Gene clusters are formed by duplication and divergence Sequence divergence is the basis for the evolutionary clock Pseudogenes are dead ends of evolution Unequal crossing-over rearranges gene clusters Genes for rRNA form tandem repeats ( The repeated genes for rRNA maintain constant sequence) Crossover fixation could maintain identical repeats Satellite DNAs often lie in heterochromatin Arthropod satellites have very short identical repeats Mammalian satellites consist of hierarchical repeats Minisatellites are useful for genetic mapping

2.1 Introduction We can think about mapping genes and genomes at several levels of resolution: A genetic (or linkage) map identifies the distance between mutations in terms of recombination frequencies. A linkage map can also be constructed by measuring recombination between sites in genomic DNA

DNA是遗传物质 DNA为双螺旋 DNA的复制是半保留的 通过碱基配对进行核酸杂交 突变改变了DNA的序列 突变集中于热点 顺反子是单个DNA片断 多重等位基因的种类

分子生物学 Molecular Biology Zhao WANG (王钊), M.D./Pharm.D. School of Life Science Tsinghua University

29.1 Introduction 29.2 Fly development uses a cascade of transcription factors 29.3 A gradient must be converted into discrete compartments 29.4 Maternal gene products establish gradients in early embryogenesis 29.5 Anterior development uses localized gene regulators

28.1 Introduction 28.2 Transforming viruses carry oncogenes 28.3 Early genes of DNA transforming viruses have multifunction oncogenes 28.4 Retroviruses activate or incorporate cellular genes 28.5 Retroviral oncogenes have cellular counterparts 28.6 Ras oncogenes can be detected in a transfection assay 28.7 Ras proto-oncogenes can be activated by mutation at specific positions 28.8 Nondefective retroviruses activate proto-oncogenes 28.9 Proto-oncogenes can be activated by translocation 28.10 The Philadelphia translocation generates a new oncogene 28.11 Oncogenes code for components of signal transduction cascades 28.12 Growth factor receptor kinases can be mutated to oncogenes 28.13 Src is the prototype for the proto-oncogenic cytoplasmic tyrosine kinases 28.14 Oncoproteins may regulate gene expression 28.15 RB is a tumor suppressor that controls the cell cycle 28.16 Tumor suppressor p53 suppresses growth or triggers apoptosis

26.1 Introduction 26.2 Carriers and channels form water soluble paths through the membrane 26.3 Ion channels are selective 26.4 Neurotransmitters control channel activity 26.5 G proteins may activate or inhibit target proteins 26.6 G proteins function by dissociation of the trimer 26.7 Growth factor receptors are protein kinases 26.8 Receptors are activated by dimerization 26.9 Receptor kinases activate signal transduction pathways

25.1 Introduction 25.2 Oligosaccharides are added to proteins in the ER and Golgi 25.3 The Golgi stacks are polarized 25.4 Coated vesicles transport both exported and imported proteins 25.5 Different types of coated vesicles exist in each pathway 25.6 Cisternal progression occurs more slowly than vesicle movement 25.7 Vesicles can bud and fuse with membranes 25.8 SNAREs control targeting 25.9 The synapse is a model system for exocytosis 25.10 Protein localization depends on specific signals 25.11 ER proteins are retrieved from the Golgi 25.12 Brefeldin A reveals retrograde transport 25.13 Receptors recycle via endocytosis 25.14 Internalization signals are short and contain tyrosine

24.1 Introduction 24.2 Clonal selection amplifies lymphocytes that respond to individual antigens 24.3 Immunoglobulin genes are assembled from their parts in lymphocytes 24.4 Light chains are assembled by a single recombination 24.5 Heavy chains are assembled by two recombinations 24.6 Recombination generates extensive diversity 24.7 Avian immunoglobulins are assembled from pseudogenes 24.8 Immune recombination uses two types of consensus sequence 24.9 Recombination generates deletions or inversions 24.10 The RAG proteins catalyze breakage and reunion 24.11 Allelic exclusion is triggered by productive rearrangement 24.12 DNA recombination causes class switching 24.13 Early heavy chain expression can be changed by RNA processing 24.14 Somatic mutation generates additional diversity 24.15 B cell development and memory 24.16 T-cell receptors are related to immunoglobulins 24.17 The major histocompatibility locus codes for many genes of the immune system

14.1 Introduction 14.2 Breakage and reunion involves heteroduplex DNA 14.3 Double-strand breaks initiate recombination 14.4 Double-strand breaks initiate snapsis 14.5 Bacterial recombination involves single-strand assimilation 14.6 Gene conversion accounts for interallelic recombination 14.7 Topological manipulation of DNA 14.8 Specialized recombination involves breakage and reunion at specific sites 14.9 Repair systems correct damage to DNA 14.10 Excision repair systems in E. coli 14.11 Controlling the direction of mismatch repair 14.12 Retrieval systems in E. coli 14.13 RecA triggers the SOS system 14.14 Eukaryotic repair systems