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10.2 Genome Architecture and Evolution   349


                       Figure 10.8  Domain architecture of transcription factors. Protein domains are indicated as colored icons labeled POZ, HD
                       (homeodomain), etc. Horizontal lines connect domains found in the same protein. The numbers and types of transcription factors vary
                       considerably between different species due to protein domain reshuffling during evolution. As an example, worms make about 143 different
                       transcription factors containing POZ domains, of which three are shown, while fruit flies make about 93 POZ-containing proteins, of which two
                       are shown. Some of the domains shown govern DNA binding, while others facilitate protein–protein interactions.
                                             Worm                       Fly                     Human
                                    POZ:~143  Homeodomain:~90  POZ:~95  Homeodomain:~92  POZ:~140  Homeodomain:~220
                                    MATH  POZ  Paired  HD  HD  POZ  C2H2  C2H2  Paired  HD  HD  POZ  C2H2  C2H2  C2H2  C2H2  C2H2  C2H2  Paired  HD  HD
                                    POZ  K    Pou  HD  Lim  HD          Pou  HD  Lim  HD            Pou  HD  Lim  HD
                                                               POZ  A                   POZ  bZip
                                      POZ
                                                NHR:~230       C4DM:~80 SAZ (MYB-like):~35  Krab:~220  Scan:~50
                                                  Zn  LB       C4DM  C2H2  C2H2  SAZ  SAZ  SAZ  Krab  C2H2  C2H2  C2H2  C2H2  C2H2  C2H2  Scan  C2H2  C2H2  C2H2  C2H2  C2H2  C2H2
                                                                      bHLH:~53                 bHLH:~105
                                                                bHIH    bHIH  PAS PAS      bHIH   bHIH  PAS PAS



                       Figure 10.9  Homeodomain consensus sequence. The consensus sequence of amino acids shows the most commonly found amino
                       acid at a given position within all known homeodomains in all organisms. Subsequent rows show matches to the consensus (purple) of
                       homeodomains in nine Drosophila proteins that dictate key aspects of the animal’s development. (These genes and proteins will be
                       discussed in Chapter 19.)
                               Consensus   R R RKR TAYT RYQL LELE KE FHFNRYL T RRRR IE LAHS LNL TE RQVK IWFQNR RHKWK KEN
                                    Ubx    R R RGRQT YT RYQT LELE KE FHTNHYLT RRRR IEMAHA LSL TE RQ IKI WFQNRRMKLK KE I
                                   Abd-A   R RRGRQT YT RFQT LELE KE FHFNHYL T RRRR IE I AHA LSL TE RQ IKI WFQNRRMKLK KE L
                                   Abd-B   VRKKRKPY SK FQT LELE KE FLFNAVS KQKRWI LMRNAQSL TE RV IKI WFQNRRMKNK KNS
                                     lab   NNSGR TNFTNKQL T ELE KE FHFNRYL T RRRR IE IANT LQLNE TQVK IWFQNR RMKWK KEN
                                     pb    P R RLR TAY TNTQL LELE KE FHTNKYLCRPR RI EI AAS LDL TE RQVKVWFQNRRMKHK RQT
                                     Dfd   P K RQR TAYT LHQI LELE KE FHYNRYLT RRRR IE IAHT LVL SE RQ IKI WFQNRRMKWK KDN
                                     Scr   T K RQR TS YT RYQT LELE KE FHFNRYL T RRRR IE I AHA LSL TE RQ IKI WFQNRRMKWK KEN
                                    Antp   R K RGRQT YT RYQT LELE KE FHFNRYL T RRRR IE I AHA LSL TE RQ IKI WFQNRRMKWK EI N



                       different purposes. Similarly, many genes are composed of     homeodomain-containing protein by comparing its puta-
                       multiple exons that encode discrete protein domains. The   tive amino acid sequence to those of known homeodomains
                       shuffling, addition, or deletion of exons during evolution   and searching for similarity (Fig. 10.9).
                       can create new genes whose protein products have novel   The mechanism of RNA splicing facilitates this kind
                       domain architectures (different numbers and kinds of do-  of exon rearrangement in eukaryotic genomes (and thus
                       mains in different orders) and thus can assume new roles in   the creation of new genes) because the reshuffling does
                       cells and organisms.                                not have to be precise. Suppose, as shown in Fig. 10.10,
                          Figure 10.8 shows an example of the domains associ-  that the exon of one gene plus its flanking introns is
                       ated with various transcription factors, proteins that bind   moved to a new location in the intron of a different gene.
                       to regions of DNA such as enhancers that control the tran-  This exon can now be spliced together with the second
                       scription of nearby genes. Exon shuffling over evolution   gene’s exons to make a single mRNA molecule, regard-
                       has produced different transcription factors with differing   less of where within the introns these pieces of DNA were
                       domains that enable these proteins to recognize particular   brought together.
                       DNA sequences and also to interact uniquely with cofac-
                       tors such as other proteins.
                          Biologists may guess at the function of a new protein   Gene families
                       (or the gene that encodes it) by analogy, if they find by   Gene families are groups of genes closely related in se-
                       computerized analysis that it contains a domain known to   quence  and function; such  gene families are abundant
                       play a specific role in other proteins. As an example, many   throughout genomes. Examples of gene families include
                       proteins that include a homeodomain (a particular DNA-  the genes that encode the hemoglobins that allow us to
                       binding motif) are transcription factors important for   transport oxygen in our blood (Fig. 10.11), the immunoglo-
                       the development of multicellular organisms. Computer   bins (antibodies) that help us ward off infections, and the
                         algorithms determine that a particular gene encodes a   olfactory receptors critical for our sense of smell.
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