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Old 10-12-2002, 06:57 PM   #1
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Post The urate oxidase pseudogene: the common ancestry of errors

The following evidence I feel amply demonstrates the common ancestry (and not "common design") of chimpanzees and human beings and why DNA homology is excellent evidence for evolution

the following is a multiple alignment of the sequences of human, chimp, orangutan and owl monkey urate oxidase sequences. The premature stop codon is in bold and italics.

Human Urate Oxidase Psuedogene CDS (exons 1-8)
<a href="http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=nucleotide&list_uids=20 513570&do" target="_blank">http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=nucleotide&list_uids=20 513570&do</a> pt=GenBank (see the end of the post for corroboration)

Orangutan Urate Oxidase pseudogene CDS (exons 1-8)
<a href="http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=nucleotide&list_uids=20 513597&dopt=GenBank" target="_blank">http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=nucleotide&list_uids=20 513597&dopt=GenBank</a>

Chimpanzee Urate Oxidase Pseudogene CDS (exons 1 -8)
<a href="http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=nucleotide&list_uids=20 513579&dopt=GenBank" target="_blank">http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=nucleotide&list_uids=20 513579&dopt=GenBank</a>

Spider Monkey Urate Oxidase (exons 1-8)
<a href="http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=nucleotide&list_uids=20 513645&dopt=GenBank" target="_blank">http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=nucleotide&list_uids=20 513645&dopt=GenBank</a>



[code]CLUSTAL X (1.81) multiple sequence alignment


human ATGGCCCACTACCATAACAACTATAAAAAGAATGATGAGGTGGAGTTTGT CCGAACTGGC
chimpanzee ATGGCCCACTACCATAACAACTATAAAAAGAATGATGAGGTGGAGTTTGT CCGAACTGGC
orangutan ATGGCCCACTACCGTAACAACTATAAAAAGAATGATGAGGTGGAGTTTGT CCGAACTGGC
owlmonkey ATGGCCCACTACCATAACGACTATAAAAAGAACGATGAGGTGGAGTTTGT ACGAACTGGC
************* **** ************* ***************** *********

human TATGGGAAGGAAATGGTAAAAGTTCTCCATATTCAGTGAGATGGAAAATATCACAGCATT
chimpanzee TATGGGAAGGATATGGTAAAAGTTCTCCATATTCAGTGAGATGGAAAATATCACAGCATT
orangutan TATGGGAAGGATATGGTAAAAGTTCTCCATATTCAGTGAGATGGAAAATATCACAGCATT
owlmonkey TATGGGAAGGATATGGTAAAAGTCCTCCATATTCAGCGAGATGGAAAATATCACAGCATT
*********** *********** ************ ***********************

human AAAGAGGTGGCAACTTCAGTGCAACTTACTCTAAGTTCCAAAAAAGATTA CCTGCATGGA
chimpanzee AAAGAGGTGGCAACTTCAGTGCAACTTACTCTAAGTTCCAAAAAAGATTA CCTGCATGGA
orangutan AAAGAGGTGGCAACTTCAGTGCAACTTACTCTGAGTTCCAAAAAAGATTA CCTGCATGGA
owlmonkey AAAGAGGTGGCAACTTCAGTGCAACTTACTCTGAGTTCCAAAAAAGATTA CCTGCATGGA
******************************** ***************************

human GATAATTCAGACATCATCCCTACAGACACCATCAAGAACACAGTTCATGT CTTGGCAAAG
chimpanzee GATAATTCAGACATCATCCCTACAGACACCATCAAGAACACAGTTCATGT CTTGGCAAAG
orangutan GATAATTCAGACATCATCCCTACAGACACCATCAAGAACACAGTTCATGT CTTGGCAAAG
owlmonkey GACAATTCAGATATCATCCCTACAGACACCATCAAGAACACAGTTCATGC CTTGGCAAAG
** ******** ************************************* **********

