Assignment 2
 

Human carrier sequences that do not have a mouse ortholog 

Below is a numerical list of human sequences that need mouse orthologs.  
An ortholog is a gene that is equivalent in two different species by sharing the same 
common ancestor.  For example, this means that any gene in the common ancestor of mouse 
and human has been separated now by about 96 million years since the species diverged.  
The function of these genes is preserved and the sequence is probably very similar.  

Some genes have duplicated since the species diverged and one of these duplicated genes 
often takes on a new role.  The other keeps the original function.  These genes caused by 
duplication in a single species are called paralogs.  A paralog may not have an equivalent 
gene in the other species.  Below, 46A and 46B may be paralogs and there may only be one 
related sequence in mouse. 

Below there are 20 sequences in 15 groups.  Some groups contain more than one closely 
related member.  Depending on when these members duplicated, they may have mouse 
orthologs or they may not.  The numbers refer to the sequence alignment.

Your task is to find the mouse orthologs of the human genes.  You have to do this for 
two sequences, but doing more will help you learn more.  You will see that this excercise 
builds on the last one since you will have to extend your sequence to cover the full length of 
the new gene.  This will involve the same strategies you learned on the first assignment.
The difference in this task is that the new sequence is not a 100% match to the search sequence.  
You will have to estimate if the hit is an ortholog or just a related sequence.  The criteria to use 
Are percent identity, which should be high (85-97%) and blast searching against the human 
set of carriers on our local carrier blast server.  The new sequence should have a best match 
to a known carrier in humans and that will be the ortholog.  To get the human sequences
you will use for queries go to the link for human carriers under the module 3 page.

Return to me by email the accession numbers of the new sequences and an alignment with 
the human sequence you searched with.  Blast search your new sequence against the set of 
known mouse genes so you are sure it is new and not one of the known genes.
This can be done at the P450 blast server that has had the mouse and human carrier 
sequences added as two separate search options from the pull down menu.
Blast server for carriers and P450s 
The mouse sequences alignment has been updated to reflect the gap filling we have been doing.
revised alignment of carriers
The alignment to the best human match can also be done with this blast server.  Just cut and 
paste your result, making any additions needed at the ends, since the sequences may not 
match all the way to the ends.

I have already done the searching and found all the orthologs, so they do exist.
Good hunting.


44

46A and 46B (very similar, there may only be one mouse sequence like these)

50 human has five genes in this sequence group 50, 52, 52A, 52b and 55.
Mouse has 4 identified genes and there may be a fifth mouse sequence, or there may not. 

57 Graves antigen

62

73A and 73B very similar sequences.  There may be only one mouse seq.

78, 78A and 78B Human has three of these, mouse may have 1, 2 or 3 of them.

90B

96C

103 and 103A mouse probably has two genes related to both of these, since thay are not that 
similar to each other.

105

167 phosphate carrier.  Human has alternative splicing of exon 2.  Mouse may also have 
this alternative splicing.  Search with both exon two sequences from human.
Mouse 166 is only one aa (amino acid) different than human 165 in exon 2, but is about 12 
aa different from human 167 in this short exon.
Human exon 2 EYSCEFGSAKYYALCGFGGVLSCGLTHTAVVPLDLVKCRMQ

184

193 Human has 3 closely related UCP sequences UCP1, UCP2, and UCP3,
Mouse has two known genes and may have a third also.  UCP4 (184) human is not so 
similar to these three.

198