1. Structures and Functions of Nucleic Acids

2. Organization and Content of Genomes

3. DNA Replication

4. The Mutability and Repair of DNA

5. DNA Recombination

6. Transcription and RNA Processing

7. Translation

8. Regulation of Gene Expression

9. Techniques of Molecular Genetics

Introduction to

Molecular Genetics

http://priede.bf.lu.lv/ Studiju materiāli / MolekularasBiologijas / Ievads MolGen / EN

http://priede.bf.lu.lv/ Studiju materiāli / MolekularasBiologijas / Ievads MolGen / EN

GENOME the complete haploid set of an organism’s DNA

(or the whole genetic information of an organism) divided: physically – into CHROMOSOMES

functionally – into GENES and other elements

CHROMOSOMEa discrete unit of the genome carrying single DNA molecule that contains many genes

GENEa segment of DNA specifying a protein or

noncoding (nc) RNA

DNAthe molecule that encodes genetic

information in all cells[many viruses store the genetic information in the RNA

molecule]

Prokaryotes typically have one chromosome

Eukaryotes always have many chromosomes

Molecular Biology of the Gene, 5th Edition

The chromosome content of the HUMAN GENOME

Eukaryotic organelles also contain genetic information

Genomes, 2nd Edition

Genome size and gene number roughly correlate with organism’s complexity

(modified)

Viral genomes are in many forms

A map of the HIV genome

Bacterial genomes are almost entirely composed of genes

~ 0.2% (9000 bp) of the E. coli chromosome

Genome of E. coli

Mitochondria have cut-down versions of bacterial genomes

The Human mitochondrial genome: (i) Respiratory complex genes (ii) Ribosomal RNA genes (iii) Transfer

RNA genes

Gene density is decreased in more complex organisms

Molecular Biology of the Gene, 6th Edition

The organization of genes on a human chromosome

The sequence content of the HUMAN GENOME

Prokaryotic DNA is floating in cytoplasm Eukaryotic DNA is located within nucleus

Molecular Cell Biology, 4th Edition

In nucleus, DNA is associated with proteins: CHROMATIN

Proteins:• Histones - H1, H2A, H2B, H3, H4• Nonhistone proteins

Chromosomes exist in distinct states during different phases of the cell cycle

Molecular Biology of the Gene, 5th Edition

Chromosomes exist in distinct states during different phases of the cell cycle

Chromosomes have a hierarchic organization

Life The Science of Biology, 7th Edition

Molecular Biology of the Gene, 5th Edition

The different forms of interphase chromatin

NUCLEOSOME is the basic unit of eukaryotic chromosome structure

Molecular Biology of the Gene, 5th Edition

NUCLEOSOME = 2x H2A, H2B, H3, H4 + DNA

Histones are small, basic proteins that share a common structural motif -

HISTONE FOLD

Molecular Biology of the Gene, 5th Edition

Molecular Biology of the Gene, 5th Edition

Histone folds bind to each other mediating THE ASSEMBLY OF

NUCLEOSOMES

Higher order chromatin structure: 10-nm fiber is packed into 30-nm fiber

6-fold compacting 40-fold compacting

Molecular Biology of the Gene, 5th Edition

Linker histone H1 and tails of the core histones act to form the 30-nm fiber

Molecular Biology of the Gene, 6th Edition

Further compaction involves large loops of 30-nm fiber

1000-fold compacting

Molecular Biology of the Gene, 5th Edition

Interphase chromosomes are ‘fluid’ - REGULATION of chromatin structure

Structure and positioning of nucleosomes is determined by non-histone proteins

Types of changes in chromatin during transcription initiation

Histone modifications alter the ‘meaning’ of chromatin

Recombinant DNA, 3rd Edition

Specific meanings of the histone modifications: HISTONE CODE

There are two types of interphase chromatin

1. Euchromatin– the ‘usual ‘ form– contains (potentially) active genes

2. Heterochromatin– more condensed form– additional proteins (HP1)

– constitutive• no genes• feature of all cells• e.g., centromeric, telomeric DNA

– facultative• in some cells some of the time• inactive genes

Molecular Biology of the Cell, 5th Edition

Mitotic chromosomes are formed from chromatin in its most condensed form

Each chromosome has a characteristic banding pattern

Each eukaryotic chromosome has one centromere, two telomeres and many origins of replication (ori)

Molecular Biology of the Gene, 5th Edition