human TTTAAAGAAATCAAAAGCATAGAAGCCTTTGGTGTGAATATTTGTGAGCA TTTTCTTTCT
chimpanzee TTTAAAGAAATCAAAAGCATAGAAGCCTTTGGTGTGAATATTTGTGAGCA TTTTCTTTCT
orangutan TTTAAAGGAATCAAAAGCATAGAAGCCTTTGGTGTGAATATTTGTGAGCA TTTTCTTTCT
owlmonkey TTTAAAGGAATCAAAAGCATAGAAGCCTTTGCTGTGAATATTTGTCAGCA TTTTCTTTCT
******* *********************** ************* **************

human TCTTTTAACCATGTAATCCGAGCTCAAGTCTACATGGAAGAAATCCCTTG GAAGCATCTT
chimpanzee TCTTTTAACCATGTAATCCGAGCTCAAGTCTATGTGGAAGAAATCCCTTG GAAGCATCTT
orangutan TCTTTTAACCATGTAATCTGAGCTCAAGTCTACGTGGAAGAAATTCCTTG GAAGCATCTT
owlmonkey TCTTTTAACCATGTCATCCGAACTCAAGTCTATGTGGAAGAAATCCCTTG GAAGCGGCTT
************** *** ** ********** ********** ********** ***

human GGAAAGAATGGAGTTAAGCATGTCCATGCATTTATTCACACTCCCACTGG AACACACTTC
chimpanzee GAAAAGAATGGAGTTAAGCATGTCCATGCATTTATTCACACTCCCACTGG AACACACTTC
orangutan GAAAAGAATGGAGTTAAGCATGTCCATGCATTTATTCACACTCCCACTGG AACACACTTC
owlmonkey GAAAAGAATGGAGTTAAGCATGTCCATGCATTTATTCACACTCCCACTGG AACACACTTC
* ************************************************** ********

human TGTGAAGTTGAACAGCTGAGAAGTGGACCCCAAGTCATTCATTCTGGAAT CAAAGACCTC
chimpanzee GGTGAAGTTGAACAGCTGAGAAGTGGACCCCAAGTCATTCATTCTGGAAT CAAAGACCTC
orangutan TGTGAAGTTGAACAGCTGAGAAGTGGACCCCCAGTCATTCATTCTGGAAT CAAAGACCTC
owlmonkey TGTGA-GTTGAACAGCTGAGAAGTGGACCCCCAGTTATTCATTCTGGAATCAAAGA CCTC
**** ************************* *** ************************

human AAGGTCTTGAAAACAACACAGTCTGGATTTGAAGGTTTCATCAAGGACCA GTTCACTACC
chimpanzee AAGCTCTTGAAAACAACACAGTCTGGATTTGAAGGTTTCATCAAGGACCA GTTCACTACC
orangutan AAGGTCTTGAAAACAACATAGTCTCGATGTGACGGTTTCATCAAGGACCA GTTCACTACC
owlmonkey AAGGTCTTGAAAACAACCCAGTCTGGATTTGAAGGTTTCATCAAGGACCA GTTCACCACC
*** ************* ***** *** *** *********************** ***

human CTCCCTGAGGTGAAGGACTGATGCTTTGCCACCCAAGTGTACTGCAAGTG GCGCTACCAC
chimpanzee CTCCCTGAGGTGAAGGACTGATGCTTTGCCACCCAAGTGTACTGCAAGTG ACGCTACCAC
orangutan CTCCCTGAGGTGAAGGACCGATGCTTTGCCACCCAAGTGTACTGCAAGTG GCGCTACCAC
owlmonkey CTCCCTGAGGTGAAGGACCGATGCTTTGCCGCACAAGTATACTGCAAGTG GCGCTACCAC
****************** *********** * ***** *********** *********

human CAGTGCAGGGATGTGGACTTCAAGGCTACCTGGGACACCATTCGGGACCT TGTCATGGAG
chimpanzee CAGTGCAGGGATGTGGACTTCAAGGCTACCTGGGACACCATTCGGGACCT TGTCATGGAG
orangutan CAGTGCAGGGATGTGGACTTCGAGGCTACCTGGGACACCATTTGGGACCT TGTCCTGGAG
owlmonkey CAGTGCAGGGATGTGGACTTCGAGGCTACCTGGGACACCATTCGGGACGT TGTCCTAGAG
********************* ******************** ***** ***** * ***

