What is gene homology?
Genes derived from common ancestors have similar characteristics in both sequence and function. These conserved genes, mRNA and proteins can be classified as homologous. Homologous sequences have a slight variation amongst species that can shed light on its molecular mechanisms and clinical applications. There are several types of homologies including orthologs and paralogs. Orthologs are genes in different species that’ve evolved from a common ancestral gene by speciation, while paralogs result from duplication within an organism’s genome. In other words, orthologs retain the same function, whereas paralogs gain new functions [1]. Bellow is a Blast query which can reveal important sequence information and corresponding literature. Visit the National Center for Biotechnology webpage for more information.
Determining similar or homologous sequences through this online resource can be used to develop phylogenies, search for consensus sequences or compare with other genes. Performing multiple sequences alignments can show what sequences are relevant to the protein domains that interact with them. Software like Mega and Ensemble alignment tools can be used on any computer.
Results
Gene homology can be detected through the Basic Local Alignment Search Tool (BLAST) shown above. By comparison of nucleotide or amino acid sequences, their statistical similarity can be used to generate phylogeny trees and mutliple sequence alignments.
These sequence surrounds the 858 position of EGFR, which shows a high level of homology between mammalian organisms. This is concurrent with EGFR's prevelant function over the cell cycle, conserved in many vertebrates.
The next group of organism alignments occurs in the autophosphorylation domain which is important for EGFR dimers' catalytic activity. A less conserved sequence bellow Shows the very end of the aligned amino acid sequences. It seems that some areas of the protein are more conserved than others.
Discussion
Mice, one of the best model organisms to study Lung Adenocarcinoma, contain homologous Tyrosine Kinase domains, but for some reason the alignment was one base pair off. This may have some evolutionary relevance or could be an affect of Mega's implementation. Comparison with other alignment tools may determine this in the future. Knowing conserved DNA sequences can be useful when designing siRNA experiments that can knockout regular cell function. As shown bellow siRNAs can inhibit EGFR signaling illustrated on the right [3].
The tyrosine kinase domain is important for ERK, JAK-STAT and AKT signaling. This was shown to be important to cell growth and migration [3].
Shown bellow is the FASTA protein sequence may be useful for other online resources or software that requires the amino acid sequence. This may include NetPhos or PANTHER, both useful tools to uncover the functionality of EGFR
homologene-protein-sequence.fa |
References
1.) Julius H. Jackson, Terminologies for Gene & Protein Similarity, 1999. Retrieved from: https://msu.edu/~jhjacksn/Reports/similarity.htm
2.) Sara Barberán,1 José M. Martín-Durán, Evolution of the EGFR pathway in Metazoa and its diversification in the planarian Schmidtea mediterranea, 2016. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914847/
3.) Du, Yang, Genomic amplification and high expression of EGFR are key targetable oncogenic events in malignant peripheral nerve sheath tumor (2013). Retrieved from: https://www.researchgate.net/publication/259348317_Genomic_amplification_and_high_expression_of_EGFR_are_key_targetable_oncogenic_events_in_malignant_peripheral_nerve_sheath_tumor
2.) Sara Barberán,1 José M. Martín-Durán, Evolution of the EGFR pathway in Metazoa and its diversification in the planarian Schmidtea mediterranea, 2016. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914847/
3.) Du, Yang, Genomic amplification and high expression of EGFR are key targetable oncogenic events in malignant peripheral nerve sheath tumor (2013). Retrieved from: https://www.researchgate.net/publication/259348317_Genomic_amplification_and_high_expression_of_EGFR_are_key_targetable_oncogenic_events_in_malignant_peripheral_nerve_sheath_tumor