Exploring Molecular Evolution Using Bioinformatics to infer evolutionary relationships
DNA is the molecule of life! DNA has the same structure in all organisms. Your DNA is like the DNA of a jellyfish, a fungi or a tree! The DNA you have determines what you will look like and sometimes behave like!
DNA DNA is made up of two strands (shown here in blue and red). The strands are held together by nitrogen bases (shown here in yellow) There are four nitrogen bases: Cytosine, Guanine, Adenine and Thymine What pairs with C? What pairs with A? http://www.tokyo-med.ac.jp/genet/picts/dna.jpg http://academy.d20.co.edu/kadets/lundberg/dnapic2.html
The order of the nitrogen bases within DNA is important! • DNA is arranged on structures called chromosomes. • Segments of this DNA, genes, are coding regions. • The code is found in the order of the nitrogen bases; G, T, A and C. This genetic code is read 3 bases at a time. • Each gene is a ‘recipe’ for making a protein. Source: Chromosome: http://academy.d20.co.edu/kadets/lundberg/dnapic2.html
Proteins in you! 1. Amylase 5. Red blood cells contain the protein haemoglobin. 2. Two proteins for muscle movement – actin and myosin And a protein connecting muscle fibres – dystrophin. 3. Another protein found in muscle is myoglobin. 6. Collagen – a tough and flexible protein. 4. Keratin
The human genome:the ‘recipe book’ for making a human • You have 2m of DNA in each body cell. This amounts to ~ 3.1 billion base pairs! • The human genome consists of approximately 30 thousand genes. • Each gene is around 30 thousand bases long. • The longest gene at 2.4 million bases – codes for dystrophin. 60% of this is used to code for protein. It takes your body 16 hrs to read the gene and produce the protein! • A short gene at 500 bases - codes for insulin. • The rest of your DNA (over 3 billion bases) is known as junk DNA!
Mapping genomes (the recipe books) • 1995 First bacteria - Haemophilus influenzae • 1996 First unicellular eukaryotic – Yeast • 1998 First multicellular - C. elegans (a nematode worm) • 2000 Drosophila melanogaster (fruit fly) and Arabidopsis thaliana (plant) • 2001 Human - Homo sapiens • 2002 Mouse - Mus musculus • 2005 Chimpanzee - Pan troglodytes • Current: working on many including tammar wallaby some genomes and their sizes
Where would the Amoeba genome go in the table below? The largest known genome belongs to a microscopic amoeba, Amoeba Dubia (670 000 Mb), which is closely followed in size by the lungfish and the Easter lily. Which goes to show that size isn't everything! Genome size does not correlate with evolutionary status!
Compare your genetic code with… 61% like a fruit fly! 99% like a mouse! a chimp? Each other? Source: Mouse http://animals.timduru.org/dirlist/mouse/mouse.jpg Drosophila: http://www.innate.se/drosophila.jpg Chimpanzee: http://www.utalii.com/Hotels/images/Chimpanzee.jpg
The protein, amylase Active Site Active Site Active Site Barley Pig Human
The protein, haemoglobin Fish Goose Human Worm Pig
Looking at beta-globin A human beta-globin (Hbb) unit The structure of a human haemoglobin molecule All of the animals pictured above produce beta globin. It follows that they all must have a gene for beta globin. We can look at relationships between these animals by comparing their beta globin genes.
C G C A A T G A G C T A G G T C A T G G A Step 1: Scientists sequence the gene… Gene sequencing is used to determine the order of the base pairs in a segment of RNA or DNA . . . T T A C G A G G A G G G A A A G A A C T T T Each gene contains a triplet code for making a protein
Step 3: You compare gene sequences using computer programs You will use Biology WorkBench to run sequence alignments and then create a phylogenetic tree to explore relationships Ser Thr Glu Met Cys Leu Met Gly Gly Gene 1: TCA ACT GAG ATG TGT TTA ATG GGG GGA Gene 2: TCG ACA GGG ATA TAT CTA ATG GGT ATA * * * * * * * * * * * * * * * * * * Ser Thr Gly Ile Tyr Leu Met Gly Ile * Designates conservation of a nucleotide in both sequences.
Evolutionary distance since monotremes and marsupials diverged from a common ancestor Internal Nodes Terminal Nodes Step 4: You Construct Phylogenetic Trees A phylogenetic tree shows evolutionary relationships between various species. The use of the term "tree" has given rise to terms to describe the different parts of the overall tree: Branches terminate in a leaf (single species). Adding branch lengths can give an indication of evolutionary time since a divergence event. Nodes represent a branching point where two or more species diverged from a common ancestor.
UNROOTED PHYLOGENETIC TREE Leaf Node Leaf Branch Leaf Leaf Branch Leaf Branch Leaf Root Leaf Branch Leaf Rooted and Unrooted trees In a rooted tree, one sequence that is very distantly related to all the others is used to root the tree. When a distantly related sequence for comparison is not included, an unrooted tree is constructed. The unrooted tree is useful to examine clusters of related sequences (and therefore perhaps, species). ROOTED PHYLOGENETIC TREE
Get the sequence data • Click on the information bar to retrieve your sequence alignments for beta globin. • Save these sequences to the desktop for later use.
Run your sequence alignment • Click on the button below to launch Biology WorkBench. • Follow the instructions provided to run a sequence alignment and prepare a phylogenetic tree. You will use this to look at relationships between species based on a comparison of their beta globin genes. Biology WorkBench
Using Genomic Sequences Genomics is a rapidly expanding field in science. It is being used to answer many questions in a variety of fields: • Evolution and Genomes • How did eukaryotes evolve? • What is the origin of our species? • Genomic Identifications • How can we identify biological weapons? • How long can DNA survive? • How did tuberculosis reach North America? • How are newly emerging diseases identified? • Biomedical Genome Research • Can we use genomic sequences to make new vaccines? • Can we make new types of antibiotics? • Can we invent new types of medications? • How can E. coli be lethal and in our intestines at the same time?