introduction to molecular biology, genetics and genomics references: lecture 1
TRANSCRIPT
Introduction to Molecular Biology, Genetics and
Genomics
References: www.biostat.wisc.edu/
Lecture 1
Overview
Molecular biology crash course: The different parts of a cell DNA, RNA, chromosomes, nucleus, cytoplasm Bio-chemical entities of a cell: mRNA, proteins genes, heredity, transcription, translation, gene
regulation, gene expression, alternative splicing
Life Two categories:
Prokaryotes (e.g. bacteria) Unicellular No nucleus
Eukaryotes (e.g. fungi, plant, animal) Unicellular or multicellular Has nucleus
Prokaryote vs. Eukaryote
Eukaryote has many membrane-bounded compartment inside the cell Different biological processes occur at different
cellular location
Organization of biological information
Organism
Tissue
Chromosome
Cell
http://publications.nigms.nih.gov/thenewgenetics/chapter1.html
Chemical contents of cell
Water Macromolecules (polymers) - “strings” made by
linking monomers from a specified set (alphabet)
ProteinDNARNA…
Small moleculesSugarIons (Na+, Ka+, Ca2+, Cl- ,…)Hormone…
The central dogma of Molecular biology
DNA
RNA
Proteins
Transcription
Translation
image from the DOE Human Genome Programhttp://www.ornl.gov/hgmis
DNA Short for Deoxyribonucleic acid
composed of small chemical units called nucleotides (or bases) adenine (A), cytosine (C), guanine (G) and
thymine (T) ATGC is the alphabet
DNA is double stranded: made up two twisting strands
Each strand of DNA is a string composed of the four letters: A, C, G, T
Nucleotides A nucleotide has 3 components
Sugar ring (ribose in RNA, deoxyribose in DNA) Phosphoric acid Nitrogen base
Adenine (A) Guanine (G) Cytosine (C) Thymine (T) or Uracil (U)
Polymerization: Nucleotides => nucleic acids
Phosphate
Sugar
Nitrogen Base
Phosphate
Sugar
Nitrogen Base
Phosphate
Sugar
Nitrogen Base
G
A
G
T
C
A
G
C
5’-AGCGACTG-3’
AGCGACTG
Phosphate
Sugar
Base
1
23
4
5
Often recorded from 5’ to 3’, which is the direction of many biological processes.e.g. DNA replication, transcription, etc.
5’
3’
DNA
Free phosphat
e
5 prime 3 prime
DNA is a double helical molecule
DNA molecules consist of two strands arranged in a double helix
DNA is made up of nucleotides
Double-helical structure is needed for the DNA molecule to store and pass with great precision
James Watson, Francis Crick, Maurice Wilkins and Rosalind Franklin
Watson-Crick Base Pairs
A always bonds to T C alwaysbonds to G
This is called base pairing.A and G are double ringed structures called purines.C and T single ringed structures called pyrimidines
5’ and 3’ of a DNA molecule• The backbone of this molecule has
alternating carbon and phosphate molecules
each strand of DNA has a “direction” at one end, the terminal carbon
atom in the backbone is the 5’ carbon atom of the terminal sugar
at the other end, the terminal carbon atom is the 3’ carbon atom of the terminal sugar
therefore we can talk about the 5’ and the 3’ ends of a DNA strand
DNA double helix
G-C pair is stronger than A-T pair
DNA stores the blue print of an organism
The heredity molecule
Has the information needed to make an organism
Base pairing enables self-replication: one strand has all the information
Chromosomes All the DNA of an organism is
divided up into individual chromosomes
prokaryotes (single-celled organisms lacking nuclei) typically have a single circular chromosome
eukaryotes (organisms with nuclei) have a species-specific number of chromosomes
Image from www.genome.gov
Different organisms have different numbers of chromosomes
Organism # of chromosomes
Yeast 32
Human 46
Fly 8
Mouse 40
Arabidopsis 10
Worm 12
Human Chromosomes
Genes
genes are the basic units of heredity
a gene is a sequence of bases which specifies a protein or RNA genes
the human genome comprises ~ 25,000 protein-coding genes (still being revised)
One gene can have many functions
One function can require many genes
…GTATGTCTAAGCCTGAATTCAGTCTGCTTTAAACGGCTTC…
Structure of genes
DNA
GeneNon-coding Promoter
Gene A Gene B Gene C
Genomes
Refers to the complete complement of DNA for a given species
the human genome consists of 2X23 chromosomes
every cell (except egg and sperm cells and mature red blood cells) contains the complete genome of an organism
Some Greatest Hits
Some Genome Sizes
Number of sequenced genomes
The central dogma of Molecular biology
DNA
RNA
Proteins
Transcription
Translation
RNA
RNA is like DNA except: single stranded U is used in place of T
a strand of RNA can be thought of as a string composed of the four letters: A, C, G, U
Transcription
In eukaryotes: happens inside the nucleus
RNA polymerase is an enzyme that builds an RNA strand from a gene
RNA Pol II is recruited at specific parts of the genome in a condition-specific way.
