Evolution of Myb

    Three closely related Myb genes are present in vertebrate animals including mammals, birds, amphibians, and bony fish.  In the laboratory mouse, c-Myb is required for blood cell production in the embryo and for intestinal maintenance in adults, A-Myb is required for spermatogenesis and mammary gland proliferation, and B-Myb is required very early in embryonic development.  The invertebrate sea urchin and fruit fly each have a single Myb gene most closely related to B-Myb of vertebrates.  In particular, the A-Myb and c-Myb proteins contain a highly conserved central transcriptional activation domain not present in B-Myb or the Myb proteins of invertebrates (1).  In contrast, the corresponding region of B-Myb has continued to evolve rapidly (2). These results suggest that A-Myb and c-Myb arose by two gene duplications (red circles) that occurred after the emergence of the vertebrate lineage.  In support of this hypothesis, we have recently found that B-Myb, but neither A-Myb nor c-Myb, can complement the hemocyte defects in Drosophila Myb null mutant larvae (3).  Surprisingly, the intensively studied nematode worm C elegans appears to have lost the Myb gene during the course of evolution (4,5). 

 

Key to protein cartoons: blue boxes = tandem Myb repeats of DNA-binding domain; red boxes = transcriptional activation domain; green boxes = conserved C-terminal regulatory domain.

1. Ganter B, Lipsick JS. Myb and oncogenesis. Adv. Cancer Res. 76: 21-60 (1999).

2. Simon AL, Stone EA, Sidow A. Inference of functional regions in proteins by quantification of evolutionary constraints. Proc Natl Acad Sci U S A. 2002 99:2912-7 (2002).

3. Davidson CJ, Tirouvanziam R, Herzenberg LA, Lipsick JS. 2005. Functional evolution of the vertebrate Myb gene family: B-Myb, but neither A-Myb nor c-Myb, complements Drosophila Myb in hemocytes. Genetics 169: 215-229. [pdf].

4. Lipsick, JS. 2004. synMuv Verite-- Myb Comes Into Focus. Genes & Development 18: 2837-2844. [pdf]

5. Wen H, Andrejka L, Ashton J, Karess R, Lipsick JS. 2008. Epigenetic regulation of gene expression by Drosophila Myb and E2F2-RBF via the Myb-MuvB/dREAM complex.  Genes & Development 22: 601-614.