Consequently, the insulin molecule is critical to healthy functioning of vertebrate animals. The gene that codes for insulin is well known, and has been mapped in a multiplicity of organisms, including organisms whose
entire genomes have been sequenced, ranging from the pufferfish
Tetraodon nigroviridis through to
Homo sapiens. There is
demonstrable variability in insulin molecules (and the genes coding for them) across the entire panoply of vertebrate taxa. Bovine insulin, for example, is not
identical to human insulin. I refer everyone to the following gene sequences, all of which have been obtained from publicly searchable online gene databases:
[1]
Human insulin gene on Chromosome 11, which is as follows:
atg gcc ctg tgg atg cgc ctc ctg ccc ctg ctg gcg ctg ctg gcc ctc tgg gga cct gac
cca gcc gca gcc ttt gtg aac caa cac ctg tgc ggc tca cac ctg gtg gaa gct ctc tac
cta gtg tgc ggg gaa cga ggc ttc ttc tac aca ccc aag acc cgc cgg gag gca gag gac
ctg cag gtg ggg cag gtg gag ctg ggc ggg ggc cct ggt gca ggc agc ctg cag ccc ttg
gcc ctg gag ggg tcc ctg cag aag cgt ggc att gtg gaa caa tgc tgt acc agc atc tgc
tcc ctc tac cag ctg gag aac tac tgc aac tag
which codes for the following protein sequence (using the standard single letter mnemonics for individual amino acids, which I have colour coded to match the colour coding in
this diagram of the insulin synthesis pathway in humans):
MALWMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKT
RREAEDLQVGQVELGGGPGAGSLQPLALEGSLQKR
GIVEQCCTSICSLYQLENYCN
Now, I refer everyone to
this data, which is the coding sequence for insulin in the Lowland Gorilla (differences are highlighted in boldface):
atg gcc ctg tgg atg cgc ctc ctg ccc ctg ctg gcg ctg ctg gcc ctc tgg gga cct gac
cca gcc
gcg gcc ttt gtg aac caa cac ctg tgc ggc
tcc cac ctg gtg gaa gct ctc tac
cta gtg tgc ggg gaa cga ggc ttc ttc tac aca ccc aag acc cgc cgg gag gca gag gac
ctg cag gtg ggg cag gtg gag ctg ggc ggg ggc cct ggt gca ggc agc ctg cag ccc ttg
gcc ctg gag ggg tcc ctg cag aag cgt ggc
atc gtg gaa
cag tgc tgt acc agc atc tgc
tcc ctc tac cag ctg gag aac tac tgc aac tag
this codes for the protein sequence:
MALWMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKT
RREAEDLQVGQVELGGGPGAGSLQPLALEGSLQKR
GIVEQCCTSICSLYQLENYCN
which so happens to be the
same precursor protein. However, Gorillas are closely related to humans. Let's move a little further away, to the domestic cow,
Bos taurus (whose sequence is found
here):
atg gcc ctg tgg aca cgc ctg cgg ccc ctg ctg gcc ctg ctg gcg ctc tgg ccc ccc ccc
ccg gcc cgc gcc ttc gtc aac cag cat ctg tgt ggc tcc cac ctg gtg gag gcg ctg tac
ctg gtg tgc gga gag cgc ggc ttc ttc tac acg ccc aag gcc cgc cgg gag gtg gag ggc
ccg cag gtg ggg gcg ctg gag ctg gcc gga ggc ccg ggc gcg ggc ggc ctg gag ggg ccc
ccg cag aag cgt ggc atc gtg gag cag tgc tgt gcc agc gtc tgc tcg ctc tac cag ctg
gag aac tac tgt aac tag
Already this is a smaller sequence - 318 codons instead of 333 - so we KNOW we're going to get a different insulin molecule with this species ... which is as follows:
MALWTRLRPLLALLALWPPPPARAFVNQHLCGSHLVEALYLVCGERGFFYTPK
ARREVEGPQVGALELAGGPGAGGLEGPPQKRGIVE
QCCASVCSLYQLENYCN
clearly a
different protein, but one which
still functions as an insulin precursor and results in a mature insulin molecule in cows, one which
differs in exact sequence from that in humans. Indeed, prior to the advent of transgenic bacteria, into which human insulin genes had been transplanted for the purpose of harnessing those bacteria to produce human insulin for medical use, bovine insulin harvested from the pancreases of slaughtered beef cows was used to treat diabetes mellitus in humans. Now, of course, with the advent of transgenically manufactured true human insulin, from a sterile source, bovine insulin is no longer needed, much to the relief of those who are aware of the risk from BSE.
Moving on again, we have a
different coding sequence from the tropical Zebrafish,
Danio rerio, (sequence to be found
here) which is as follows:
atg gca gtg tgg ctt cag gct ggt gct ctg ttg gtc ctg ttg gtc gtg tcc agt gta agc
act aac cca ggc aca ccg cag cac ctg tgt gga tct cat ctg gtc gat gcc ctt tat ctg
gtc tgt ggc cca aca ggc ttc ttc tac aac ccc aag aga gac gtt gag ccc ctt ctg ggt
ttc ctt cct cct aaa tct gcc cag gaa act gag gtg gct gac ttt gca ttt aaa gat cat
gcc gag ctg ata agg aag aga ggc att gta gag cag tgc tgc cac aaa ccc tgc agc atc
ttt gag ctg cag aac tac tgt aac tga
And this sequence codes for the following protein:
MAVWLQAGALLVLLVVSSVSTNPGTPQHLCGSHLVDALYLVCGPTFTGFFYNP
KRDVEPLLGFLPPKSAQETEVADFAFKDHAELIRK
RGIVEQCCHKPCSIFELQNYCN
so again we have a
different insulin precursor protein that is ultimately converted into a
different insulin molecule within the Zebra Fish
