This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
Summary of phylogenies with ligand binding sequence of AR and nhr-69
Using www.phylogeny.fr, I was able to align the ligand binding domain sequences found with SMART for AR and the nhr-69 homolog. I decided to run this analysis because the ligand binding domain accounts for many partial and mild forms of AIS. If the regions are similar, then it shows that the most variable region in the gene is still quite conserved, suggesting a strong selective force.
In figure 1, the zebra fish is more related to the mammalian species included than the chicken. This result appears to be counter to what should be seen and is seen in figure 2. Mammilian species are more related to birds than to fish as we share a more recent common ancestor with them. Figure 2 shows exactly that as well as showing that nhr-69, which is the C elegan homolog, as being very distantly related to all veterbrate species included. However, figure 3 shows humans as being more distantly related to other vertebrates than C elegans. This result is clearly wrong. This erroneous finding could be due to the size difference between nhr-69 and any of the androgen receptor genes. Mutliple likely alignments could be calculated giving different results.
You will notice that the chimpanzee was not included in this analysis. The chimpanzee, as was seen before has too short of a sequence to predict a ligand binding domain. It seems incredibly unlikely that our closest living relative does not have an extremely similar ligand binding domain to ours.
The phylogenies here and on Phylogeny: whole protein suggest that there is a strong selective force to conserve this gene as it determines sexual dimorphism and fertility. Few individuals with mild AIS are able or will reproduce in their lifetimes. With the more severe cases, they are almost always infertile. Mutations in the gene should happen through de novo mechanisms rather than through evolutionary events. The fact that the region accounting for most all cases of AIS has a large conservation with distantly related species, even the nhr-69 homolog, suggests that this gene is well conserved. This assertion establishes that many animal models could be used to study AIS in all of its forms without much difference in the gene or pathway.
In figure 1, the zebra fish is more related to the mammalian species included than the chicken. This result appears to be counter to what should be seen and is seen in figure 2. Mammilian species are more related to birds than to fish as we share a more recent common ancestor with them. Figure 2 shows exactly that as well as showing that nhr-69, which is the C elegan homolog, as being very distantly related to all veterbrate species included. However, figure 3 shows humans as being more distantly related to other vertebrates than C elegans. This result is clearly wrong. This erroneous finding could be due to the size difference between nhr-69 and any of the androgen receptor genes. Mutliple likely alignments could be calculated giving different results.
You will notice that the chimpanzee was not included in this analysis. The chimpanzee, as was seen before has too short of a sequence to predict a ligand binding domain. It seems incredibly unlikely that our closest living relative does not have an extremely similar ligand binding domain to ours.
The phylogenies here and on Phylogeny: whole protein suggest that there is a strong selective force to conserve this gene as it determines sexual dimorphism and fertility. Few individuals with mild AIS are able or will reproduce in their lifetimes. With the more severe cases, they are almost always infertile. Mutations in the gene should happen through de novo mechanisms rather than through evolutionary events. The fact that the region accounting for most all cases of AIS has a large conservation with distantly related species, even the nhr-69 homolog, suggests that this gene is well conserved. This assertion establishes that many animal models could be used to study AIS in all of its forms without much difference in the gene or pathway.
Figure 1: Generated with PhyML using an alignment from t-coffee
Figure 2: Generated with BioNJ using an alignment from t-coffee
Figure 3: Generated with TNT using an alignmet from t-coffee
Figure 4: Alignment with t-coffee for the ligand domain for the androgen receptor and nhr-69 (C. elegan homolog)
| alignment_with_t-coffee_ligand.pdf | |
| File Size: | 20 kb |
| File Type: | |
Website authored by Sam Trammell. Email: [email protected]. Last updated: May 13, 2009.
