Prepared with lots of help from friends... Metsada Pasmanik-Chor, Zohar Yakhini and NUMEROUS WEB RESOURCES. BioInformatics / Computational Biology Introduction & Biological Terms.

A Few Basic Concepts of Molecular Biology: Genetic material - DNA & RNA. DNA is a sequence of bases (A,C,T,G). Watson-Crick–ery. Proteins. The central dogma of molecular biology. Bio-Informatics Tools Freely available on the web: Highlights. Outline

One chromosome, (sometimes circular). Prokaryotes vs. Eukaryotes

Cell Size and Shape m All organisms are made of cells - basic unit of life (10 14 cells in the human body; metabolism, replication). Cells in all organisms have same type ofgenetic material.

The Eukaryotic Cell cytoskeleton: * In plants: chloroplast & cell wall.

Each human cell contains 23 pairs of chromosomes. Chromosomes can be distinguished by size and by unique banding patterns. This set is from a male, since it contains a Y chromosome. Females have two X chromosomes. DNA - the Genetic Material

Different genes are activated in different cells, creating the specific proteins that give a particular cell type its character. Different Eukaryotic Cell Types

Example: Tissues in Stomach Cells originate from one embrio cell and have identical DNA. Different cell types: Metabolism, regulation, function.

control region gene - coding region CONTROL REGIONS - Usually are adjacent to genes. Determine when expressed, to what extend. “JUNK DNA” - Unknown function. DNA Structure centromere telomere

Source: Alberts et al DNA is made of 4 subunits (nucleotides). Each nucleotide contains: sugar, phosphate group and a base. DNA - (deoxyribonucleic acid - THE Double Helix)

Sugar A T C G deoxyribose ribose Nucleotide 4 DNA bases Purines Pyrimidines (RNA) (DNA)

Conclusion: DNA strands are complementary (1953). Watson-Crick Complementarity Human Sheep Turtle Sea urchin Wheat E. coli DNA source % of each base Purines/ Pyrimidines Base ratios Purines Pyrimidines

A binds to T C binds to G AATGCTTAGTC TTACGAATCAG Perfect match AATGCGTAGTC TTACGAATCAG One base mismatch Watson-Crick Complementarity

Genes carry the instructions for cellular proteins. Variations in the code is the source for cellular variations. Disease and susceptibility to disease can be caused by changes in the DNA (mutations). DNA is identical in all cells of an individual, almost identical among different individuals of same species (99.9%), and very similar in related species (human vs chimpanzee - 98% identity). Only 3% of cellular DNA has a known function !  Variability - facts Human individuality

Hereditary mutations: Carried in the DNA of the reproductive cells. The mutation will be present in all of the offspring's body cells. Acquired mutations: Developed in the DNA during a person's lifetime. If the mutation arises in a body cell, copies of the mutation will exist only in descendants of that particular cell.

RNA is very similar to DNA but has: Only one strand. Ribose as a sugar. Uracil (U) instead of Thymine (T). RNA - ribonucleic acid Some viruses store genetic information in form of RNA. In eukaryotes, RNA is formed from DNA in a process called transcription where elimination of introns  (splicing) occurs 

splicing Chromosomal DNA Splicing - RNA Synthesis and Processing mRNA mrna.gif Mature mRNA Poly A tail introns Transcription by RNA polymerase exons The seven green loops stand for introns The eight blue bands stand for exons Promoter/enhancer exons Stop signal Gene introns splicing

Splicing - RNA Synthesis and Processing

Example of Alternative Splicing

Used in translation: tRNA - Small RNA, serves as “adaptor” between mRNA and amino acids. rRNA - One of the structural components of the ribosome (the translation machine from mRNA to proteins). Types of RNA mRNA - A copy of a gene (without introns), encoding protein sequence. See animation at:

Genes can be turned ON and OFF

Transcription Factors

 nitiation  of  ranscription  by  olymerase

Regulation of Expression promoter

nucleus cytoplasm

The Genetic Code: From 4 3 = 64 Codons to 20 AA. 5’3’ 4 nucleotide types 20 amino acids 3 letter code 64 Codons

The Genetic Code: From 4 3 = 64 Codons to 20 AA.

The Genetic Code The only start amino acid is Methionine, which has a single codon.

Amino Acid Relative Frequencies- Mammals

5’ ACGTGTAGTTGCCGTGACG 3’ 3’ TGCACATCAACGGCACTGC 5’ A DNA sequence with direction shown N C N PKRGACMLTNQFKRKSACQ C A protein sequence with ends indicated Nucleotides vs Amino Acids Code

Proteins

Translation - Mediated by the ribosome, an organ which is made from rRNA and proteins.

Proteins are Made of Amino Acids

Translation in Eukaryotes Animation:

Protein Structure

What Determines Cell Structure and Function ? Unique protein expression by each cell type. Proteins are ~60% of dry mass of living cell. Proteins determine function. How is this controlled ?

Levels of Eukaryotic Gene Regulation

Central Dogma Transcription mRNA Cells express different subset of the genes in different tissues and under different conditions. Gene (DNA) Translation Protein DNA RNA Protein Symptomes (Phenotype )

The Central Dogma of Molecular Biology Replication- DNA duplication Transcription- RNA synthesis Nucleus Cytoplasm Translation- Protein synthesis

New Central Dogma… 1 gene Many protein types Many mRNA Transcripts due to alternative splicing

1 gene Many mRNA transcripts Many protein types Central Dogma in the 21 st Century.