Transcription factor proteins are assigned the job of Pol II recruitment.
RNA that is transcribed from a gene is called messenger RNA (mRNA)
Transcription: Process of turning DNA into RNA
mRNA
The central dogma of Molecular biology
DNA
RNA
Proteins
Transcription
Translation
Translation
Process of turning mRNA into proteins.
Happens inside the cytoplasm in ribosomes
ribosomesare the machines that synthesize proteins from mRNA
Translation process reads one codon at a time
translation begins with the start codon
translation ends with the stop codon
Translation happens in ribosomes
Codons
Each triplet of bases is called codon How many codons are possible? Each codon is responsible for coding a
particular amino acid.
The Genetic Code
Proteins
Protein is the actual “worker” for almost all processes in the cell
Proteins are long strings ofcomposed of amino acids
There are 20 different amino acids known
The structure of a protein is intimately connected to its function
Protein: a polymer of amino acids
Amino Acids
Proteins are the workhorses of the cell
structural support storage of amino acids transport of other substances coordination of an organism’s activities response of cell to chemical stimuli movement protection against disease selective acceleration of chemical reactions
Proteins are complex molecules
Primary amino acid sequence
Secondary structure Tertiary structure Quaternary
structure
Some well-known proteins
Hemoglobin: carries oxygen
Insulin: metabolism of sugar
Actin: maintenance of cell structure
Hemoglobin protein HBA1
>gi|224589807:226679-227520 Homo sapiens chromosome 16, GRCh37.p9 Primary Assembly
1 CCCACAGACTCAGAGAGAACCCACCATGGTGCTGTCTCCTGACGACAAGACCAACGTCAA
61 GGCCGCCTGGGGTAAGGTCGGCGCGCACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGAG
121 GATGTTCCTGTCCTTCCCCACCACCAAGACCTACTTCCCGCACTTCGACCTGAGCCACGG
181 CTCTGCCCAGGTTAAGGGCCACGGCAAGAAGGTGGCCGACGCGCTGACCAACGCCGTGGC
241 GCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCGCACAAGCT
301 TCGGGTGGACCCGGTCAACTTCAAGCTCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGC
361 CCACCTCCCCGCCGAGTTCACCCCTGCGGTGCACGCCTCCCTGGACAAGTTCCTGGCTTC
421 TGTGAGCACCGTGCTGACCTCCAAATACCGTTAAGCTGGAGCCTCGGTGGCCATGCTTCT
481 TGCCCCTTTGG
DNA sequence (491 bp)
>sp|P69905|HBA_HUMAN Hemoglobin subunit alpha OS=Homo sapiens GN=HBA1 PE=1 SV=2MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR
Amino acid sequence (142 aa)Protein 3d structure
Examples of proteins
RNA Processing in Eukaryotes
eukaryotes are organisms that have enclosed nuclei in their cells
in many eukaryotes,RNAs consist of alternating exon/intron segments
exons are the coding parts
introns are spliced out before translation
RNA Splicing
RNA Genes
not all genes encode proteins for some genes the end product is RNA
ribosomal RNA (rRNA), which includes major constituents of ribosomes
transfer RNAs (tRNAs), which carry amino acids to ribosomes
micro RNAs (miRNAs), which play an important regulatory role in various plants and animals
lincRNAs (long non-coding RNAs), play important regulatory roles.
Central Dogma revisited
DNA
RNA
Proteins
Transcription
Translation
ncRNA, miRNA, rRNAs
Non-coding RNA processing
Summary Key concepts in molecular biology
Central Dogma DNA, RNA, proteins Chromosomes, Nucleus, Ribosomes
Important processes Transcription Translation RNA splicing