Comparison of two zinc finger proteins

We compare two zinc finger proteins from Mus musculus. We use the mRNA sequences for Zfp111 and Zfp235 [SHGBS]. These two proteins have a similar amino acid sequences: one KRAB domain, followed by a spacer region, followed by a series of zinc finger domains in tandem. The members of this protein family each have from five to nineteen of the 28 amino acid zinc finger domains. Most of these amino acids are required for zinc binding, and are highly conserved between duplications and between genes. Shannon et al. show statistically that over all nucleotide positions in the zinc finger domains, substitution events tend to be synonymous. They observe a range of selection behaviors at positions believed to be noncritical to the zinc binding function.

Figure: Comparison of zinc finger protein mRNA seqences for Mus musculus Zfp111 and Zfp235. The normalized likelihood array $W$ shows: high sequence identity to coordinate (537, 540), then a mismatch with a net insertion of 222 bases in Zfp235. In the rectangle with bottom left corner (622, 844) and top right corner (2106, 2112), there are many parallel tracks, with parts of three more intense than the others.

Figure 4 shows the $W$ array computed with the Zfp111 and Zfp235 sequences. The $W$ array shows high sequence identity at the beginning of the sequence, followed by a mismatch with a net insertion in the Zfp235 sequence.

Figure 5: Difference plot $\Delta W$ from comparison of Zfp111 and Zfp235. The $\Delta W$ array suggests there is high sequence identity between bases 547 through 621 of Zfp111 and 722 through 843 of Zfp235 relative to any potential alignment of these two sequences, by the narrow black and white diamond at these coordinates. Above and to the right of coordinate (622, 844), the parallel tracks suggest near-repeat subsequences and the black and white diamonds indicate the more similar regions. The diamonds which cover the same vertical coordinates, near coordinates 1300 and 1800 of Zfp235, suggest sequence duplication within Zfp111.

Figure 5 shows the $\Delta W$ plot for the same sequences and parameters. The $\Delta W$ plot provides more detail on the mismatch discovered by the $W$ array plot. We see insertion of the second Zfp235 zinc finger relative to Zfp111 and insertion of either the eighth or ninth Zfp111 zinc finger relative to Zfp235.

Figure 6 shows a detail of the same $\Delta W$ array. We can locate a single amino acid deletion in Zfp111 relative to Zfp235.

Figure 6: Detail of $\Delta W$ showing single amino acid deletion of either the sixth or seventh amino acid of the fifth zinc finger in Zfp111.

Figure 7: The $\Delta W$ array of Zfp111 compared with itself. The black and white diamonds off the large one, centered near coordinates $(700,1100)$ and $(1100, 700)$ strongly suggest internal duplication.

Zinc fingers 10 through 13 of Zfp235 match zinc fingers 10 through 13 and also zinc fingers 14 through 17 of Zfp111. Figure 7, showing the $\Delta W$ array for Zfp111 against itself, provides strong evidence of the internal duplication in Zfp111.