human AAATCTGCTGGGCCCTATGACAAAGGTGAATACTTGACCTCTGTGCAGAA GACCCTCTGT
chimpanzee AAATCTGCTGGGCCCTATGACAAAGATGAATACTCGCCCTCTGTGCAGAA GACCCTCTGT
orangutan AAATCTGCTGGGCCNTATGACAAAGGCGAATACTTGCCCTCTGTGCAGAA GACCCTCTAT
owlmonkey AAATTTGCTGGGCCCTATGACAAAGGCGAGTACTCGCCGTCTGTGCAGAA GACCCTCTAT
**** ********* ********** ** **** * * ******************* *

human GATATCCAGGTGCTCTCCCTGAGCCGAGTTCCTGCGATAGAAGATATGGA AATCAGCCTG
chimpanzee GATATCCAGGTGCTCTCCCTGAGCCGAGTTCCTGCGATAGAAGATATGGA AATCAGCCTG
orangutan GATATCCAGGTGCTCTCCCTGTGCCGAGTTCCTGAGATAGAAGATATGGA AATCAGCCTG
owlmonkey GATATCCAGGTGGTCTCCCTGAGTCAAGTCCCTGAGATAGACGATATGGA AATCAGCCTG
************ ******** * * *** **** ****** ******************

human CCAAACATTCACTACTTCAACATAGACATGTCCAAAATGGGTCTGATCAA CAAGGAAGAG
chimpanzee CCAAACATTCACTACTTCAACATAGACATGTCCAAAATGGGTCTGATCAA CAAGGAAGAG
orangutan CCAAACATTCACTACTTCAACATAGACATGTCCAAAATGGGTCTGATCAA CAAGGAAGAG
owlmonkey CCAAACATTCACTACTTCAACATAGACATGTCCAAAATGGGTCTGATCAA CAAGGAAGAG
************************************************** **********

human GTCTTGCTGCCATTAGACAATCCATATGGAAAAATTACTGGTACAGTCAA GAGGAAGTTG
chimpanzee GTCTTGCTGCCATTAGACAATCCATATGGAAAAATTACTGGTACAGTCAA GAGGAAGTTG
orangutan GTCTTGCTGCCATTAGACAATCCATATGGAGAAATTACTGGTACAGTCAA GAGGAAGTTG
owlmonkey GTCTTGCTGCCATTAGACAATCCATATGGCAAAATTACTGGTACAGTCAA GAGGAAGTTG
***************************** *****************************

human TCTTCAAGACTGTGA
chimpanzee TCTTCAAGACTGTGA
orangutan TCTTCAAGACTGTGA
owlmonkey TCTTCGAGACTGTGA
***** *********</pre>[/quote]
*'s represent nucleotides that are identical. Spaces indicate differences.

Human Urate Oxidase Pseudogene translated:

Met A H Y H N N Y K K N D E V E F V R T G Y G K E Met V K V L H I Q Stop D G K Y H S I K E V A T S V Q L T L S S K K D Y L H G D N S D I I P T D T I K N T V H V L A K F K E I K S I E A F G V N I C E H F L S S F N H V I R A Q V Y Met E E I P W K H L G K N G V K H V H A F I H T P T G T H F C E V E Q L R S G P Q V I H S G I K D L K V L K T T Q S G F E G F I K D Q F T T L P E V K D Stop C F A T Q V Y C K W R Y H Q C R D V D F K A T W D T I R D L V Met E K S A G P Y D K G E Y L T S V Q K T L C D I Q V L S L S R V P A I E D Met E I S L P N I H Y F N I D Met S K Met G L I N K E E V L L P L D N P Y G K I T G T V K R K L S S R L Stop


Notice the translated sequence of the pseudogene has several "premature stop codons"
A premature stop codon is one that appears in the middle of a gene, rather than at the end. What this effectively does is truncate the protein - it is no longer translated to the end.

