“Jurassic Park” Dino-DNA Analysis
In 1990, Michael Crichton published the book “Jurassic Park” about the resurrection of dinosaurs using the blood from the stomachs of insects which had been encased in tree sap, later turned into amber.
At one point in the book, Dr. Henry Wu is asked to explain some of DNA techniques used in reconstructing the extinct dinosaur genomes. Dr. Wu describes the use of restriction enzymes and how the fragmented pieces of dino DNA can be spliced together with these enzymes. He also alludes to the fact that they don’t have the entire genome but that they “fill in the gaps” with modern day frog DNA.
At one point during his discussion he points to a computer screen and remarks “Here you see the actual structure of a small fragment of dinosaur DNA.”
In 1992, Dr. Mark Boguski, at the National Center for Biotechnology Information, NCBI, having read the book “Jurassic Park” entered this sequence into a text editor and searched all of the known DNA sequences at the time. This collection of sequences make up a database referred to as GENBANK. Mark wrote up his findings and submitted a manuscript to the journal BioTechniques, as a tongue-in-cheek joke. His manuscript was accepted and published.
(Boguski, M.S. A Molecular Biologist Visits Jurassic Park. (1992) BioTechniques 12(5):668-
669).
Any person reading “Jurassic Park” who had access to a web browser could have performed this pure bioinformatics experiment and submitted an article for publication. You will reproduce Mark’s experiment by using select, copy and paste to send this sequence for comparison against the GENBANK database just as Mark did in 1992.
To learn more about an “unknown” sequence, one of the first steps is to use a bioinformatics program such as BLAST (Basic LocalAlignment Search Tools) to search databases for similar known sequences.
BLAST compares a query sequence to all sequences in a specified database in a pair-wise fashion. Each comparison is given a score, reflecting the degree of similarity between the query sequence and the sequence being compared. Discriminating between real and random matches is done using an estimate of probability that the match might occur by chance. The significance of each alignment is computed as an E value, a statistical measure of significance. In general, the smaller the E value, the better the match between sequences.
>JurassicPark DinoDNA from the book Jurassic Park gcgttgctgg cgtttttcca taggctccgc ccccctgacg agcatcacaa aaatcgacgc ggtggcgaaa cccgacagga ctataaagat accaggcgtt tccccctgga agctccctcg tgttccgacc ctgccgctta ccggatacct gtccgccttt ctcccttcgg gaagcgtggc tgctcacgct gtaggtatct cagttcggtg taggtcgttc gctccaagct gggctgtgtg ccgttcagcc cgaccgctgc gccttatccg gtaactatcg tcttgagtcc aacccggtaa agtaggacag gtgccggcag cgctctgggt cattttcggc gaggaccgct ttcgctggag atcggcctgt cgcttgcggt attcggaatc ttgcacgccc tcgctcaagc cttcgtcact ccaaacgttt cggcgagaag caggccatta tcgccggcat ggcggccgac gcgctgggct ggcgttcgcg acgcgaggct ggatggcctt ccccattatg attcttctcg cttccggcgg cccgcgttgc aggccatgct gtccaggcag gtagatgacg accatcaggg acagcttcaa cggctcttac cagcctaact tcgatcactg gaccgctgat cgtcacggcg atttatgccg caagtcagag gtggcgaaac ccgacaagga ctataaagat accaggcgtt tcccctggaa gcgctctcct gttccgaccc tgccgcttac
cggatacctg tccgcctttc tcccttcggg ctttctcatt gctcacgctg taggtatctc agttcggtgt aggtcgttcg ctccaagctg acgaaccccc cgttcagccc gaccgctgcg ccttatccgg taactatcgt cttgagtcca acacgactta acgggttggc atggattgta ggcgccgccc tataccttgt ctgcctcccc gcggtgcatg gagccgggcc acctcgacct gaatggaagc cggcggcacc tcgctaacgg ccaagaattg gagccaatca attcttgcgg agaactgtga atgcgcaaac caacccttgg ccatcgcgtc cgccatctcc agcagccgca cgcggcgcat ctcgggcagc gttgggtcct gcgcatgatc gtgctagcct gtcgttgagg acccggctag gctggcgggg ttgccttact atgaatcacc gatacgcgag cgaacgtgaa gcgactgctg ctgcaaaacg tctgcgacct atgaatggtc ttcggtttcc gtgtttcgta aagtctggaa acgcggaagt cagcgccctg
Exercise 1
1. Go to the NCBI website (http://www.ncbi.nlm.nih.gov/). Click on “BLAST” and then “Nucleotide BLAST” (under Basic BLAST). Select, copy, and paste the sequence shown above into area labeled “Enter accession number, gi, or FASTA sequence”. Select the “Others (nr etc.)” option for databases but otherwise keep the default settings. At the bottom of the page, click the box for “Show results in a new window.” Then click the BLAST button at the bottom of the page.
2. Familiarize yourself with the results by following the various links to the alignments and GENBANK database entries. Follow the links are far as you can or as far as seems reasonable.
3. What are a few of the organisms that had sequences that best matched the dinosaur DNA sequence from “Jurassic Park?” Note that sequences with equal “E values” are equally similar to your query sequence.
4. Delete the Jurassic Park sequence from the Query field and replace it with about 100 random nucleotides. What kind of BLAST results do you get with random sequence?
