Homology and Model Organisms
Homology is defined as the similarity of the structure and physiology of a biological component between organisms of different species [1]. It is important to understand how genes specifically compare in other species of distant relatedness to further understand the mechanisms by which genes and their phenotypes may have evolved. Homology can be used to to investigate these mechanisms by discovering conserved regions of a gene amongst different species. NCBI-BLAST techniques allow for the identification of homologs to the human VWF gene by running a diagnostic scan of the amino acid sequence of the gene of interest and the genes of other organisms [2]. Homology can then be used to identify organisms who may serve as excellent candidates for research on the gene of interest, typically referred to as Model Organisms. The homology and consequential model organisms for the study of VWF in this project are shown below.
Homology Results
Homo sapiens: (Human)
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Danio Rerio: (Zebrafish)
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Xenopus Tropicalis: (Western Clawed Frog)
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Phylogeny
"Phylogeny is the study of evolutionary relatedness amongst groups of organisms" [3]. Phylogenetics uses this idea and is the term for studying genetics through evolutionary trees. This research method determines relatedness based on genetic sequences and their alignments. Phylogenetic trees can be used to develop predictions about certain biological functions, as well as generate validating hypotheses in the face of genomic research. It is beneficial to examine the phylogenetics of a gene when researching its function within disease and the possible implications of genes on phenotypes [3].
Mega-X is the software that was used to perform phylogenetic analyses on VWF homolog amino acid sequences. The software aligns each sequence for each of the model organisms and can generate comparisons between the different organism sequences, a method known as bootstrapping [4]. There are two types of trees that are generated in this study: Neighbor-Joining and Maximum Likelihood trees. Maximum-likelihood trees are considered to be a more accurate and optimal method for mapping relatedness. The branches in this tree are organized at specific lengths to generate the maximum likelihood of that relation. Neighbor-joining trees use similarity scores of the sequence alignments and generate an output representing the species that are most likely closely related [5].
Mega-X is the software that was used to perform phylogenetic analyses on VWF homolog amino acid sequences. The software aligns each sequence for each of the model organisms and can generate comparisons between the different organism sequences, a method known as bootstrapping [4]. There are two types of trees that are generated in this study: Neighbor-Joining and Maximum Likelihood trees. Maximum-likelihood trees are considered to be a more accurate and optimal method for mapping relatedness. The branches in this tree are organized at specific lengths to generate the maximum likelihood of that relation. Neighbor-joining trees use similarity scores of the sequence alignments and generate an output representing the species that are most likely closely related [5].
Phylogenetic Results
Discussion
The Maximum-Likelihood tree shown above for VWF homologs shows that there are closely related organisms in terms of the VWF gene. The sequences for VWF across these organisms prove to be very well conserved, and the trees indicate that the use of any one of the homolog organisms would serve as great candidates for researching the functions of VWF. Of importance to note, Zebrafish (Danio Rerio) is seemingly the farthest relative on the tree, but is only one relation away from Humans (Homo Sapiens). This provides the foundational knowledge needed for looking to VWF in other organisms in correlation to human disease and genetic phenotypes.
References:
[1] Encyclopædia Britannica, inc. (2024, March 22). Homology. Encyclopædia Britannica. https://www.britannica.com/science/homology-evolution
[2] U.S. National Library of Medicine. (n.d.). Blast: Basic local alignment search tool. National Center for Biotechnology Information. https://blast.ncbi.nlm.nih.gov/
[3] Ziemert, N., & Jensen, P. R. (2012). Phylogenetic approaches to natural product structure prediction. Methods in enzymology, 517, 161–182. https://doi.org/10.1016/B978-0-12-404634-4.00008-5
[4] MegaX. Home. (n.d.). https://www.megasoftware.net/
[5] Tateno, Y., Takezaki, N., & Nei, M. (1994). Relative efficiencies of the maximum-likelihood, neighbor-joining, and maximum-parsimony methods when substitution rate varies with site. Molecular biology and evolution, 11(2), 261–277. https://doi.org/10.1093/oxfordjournals.molbev.a040108
[1] Encyclopædia Britannica, inc. (2024, March 22). Homology. Encyclopædia Britannica. https://www.britannica.com/science/homology-evolution
[2] U.S. National Library of Medicine. (n.d.). Blast: Basic local alignment search tool. National Center for Biotechnology Information. https://blast.ncbi.nlm.nih.gov/
[3] Ziemert, N., & Jensen, P. R. (2012). Phylogenetic approaches to natural product structure prediction. Methods in enzymology, 517, 161–182. https://doi.org/10.1016/B978-0-12-404634-4.00008-5
[4] MegaX. Home. (n.d.). https://www.megasoftware.net/
[5] Tateno, Y., Takezaki, N., & Nei, M. (1994). Relative efficiencies of the maximum-likelihood, neighbor-joining, and maximum-parsimony methods when substitution rate varies with site. Molecular biology and evolution, 11(2), 261–277. https://doi.org/10.1093/oxfordjournals.molbev.a040108
This web page was produced as an assignment for Genetics 564, a capstone course at UW-Madison.
Michelle Conte | [email protected] | Last edited 05/08/2024 | www.genetics564.weebly.com