This web page was produced as an assignment for an undergraduate course at Davidson College
Leptin Orthologs
In this assignment I will examine different orthologs for the leptin protein. For more information about the structure and function of leptin, please visit my previous web page by clicking here.
Introduction:
I performed a protein-protein BLAST using the amino acid sequence of the human leptin protein which can be found below.
Figure 1: Amino acid sequence of the human leptin protein. This is the form of leptin that was used to create the crystal structure of the protein. Sequence obtained from NCBI.
The protein-protein BLAST returned approximately 80 hits. I examined only the hits that had a score of 200 or more in order to obtain the most similar sequences and therefore the highest probability of finding an ortholog. These hits can been seen below.
Figure 2. Protein-protein BLAST results. Only the hits that had a score of 200 or more are shown here. To see the full results of the search, click here and copy and paste the following Request ID - 1110337281-5370-68561471732.BLASTQ2.
Orthologs:
It can be seen from the figure above that most of the species represented are mammalian. In order to get a better understanding of all possible orthologs, I performed specific searches for the following species: Mouse, C. elegans, Drosophila, Arabidopsis, Yeast, and E. coli. Figures 3 and 4 display the results of these searches. The Query line is the sequence of the form of leptin that was used to create the crystal structure.
Figure 3. Protein-protein BLAST results of the human leptin protein vs. the mouse leptin protein. Query is the human sequence and Sbjct is the mouse sequence. It can been seen from these results that there is a high degree of similarity between the human and mouse leptin sequences.
Figure 4. Protein-protein BLAST results of the human leptin protein vs. S. cerevisiae. Query is the human sequence and Sbjct is the S. cerevisiae sequence. It can been seen from these results that there is not a very high sequence similarity between these two species.
A search of Arabidopsis, Drosophila, C. elegans and E. coli did not return any results. It can be assumed that there are no similar sequences in the genomes of these two species. Due to the high sequence similarity of mammalian species and low sequence similarity among non-mammalian species, I performed several more searches using other higher mammalian species to see if they would also have a high sequence similarity. I obtained the following results.
Figure 5. Protein-protein BLAST results of the human leptin protein vs. the chimpanzee leptin protein. Query is the human sequence and Sbjct is the chimpanzee sequence. It can be seen from this figure that the leptin protein is 99% conserved among both species.
Figure 6. Protein-protein BLAST results of the human leptin protein vs. the gorilla leptin protein. Query is the human sequence and Sbjct is the gorilla sequence. It can be seen from this figure that the leptin protein is 99% conserved among both species.
Figure 7. Protein-protein BLAST results of the human leptin protein vs. the orangutan leptin protein. Query is the human sequence and Sbjct is the orangutan sequence. It can be seen from this figure that the leptin protein is 97% conserved among both species.
Figure 8. Protein-protein BLAST results of the human leptin protein vs. the cat leptin protein. Query is the human sequence and Sbjct is the cat sequence. It can be seen from this figure that the leptin protein is highly conserved among both species.
Evolution:
Among the other hits that had a score of 200 or more (meaning there was a high degree of sequence similarity) were such diverse species as rat, water buffalo, dog, chicken, sheep, horse, pig, turkey, harbor seal, red fox and gray seal. The BLAST results listed the Sbjct sequence as that of leptin or a leptin precursor. It is important to note however that all of these species are mammalian and that no prokaryotic species had a high degree of sequence similarity. These results lend further support to the fact that leptin is involved in obesity. A prokaryotic organism would not need a protein that acts as a lipostat while a mammal would need such a protein.
A study performed by Moffett, et al. in 2002 sequenced the leptin gene of approximately 2,000 individuals from 12 different world populations. The abstract of their paper states, "Common alleles shared among populations, alleles specific to geographically defined populations, and the homologous alleles in the common and pygmy chimpanzee, the gorilla and the orangutan, were sequenced to define the allelic variation at the nucleotide level. These data reveal a common set of alleles shared among world populations, presumed to have arisen from a great ape ancestral allele prior to the divergence of the major geographical subdivisions of the human population, a subset of alleles specific to populations of African ancestry and a second set of alleles that arose by tandem duplication of the core repeat unit following the separation of African and non-African populations" (Moffett, et al., 2002). The findings of this group support the search results I found that indicate a strong sequence similarity among ape species.
References:
Moffett, et al. Genetic diversity and evolution of the human leptin locus tetranucleotide repeat. Hum. Genet. 110, 412-417 (2002).
NCBI. 2005. <http://www.ncbi.nlm.nih.gov/> Accessed 8 March 2005.
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