i.e. instead of getting the entire sequence translated, what you get instead is

Met A H Y H N N Y K K N D E V E F V R T G Y G K E Met V K V L H I Q Stop

This renders the gene non-functional. It is severely truncated, it is missing its C- terminal signal peptide which targets it to peroxisome, where it would usually function. Its also missing about 90 percent of the original protein. The premature stop codon occurs in the same place in humans, gorillas, chimpanzees and orangutans

A fully functional copy of urate oxidase

<a href="http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=nucleotide&list_uids=20 513645&dopt=GenBank" target="_blank">http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=nucleotide&list_uids=20 513645&do pt=GenBank</a>

Aotus trivirgatus (owl monkey) urate oxidase gene:

atggcccact accataacga ctataaaaag aacgatgagg tggagtttgt acgaactggc tatgggaagg atatggtaaa agtcctccat attcagcgag atggaaaata tcacagcatt aaagaggtgg caacttcagt gcaacttact ctgagttcca aaaaagatta cctgcatgga gacaattcag atatcatccc tacagacacc atcaagaaca cagttcatgc cttggcaaag tttaaagga atcaaaagca tagaagcctt tgctgtgaat atttgtcagc attttctttc ttcttttaac catgtcatcc gaactcaagt ctatgtggaa gaaatccctt ggaagcggct tgaaaag aatggagtta agcatgtcca tgcatttatt cacactccca ctggaacaca cttctgtga gttgaacagc tgagaagt ggacccccag ttattcattc tggaatcaaa gacctcaagg tcttgaaaac aacccagtct ggatttgaag gtttcatcaa ggaccagttc accaccctcc ctgaggtgaa ggaccgatgc tttgccgcac aagtatactg caagtggcgc taccaccagt gcagggatgt ggacttcgag gctacctgg gacaccattc gggacgttgt cctagagaaa tttgctgggc cctatgacaa aggcgagtac tcgccgtctg tgcagaagac cctctatgat atccaggtgg tctccctgag tcaagtccct gagatagacgata tggaaatcag cctgccaaac attcactact tcaacataga catgtccaaa atgggtctga tcaacaagga agaggtcttgctgc cattagacaa tccatatggc aaaattactg gtacagtcaa gaggaagttg tcttcgagac tgtga

Translation:

Met A H Y H N D Y K K N D E V E F V R T G Y G K D Met V K V L H I Q R D G K Y H S I K E V A T S V Q L T L S S K K D Y L H G D N S D I I P T D T I K N T V H A L A K F K G I K S I E A F A V N I C Q H F L S S F N H V I R T Q V Y V E E I P W K R L E K N G V K H V H A F I H T P T G T H F C E V E Q L R S G P P V I H S G I K D L K V L K T T Q S G F E G F I K D Q F T T L P E V K D R C F A A Q V Y C K W R Y H Q C R D V D F E A T W D T I R D V V L E K F A G P Y D K G E Y S P S V Q K T L Y D I Q V V S L S Q V P E I D D Met E I S L P N I H Y F N I D Met S K Met G L I N K E E V L L P L D N P Y G K I T G T V K R K L S S R L Stop

Blast pairwise alignments:

human/owl monkey:

Score = 1483 bits (771), Expect = 0.0
Identities = 867/915 (94%)
Strand = Plus / Plus

As you can no doubt see, this functional copy has only one stop codon, at the end of the protein. It is also 94 percent homologous to the pseudogenes in humans.

some additional information:

Function of urate oxidase:

<a href="http://www.biochem.missouri.edu/ptipton_urate.html" target="_blank">http://www.biochem.missouri.edu/ptipton_urate.html</a>

Nonsense mediated Decay:

<a href="http://www.ncbi.nlm.nih.gov/Coffeebreak/CB7_NMD/page.html" target="_blank">http://www.ncbi.nlm.nih.gov/Coffeebreak/CB7_NMD/page.html</a>

Quote:
Hypertension 2002 Sep;40(3):355-60
Related Articles, Links


Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity.