5. From your results do you really believe what Dr. Wu is claiming? Did Michael Crichton just type random A, C, G, T letters or do you think he knew about GENBANK and borrowed some DNA?
“The Lost World” Dino-DNA Analysis
Mark’s published article was brought to Michael Crichton’s attention. In his second book, “The Lost World”, Mr. Crichton used Mark as a consultant. Mark chose a DNA sequence from a living organism which is much more closely related to the dinosaurs.
Mark also mixed in some frog, Xenopus, DNA just like Dr. Wu described to fill in the holes in their dino-genomes. However, Mark played a little trick on Mr. Crichton by embedding a message in the protein translation of the DNA sequence which he submitted for use in the book.
Here is the sequence Mark gave Michael Crichton for the book “The Lost
World”:
>LostWorld DinoDNA from the book The Lost World gaattccgga agcgagcaag agataagtcc tggcatcaga tacagttgga gataaggacg gacgtgtggc agctcccgca gaggattcac tggaagtgca ttacctatcc catgggagcc atggagttcg tggcgctggg ggggccggat gcgggctccc ccactccgtt ccctgatgaa gccggagcct tcctggggct gggggggggc gagaggacgg aggcgggggg gctgctggcc tcctaccccc cctcaggccg cgtgtccctg gtgccgtggg cagacacggg tactttgggg accccccagt gggtgccgcc cgccacccaa atggagcccc cccactacct ggagctgctg caaccccccc ggggcagccc cccccatccc tcctccgggc ccctactgcc actcagcagc gggcccccac cctgcgaggc ccgtgagtgc gtcatggcca ggaagaactg cggagcgacg gcaacgccgc tgtggcgccg ggacggcacc gggcattacc tgtgcaactg ggcctcagcc tgcgggctct accaccgcct caacggccag aaccgcccgc tcatccgccc caaaaagcgc ctgcgggtga gtaagcgcgc aggcacagtg tgcagccacg agcgtgaaaa ctgccagaca tccaccacca ctctgtggcg tcgcagcccc atgggggacc ccgtctgcaa caacattcac gcctgcggcc tctactacaa actgcaccaa gtgaaccgcc ccctcacgat gcgcaaagac ggaatccaaa cccgaaaccg
caaagtttcc tccaagggta aaaagcggcg ccccccgggg gggggaaacc cctccgccac cgcgggaggg ggcgctccta tggggggagg gggggacccc tctatgcccc ccccgccgcc ccccccggcc gccgcccccc ctcaaagcga cgctctgtac gctctcggcc ccgtggtcct ttcgggccat tttctgccct ttggaaactc cggagggttt tttggggggg gggcgggggg ttacacggcc cccccggggc tgagcccgca gatttaaata ataactctga cgtgggcaag tgggccttgc tgagaagaca gtgtaacata ataatttgca cctcggcaat tgcagagggt cgatctccac tttggacaca acagggctac tcggtaggac cagataagca ctttgctccc tggactgaaa aagaaaggat ttatctgttt gcttcttgct gacaaatccc tgtgaaaggt aaaagtcgga cacagcaatc gattatttct cgcctgtgtg aaattactgt gaatattgta aatatatata tatatatata tatatctgta tagaacagcc tcggaggcgg catggaccca gcgtagatca tgctggattt gtactgccgg aattc
Exercise 2
1. Select, copy, and paste the “Lost World” sequence shown above into the Nucleotide
BLAST Search web form. Make sure the “others (nr etc.)” database is selected.
2. In the table of matches, follow the link to the GENBANK entry of the best match, this link is in the left most column labeled “Accession.” On that page find the ORGANISM keyword and click on the species link. This will bring up the species category of this organism. Do any of the terms imply a relationship to the dinosaurs? Click there to look
at other descendents to the dinosaurs. What organism did Mark choose as being his living dinosaur? What is its common name? What is species for the second best match? What
is its common name?
3. Go back to the main BLAST page. Click on “BLASTx.” This type of search translates the DNA sequence to six protein sequences (all three reading frames and forward or reverse) and searches the protein database. This search takes longer but is much informative about the relationship between the probe DNA sequence and the hits in the database. Select, copy, and paste the “Lost World” sequence into the Query Sequence form. Proteins use 20 letters instead of 4, this made it easier for Mark to create a hidden message. When the analysis is finished look at the best pairwise alignment by clicking on the score value in the right hand column or scroll down past the hit list to the first alignment – What was Mark’s hidden message?
Answer each of the six questions and copy and paste your answers into the Canvas submission box.
“Jurassic Park” Dino-DNA Analysis
1. What are a few of the organisms that had sequences that best matched the dinosaur DNA sequence from “Jurassic Park?” Note that sequences with equal “E values” are equally similar to your query sequence.
2. What kind of BLAST results do you get with random sequence?
3. From your results do you really believe what Dr. Wu is claiming? Did Michael Crichton just type random A, C, G, T letters or do you think he knew about GENBANK and borrowed some DNA?
“The Lost World” Dino-DNA Analysis
4. What organism did Dr. Mark Boguski choose as being his living dinosaur? What is its common name? Why did he choose this species?
5. What is species for the second best match? What is its common name? Why was this species selected?
6. What was Mark’s hidden message in the amino acid sequence?
