dynamic mutations (mechanisms of triplet expansions) - gene conversion. Unequal crossing over. Unequal sister chromatid exchanges. Replication slipping. Role of dynamic mutations. - Mutagenic processes: - Exogenous or endogenous sources - DNA Damage Repair (DDR): Gene conversion, HR and unequal crossover, SCE, replication slippage, DNA double strand break repair pathways. - Cell cycle arrest and regulation - Triplet expansion - Human diseases correlated with dynamic mutations Evolution of replication Characteristics of the replication of eukaryotic chromatin. Chromosomal domains/Fine modulation order of gene expression; TAD, MAR, SAR Chromosome replication: - replication banding; - BrdU, gene expression and replication timing. Study of the evolution and compartimentalization of the chromatin - BrdU and the recognition of the different phases of S; - Early and late replication; - asynchrony in the replication of alleles, – fiber analysis. DNA repeats as example of genome evolution - Centromere as example of DNA and protein evolution - Centromere drive - Selfish elements of the genome Evolution of cancer genomes Chromatin organization and Morphologic banding: Chromosomes territories Brief description of the banding techniques. Comparison between the karyotypes of primates. Comparative Cytogenetics: comparison between species and within species Some hints about the importance of FISH: - studies of chromosomal rearrangements; Cen-CO-FISH; - Aneuploidy / polyploidy; - Rainbow-FISH; - Zoo-Fish; - GISH (eg, evolution of sex chromosomes); - Chromosome painting, SKY ("territoriality of the chromosomes in the nucleus); - comparative cytogenetic studies; - CGH - chromosomal painting and CGH array of related species (eg, chicken and turkey); - analysis of CNVs (Copy Number Variations in 4 major classes of dog types) Evolution of sex determination - environmental, environmental/genomic, genomic, chromosomal - Evolution of sex chromosomes

Bachelor of Science. Students must possess the basics of genetics and genomic organization, especially concerning the organization of interphase chromatin and chromosomal DNA. Prior knowledge regarding the behavior of chromosomes in meiosis and mitosis, as well as DNA mutagenesis, is required albeit these topics will be briefly reviewed in class.

Suggested readings The summary of all lectures given during the course will be available online. References of publications relevant for each class will be given as final page for each lecture. For the aforementioned topics, students are also expected to identify and read the original literature available in relevant scientific publications. The educational materials containing the synthesis of the lessons contains the bibliography with articles and reviews used for the slides given in the lessons, which should be consulted. You can view and download these articles from any computer of the university libraries. Additional readings: - Strachan & Read: Human Molecular Genetics, chapter on: "Our place in the tree of life." - B. Lewin, The Gene (Ed. Compact) the organization and evolution of genes, content and size of genomes, evolution of the Y chromosome, gene duplication and evolution, gene families, chromosomes and their organization in prokaryotes and eukaryotes.

in person

Oral exam

The course is organized in theoretical lessons, group exercises and practical components. In particular, a total of 52 teaching hours (6 CFU) are scheduled, of which 40 hours of frontal lessons (5 CFU) and 12 hours of practical exercises (1 CFU). Generally, we have weekly classes, journal clubs, roundtable discussion and team exercises for both vertical and horizontal knowledge transfer. The practical components are centered around the design of novel scientific projects pertaining to genome evolution, from presenting the original ideas to defining the experimental approach and execution of the project. The component of a chosen project will be carried out in a laboratory session generally in silico, with the entire class during the practical.