Watanabe S, Kang DH, Feng L, Nakagawa T, Kanellis J, Lan H, Mazzali M, Johnson RJ.

Division of Nephrology, Baylor College of Medicine, Houston, Tex 77030, USA.

Humans have elevated serum uric acid as a result of a mutation in the urate oxidase (uricase) gene that occurred during the Miocene. We hypothesize that the mutation provided a survival advantage because of the ability of hyperuricemia to maintain blood pressure under low-salt dietary conditions, such as prevailed during that period. Mild hyperuricemia in rats acutely increases blood pressure by a renin-dependent mechanism that is most manifest under low-salt dietary conditions. Chronic hyperuricemia also causes salt sensitivity, in part by inducing preglomerular vascular disease. The vascular disease is mediated in part by uric acid-induced smooth muscle cell proliferation with activation of mitogen-activated protein kinases and stimulation of cyclooxygenase-2 and platelet-derived growth factor. Although it provided a survival advantage to early hominoids, hyperuricemia may have a major role in the current cardiovascular disease epidemic.

PMID: 12215479 [PubMed - indexed for MEDLINE]
Quote:
: Semin Hematol 2001 Oct;38(4 Suppl 10):13-21
Related Articles, Links


Urate oxidase in the prophylaxis or treatment of hyperuricemia: the United States experience.

Pui CH.

St. Jude Children's Research Hospital, and Department of Pediatrics, University of Tennessee, College of Medicine, Memphis, TN 38105, USA.

Nonrecombinant urate oxidase (Uricozyme, Sanofi-Synthelabo, Inc, Paris, France) is a highly effective uricolytic agent, but its use is associated with hypersensitivity reaction manifested mainly by bronchospasm in approximately 5% of patients. Recently, several multi-institutional studies have evaluated the efficacy and safety of a recombinant urate oxidase (rasburicase). In a phase I/II study, all 131 patients with newly diagnosed acute lymphoblastic leukemia (ALL) or stage III/IV non-Hodgkin's lymphoma (NHL) experienced rapidly decreased plasma uric acid concentrations after receiving recombinant urate oxidase. Serum creatinine levels also decreased significantly. Toxicity was negligible, and none of the patients required dialysis. In a phase III trial, children with newly diagnosed ALL or stage III/IV NHL were stratified and randomized to receive recombinant urate oxidase or allopurinol. Results showed that the 27 patients who received recombinant urate oxidase had a significantly lower plasma uric acid concentration and a more rapid decline in serum creatinine level than did the 25 who took allopurinol. One patient in the recombinant urate oxidase group had hemolysis of unknown cause, and one in the allopurinol group required hemofiltration for hyperphosphatemia. To further assess the safety profile of recombinant urate oxidase, the data on 245 patients (173 children and 72 adults) who received this agent in a compassionate-use program were reviewed retrospectively. The drug produced dramatic decreases in uric acid concentrations in all patients. Nine patients (four children and five adults) had mild adverse reactions that were drug-related or of unknown etiology. These data suggest that recombinant urate oxidase is safe and effective in the prophylaxis and treatment of hyperuricemia associated with malignancy or chemotherapy. Copyright 2001 by W.B. Saunders Company.

PMID: 11694947 [PubMed - indexed for MEDLINE]
So, what we have is homologous DNA in humans and chimps which has no function. The "Common design" hypothesis states that DNA homology is due not to evolutionary relationships but due to similar function. This DNA has no function, so why is it homologous?

If you want anything explained, just ask

Quote:
Oda M, Satta Y, Takenaka O, Takahata N. Loss of urate oxidase activity in hominoids and its evolutionary implications. Mol Biol Evol 2002 May;19(5):640-53
Quote:
Yeldandi AV, Patel YD, Liao M, Kao FT, Rao MS, Reddy JK, Le Beau MM. Localization of the human urate oxidase gene (UOX) to 1p22.Cytogenet Cell Genet 1992;61(2):121-2

Quote:
Wu XW, Lee CC, Muzny DM, Caskey CT. Urate oxidase: primary structure and evolutionary implications. Proc Natl Acad Sci U S A 1989 Dec;86(23):9412-6
[ October 13, 2002: Message edited by: monkenstick ]</p>
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Old 10-12-2002, 07:17 PM   #2
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Hey, thanks, Monkenstick, for this expanded version of this stuff! I posted the human and chimp sequences on three different creationist-dominated fora maybe a month ago (after Van gave you no answers here) and have gotten NO answers yet. They don't seem to like hard questions.

