Molecular Biology Primer. CptS 580, Computational Genomics, Spring 09

Transcription

1 Molecular Biology Primer pts 580, omputational enomics, Spring 09

2 Starting 19 th century What do we know of cellular biology? ell as a fundamental building block 1850s+: ``DNA was discovered by Friedrich Miescher and his pupil Richard Altmann Mendel s experiments with garden pea plants Laws of inheritance, ``Alleles, ``genotype vs. ``Phenotype 1909: Wilhelm Johannsen coined the word ``gene Still.. Proteins were thought to be the primary genetic materials but..

3 Avery s Experiment

4 What does a gene produce? ene?... Protein

5 DNA: Birth of Molecular Biology (1953) J.D.Watson F. Lab, ambridge M.H.F.Wilkins R. s ollege, London

6 DNA: A Double Helix Phosphate roup Sugar Nitrogenous Base 5 A T 3 A,,,T Adenine ytosine uanine Thymine omplementary Base Pairing Rule: A T 3D helix A T T A Reverse omplement: 5 3 AAT TTA 3 5 Strand#1 3 5 Strand#2

7 entral Dogma: DNA -> RNA -> Protein

8 Spot the difference! DNA RNA Phosphate roup Sugar Nitrogenous Base 5 A T 3 A,,,T Adenine ytosine uanine Thymine Phosphate roup Sugar Nitrogenous Base A A,,,UAdenine ytosine uanine Uracil A T A Strand#1 3 T A 5 Strand#2 U Single Stranded RNA types: trna mrna rrna

9 Proteins Like a DNA and a RNA molecule is a chain of nucleotides {A,,,T/U}, a protein molecule is a ``chain of amino acids (aka, peptide chain) There are 20 amino acids Next question: How does a gene encode the information to produce a protein molecule?

10 enetic ode: Khorana, Holley and Nirenberg, 1968 ombinatorial Logic: 4 2 < 20 < 4 3 Hence 3 nucleotides in a codon

11 A little convention for convenience Let us use a straight line from now on to represent a DNA strand (or equivalently, its sequence) Top strand or Watson strand Bottom strand or rick strand

12 Information Flow During Protein Synthesis ene DNA 3 5 e 5 1 e 2 e 3 e 4 e 5 3 Transcription One gene can code for mrna e 1 e 2 e 4 many proteins! (alternative + trna Translation splicing in eukaryotes) Protein oding (exons) Non-oding (introns) Stable Structure Folding Nuclear genome

13 Several Questions Leading Up to Today s omputational Biology and Bioinformatics What are the nucleotides in a DNA molecule? (problem of sequencing) What DNAs make up the genome of a species? (problem of genome sequencing, genome assembly) What are the genes within a genome? (gene identification/discovery) What protein and RNA products does a gene produce? (annotation) What is the native 3D structure of a protein and how does it get there? (protein folding, structure prediction) Similar questions can be asked of RNAs too.

14 Several Questions. Are there non-protein coding genes? (pseudo-genes) Under what conditions does a gene express itself, and are there genes that are more active than others under experimental conditions? (gene expression analysis, microarrays) Are there a subset of genes that co-operate, and does a gene s activity get affected by others? (gene regulatory networks) How do genes look and behave in closely related species? What distinguishes them? (gene and species evolution) What is the ``TREE OF LIFE? (phylogenetic tree reconstruction) How does a protein know where to go next within a cellular complex? (localization, signal peptide prediction) AND MANY MORE.

15 omputational Biology & Bioinformatics: Problem Areas Function Sequence Discovery enome ene Regulatory elements RNA products Proteins ene to protein annotation ene expression analysis Microarray experiments RNA interference Metabolic networks/pathway DNA Structure ene structure prediction RNA structure prediction Protein structure prediction Evolutionary Studies Tree of life Speciation Population enetics Haplotype analysis Nucleotide polymorphism

16 Where are we now? enbank An annotated collection of all publicly available nucleotide and amino acid sequences. As of October 2005, the NBI s public collection contained: bases, and 60.3 million sequences, obtained from over 165,000 organisms Source: NBI enbank

17 UniprotKB/Swiss-Prot A knowledge base for protein sequences. ontains annotated protein sequences ontains 201,594 sequences, 73,123,101 amino acids. Source:

18 omputational Biology and Bioinformatics A rapidly evolving field Technology biological and computational apabilities oncepts Knowledge and Science A plethora of grand challenge questions An Ante-disciplinary Science? An interesting read: ``Antedisciplinary Science, Sean R. Eddy, PLoS omputational Biology, 1(1):e6

19 Referred Slide Materials, Acknowledgments, and Web Resources ``DNA From the Beginning ( Dolan DNA Learning enter, old Spring Harbor Laboratory Stanford University, S 262: omputational enomics Wikipedia (DNA, gene, genetics) J.D. Watson, The Double Helix: A personal account of the discovery of the structure of DNA