Multipe Sequence Alignments:
Probing of the Twilight Zone
Solution




  1. Identifying a conserved domain

    • The only sequence having some similarity with XRC1_HUMAN is Rad4_schpo

    • The dotter indicates that there could be three homologous segments
    • In order to convince ourselves that these three segments are truly homologous, we can extract them and align them:[aln]
    • Conclusion:Among these three very diverse sequences, enough positions are completely conserved for us to conclude on the homology of these three domains.

  2. Identifying remote homologues

    • To identify more remote homologues, use the NCBI psi-blast
    • After two iterations, using XRC1_HUMAN, Liagses appear below the threshold[result]
    • The question is to know whether these alignments mean that XRC1_HUMAN is homologous to the ligases
    • The best way to establish that homology is to extract sequences from the Blast output and to make a multiple alignment[final_aln]
    • Conclusion:Despite the divergeance among the sequences that consitute this alignment several positions are highly conserved. This indicates a potential homology.

  3. Conclusion

    • XCR1_HUMAN seems to be a good candidate for being involved in DNA repairing mechanisms.
    • Thanks to the results given by the multiple alignment, we checked the five extra-sequences in psi-blast and re-ran it: [results]
    • This time a gene associated with breast cancer appears: BRCA1. However, it is difficult to include that sequence in a meaningful multiple sequence alignment.

    • In order to go further,one would need to build a profile and repeat the scanning made with psi-blast in a more controled maneer.

Questions should be sent to C.Notredame