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Diving into the gene pool: Chromosomes, genes and DNA
• DNA is the stuff that genes are
made of
• DNA contains 4 letters: A, T, G, C
• All genes are made of DNA, but not
all DNA is in genes!
Diving into the gene pool: Chromosomes, genes and DNA
• The entire DNA content of
an organism is the genome.
• The DNA is partitioned and
packaged into structures called
chromosomes. Humans have
46 chromosomes (23 pairs).
Diving into the gene pool: Chromosomes, genes and DNA
gene A
gene B
gene C
• Genes are information carriers! They encode the instructions to
make a protein. Proteins carry out the actual work of the cells.
Diving into the gene pool: From Genes to Proteins
• DNA contains four letters: A T G C
• Within a gene, these four letters are grouped into three
letter “words”. Each word codes for an amino acid (the
units that make up proteins). The combination of three
letter words codes for the sequence of a protein.
DNA
ATG - CAT - AAA
Protein
Methionine - Histidine - Lysine
Diving into the gene pool: The Central Dogma
DNA
RNA
Protein
Why a middle man?
Diving into the gene pool: The Central Dogma
gene A
DNA
* In every cell
RNA
* Only turned “on”
where needed!
Protein
* Protein is made in the
cells where it functions –
not everywhere!
The Genome: What all is in there?
6 billion ‘letters’:
2-5 % protein coding genes
25% non protein coding genes
50%+ repeated sequences
Protein coding genes
Human:
Mouse:
Fly:
Yeast:
Mustard weed:
20,000-25,000
25,000
13,000
6,100
25,700
The Genome: What all is in there?
Nature 409: 860-921
The Genome: What all is in there?
Humans share…
….99% of chimp genes
….90% of mouse genes
….61% of fly genes
….43% of worm genes
….46% of yeast genes
* So what makes us different? *
• more proteins/gene: ~22,000 genes but ~34,000 proteins
• Expansion of gene families
• The ways proteins interact and talk to one another
The Genome: What all is in there?
• Regulatory sequences
turn me off
in the brain
general “on” signal
gene A
turn me on high
in the heart!
general “off” signal
The Genome: What all is in there?
• Non-protein-coding RNA’s
• some RNA’s are active and can function in the cell on their own
• some RNA’s are incorporated into protein complexes to function
* The main functions of non-coding RNA’s are in protein
production and regulation of gene expression
The Genome: What all is in there?
• Repeat sequences
• What is typically known as ‘junk DNA’
• Why there? What does it do?
Repeated sequences shape the genome
• Can increase the size of the genome
• Often involved in chromosome translocations
• Are sometimes responsible for human disease
Repeated sequences can be useful for understanding genome
evolution, for tracking disease genes, and for forensic science
(genetic fingerprinting)
The Genome: What all is in there?
• Variation
• Single Nucleotide Polymorphisms (SNPs)
• ~1 SNP per 1300-1500 letters = 3 million differences
between two genomes; we are still 99.9% the same!
The Genome: What all is in there?
Variation
• Most SNP variation is outside genes
• Within a gene, a SNP can have one of two effects
AAG
AAA
AAC
Lysine
Lysine
Asparagine
The Genome: What all is in there?
Variation: the ApoE example
• ApoE gene contains 2 SNP’s = 3 alleles
Protein letter: 112
E2 Cysteine
E3 Cysteine
E4 Arginine
158
Cysteine
Arginine
Arginine
E4/E4 genotype: greater chance for developing Alzeheimer’s
E2/E2 genotype: “protected” from getting Alzeheimer’s
Navagating the Genome
UCSC Genome browser:
genome.ucsc.edu/cgi-bin/hgGateway
Ensemble Genome browser: www.ensembl.org/Homo_sapiens
Online Mendelian Inheritance in Man: http://www3.ncbi.nlm.nih.gov
(OMIM)