The course aims is to provide students with a solid theoretical basis that will enable them to understand what the organization of genomes and what are the molecular mechanisms that underlie their evolution. The course aims to explore the evolutionary events that led to the current genomic and chromatin organization comparing the genomes and the chromatin architecture from the simple eukaryotes to the primates. To the modern formulation of molecular evolution have contributed the most diverse disciplines: genetics, molecular biology, genomics, mathematics, statistics, ecology etc. The study of this matter allows the student to be placed in a logical perspective and unifying many of the knowledge acquired in other courses contributing substantially to the understanding of "what a genome is and especially as it has become such." The acquisition of knowledge and understanding skills are obtained and followed through participation in lectures and teaching workshops. Ability to apply knowledge and understanding: In this area of learning, through lessons and educational workshops on the topics of the program considered most interesting, often chosen by the students, it will be possible to study the evolutionary events that led to the current genomic and chromatin organization. These evolutionary events will be investigated starting from the formation of the first cells with proto-nuclei, comparing the genomes and the chromatin architecture of species with increasing structural and functional complexity of the genome, up to the higher eukaryotes, primates and man. The ability not only to acquire knowledge and understanding, but above all to evaluate the ability to apply them appropriately, are obtained and followed by participation in lectures and educational workshops. For this purpose, moreover, laboratory activities that contribute to the development of autonomous in-depth abilities and critical skills of the acquired knowledge will take place, so that the students are able to transmit them and continue independently in their study. The evaluation consists of an oral test that aims to assess the acquired knowledge and the ability to apply it in an appropriate manner. In order to better evaluate the student's critical and in-depth abilities, presentations will be useful from recently published work on subjects covered in class. GENOME EVOLUTION LM (6CFU) (1051932) Size and Organization of Genome: - the C-value enigma; - nucleotype theory; - major components of eukaryotic genomes. Main theories to explain the C-value enigma: - constraint by mutation; - optimal DNA Effects of genome reduction - compact and hypercompact genomes; - intracellular parasites, endosymbiontes; microsporidia, nucleomorphs. Genome Organization The origin of Eukaryotes. Theories on the origin of the nucleus. Endosymbiotic theory. Eocyte hypothesis. Karyogenic model (genome compartmentalization). Encode project: the importance of the functional elements in the evolution of the control of the genomic expression. Characteristics that distinguish the DNA of eukaryotes from that of prokaryotes Reassociation kinetics. Differences in the genomic organization between eukaryotes (genes size, introns, exons, etc). Classes of repetitive DNA. –repetitive interspersed DNA. Transposable element (domestication and functionalization of TE). Gene families. Evolution of the size of the Genome: a complex multifactorial process. - minimum size of the genome of animals: insects (especially parasitic super specialized. - genome size and developmental time (smaller genomes = faster development: drosophilidi) “Hologenome theory of evolution”. Molecular and genomic evolution. The importance of the Public Data Base. Origin of new genes: - a. Small and large scale duplication; b. Lego Approach; c. Lateral gene transfer; d. ncDNA: Morpheus family, segmental duplication, chromosomal rearrangements and meiosis consequences. Positive Darwinian selection (genes involved in pathogenesis and reproduction). Asymmetry of the mutation pattern (replication and transcription). Regional variation in the rate of mutations (Haldane: X or Y-linked) Evolution of the Genomic Organization. Conservation and evolution of essential genes - Pioneering work on C. elegans and RNAi. Paralog and ortholog genes: single-copy genes and multigenic families. Genes that have a peak expression during embryogenesis show a lower number of paralogs respect to genes which are expressed in the post-embryo stage. - subfunctionalization of duplicated copies. Gene Expression: fine tuning (differences between primates). - In vertebrates: plenty of evolutionarily conserved noncoding sequences (CNC), in particular: Accelerate CNC (ANC) sequences enriched in recent segmental duplications, suggesting recent change in selective constraint following the duplication - The modular nature of gene regulation. Mechanisms of gene duplication: - gene amplification (physiologic, aberrant, genic duplication and positive selection: Morpheus Family). Dynamic mutations (mechanisms of triplet expansions) - gene conversion. Unequal crossing over. Unequal sister chromatid exchanges. Replication slipping. Role of dynamic mutations. - Mutagenic processes: - Exogenous or endogenous sources - DNA Damage Repair (DDR): Gene conversion, HR and unequal crossover, SCE, replication slippage, DNA double strand break repair pathways. - Cell cycle arrest and regulation - Triplet expansion - Human diseases correlated with dynamic mutations Evolution of replication Characteristics of the replication of eukaryotic chromatin. Chromosomal domains/Fine modulation order of gene expression; TAD, MAR, SAR Chromosome replication: - replication banding; - BrdU, gene expression and replication timing. Study of the evolution and compartimentalization of the chromatin - BrdU and the recognition of the different phases of S; - Early and late replication; - asynchrony in the replication of alleles, – fiber analysis. DNA repeats as example of genome evolution - Centromere as example of DNA and protein evolution - Centromere drive - Selfish elements of the genome Evolution of cancer genomes Chromatin organization and Morphologic banding: Chromosomes territories Brief description of the banding techniques. Comparison between the karyotypes of primates. Comparative Cytogenetics: comparison between species and within species Some hints about the importance of FISH: - studies of chromosomal rearrangements; Cen-CO-FISH; - Aneuploidy / polyploidy; - Rainbow-FISH; - Zoo-Fish; - GISH (eg, evolution of sex chromosomes); - Chromosome painting, SKY ("territoriality of the chromosomes in the nucleus); - comparative cytogenetic studies; - CGH - chromosomal painting and CGH array of related species (eg, chicken and turkey); - analysis of CNVs (Copy Number Variations in 4 major classes of dog types) Evolution of sex determination - environmental, environmental/genomic, genomic, chromosomal - Evolution of sex chromosomes

Bachelor of Science. Students must possess the basics of genetics and genomic organization, especially concerning the organization of interphase chromatin and chromosomal DNA. Prior knowledge regarding the behavior of chromosomes in meiosis and mitosis, as well as DNA mutagenesis, is required albeit these topics will be briefly reviewed in class.

Suggested readings The summary of all lectures given during the course will be available online. References of publications relevant for each class will be given as final page for each lecture. For the aforementioned topics, students are also expected to identify and read the original literature available in relevant scientific publications. The educational materials containing the synthesis of the lessons contains the bibliography with articles and reviews used for the slides given in the lessons, which should be consulted. You can view and download these articles from any computer of the university libraries. Additional readings: - Strachan & Read: Human Molecular Genetics, chapter on: "Our place in the tree of life." - B. Lewin, The Gene (Ed. Compact) the organization and evolution of genes, content and size of genomes, evolution of the Y chromosome, gene duplication and evolution, gene families, chromosomes and their organization in prokaryotes and eukaryotes.

in person

Oral exam

The course is organized in theoretical lessons, group exercises and practical components. In particular, a total of 52 teaching hours (6 CFU) are scheduled, of which 40 hours of frontal lessons (5 CFU) and 12 hours of practical exercises (1 CFU). Generally, we have weekly classes, journal clubs, roundtable discussion and team exercises for both vertical and horizontal knowledge transfer. The practical components are centered around the design of novel scientific projects pertaining to genome evolution, from presenting the original ideas to defining the experimental approach and execution of the project. The component of a chosen project will be carried out in a laboratory session generally in silico, with the entire class during the practical.