(Well, I got one answer when I asked "Was it common ancestry or Bonzo getting cursed along with Adam and Eve?" He chose the latter.)
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Old 10-12-2002, 08:43 PM   #3
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monkenstick,

I have an idea of how to present this argument better though it will require it be done as a web page.

You give three rather lengthy nucleotide sequences. (Okay lengthy to a human reader not lengthy in genomic terms.) Unless a person slowly compares the "letters" one-by-one this (and how many readers will do this?), the identities will not be obvious. What needs to be done is to use a monospaced font and to put the three on top of each other.

[code]
atggcccact accataacaa ctataaaaaga atgatgagg tggagtttgt ccgaactggc tatgggaagg aaatggtaaa agttctccat attcagtgag
atggcccact accataacaa ctataaaaag aatgatgagg tggagtttgt ccgaactggc tatgggaagg atatggtaaa agttctccat attcagtgag
atggcccact accataacga ctataaaaag aacgatgagg tggagtttgt acgaactggc tatgggaagg atatggtaaa agtcctccat attcagcgag
</pre>[/quote]

Different colors could code for similarity or differences.

Then you can explain what blast is. Many of us here know what it is, but 99% of average Joes don't know and can't be faulted for not knowing.
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Old 10-12-2002, 08:50 PM   #4
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yeah, I tried posting a clustalw alignment and a blast alignment but the formatting gets ruined so you can't really see the alignment - I might right it up properly as a html document and post it somewhere.
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Old 10-12-2002, 10:40 PM   #5
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Angry

that was such a pain in the arse...

I don't know the code to make it all line up properly so I had to use dots, and x's

anyway, i think its clear enough now
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Old 10-12-2002, 10:47 PM   #6
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One thing: those "[ October 12, 2002: Message edited by: monkenstick ]" lines aren't hard-coded; if you edit it one more time, you can get rid of them all and when you save it one last time, only one will be present at the bottom.

Other than that, excellent post (and it got even better from the last time around.)

Edit: The [ CODE ] [ / CODE ] (without the spaces) UBB command is the one that will display in a monospaced font, which will make it line up as was indicated.

[code]Like this</pre>[/quote]

[ October 12, 2002: Message edited by: Kevin Dorner ]</p>
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Old 10-12-2002, 10:52 PM   #7
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MS,

Use code brackets; they should allow you to use extra spaces to align sequences. Example.

[code]
human ATGGCCCACTACCATAACAACTATAAAAAGAATGATGAGGTGGAGTTTGT CCGAACTGGC
chimpanzee ATGGCCCACTACCATAACAACTATAAAAAGAATGATGAGGTGGAGTTTGT CCGAACTGGC
orangutan ATGGCCCACTACCGTAACAACTATAAAAAGAATGATGAGGTGGAGTTTGT CCGAACTGGC
************* **********************************************
</pre>[/quote]

See how it works. Just put your info with in [ code ] and [ /code ], minus the spaces.

Edited to Add:
Looks like Kevin and I had the same idea.

[ October 12, 2002: Message edited by: RufusAtticus ]</p>
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Old 10-12-2002, 10:57 PM   #8
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Also, do you have any data on phylogenic trees constructed with this pseudogene?
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Old 10-12-2002, 11:25 PM   #9
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no rufus, I can't get the original article through my university's proxy so I don't know, I could make some with phylip, but i'd have to upload them to a website - I might try making a webpage out of this
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Old 10-13-2002, 12:42 PM   #10
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Quote:
I might try making a webpage out of this
Please! And maybe see if the GLO pseudogene has similar sequence data available. I get so tangled up in acronyms that I can't make good sense out of GenBank, myself..
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