MBE Advance Access published online on September 21, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm198
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Research Article |
Neutrality, Compensation, and Negative Selection during Evolution of B-Cell Development Transcriptomes
1 Basel Institute for Immunology, Grenzacherstr. 487, 4005 Basel, Switzerland
2 Current address: Institute for Medical Miccrobiology and Immunology, technical University of Munich, Trogerstr. 30, 81675 Munich, Phone +49-89-4140-4155, Fax +49-89-4140-4933, Email: Reinhard.hoffmann(at)lrz.tum.de
3 Max Planck Institute for Molecular Genetics, Department of Computational Molecular Biology, Ihnestr. 73, 14195 Berlin, Germany
4 Current address: Institute for Functional Genomics, Computational Diagnostics, University of Regensburg, Josef-Engert-Str. 9, 93053 Regensburg, Germany
5 Universitäts-Kinderspital beider Basel, Dept. Hematology and Oncology, Römergasse 8, 4005 Basel, Switzerland
6 Current address: Universität Basel, Pharmazentrum, Dept. of Immunology, Klingelbergstr. 50-70, CH-4056 Basel, Switzerland
7 Current address: Max Planck Institute for Infection Biology, Schumannstr. 21-22, 10117 Berlin, Germany
8 These authors contributed equally to this work
* To whom correspondence should be addressed.
Received for publication March 19, 2007. Revision received August 8, 2007. Accepted for publication September 5, 2007.
B cells develop in the mammalian bone marrow through a sequence of precursor stages which can be ordered by the recombination status of their immunoglobulin loci. This developmental pathway is functionally similar between mice and man. However, whether this similarity is based on usage of the same genes is unknown. We show that large-scale gene expression patterns differ substantially between human and mouse B cell development. Among 644 genes which were differentially expressed in four early stages of human B cell development, only 48, 86, and 75 genes could be identified which are upregulated in both human and mouse Pre-BI, large Pre-BII, and small Pre-BII cells, respectively. A comparison of mouse B and T cell development reveals that gene expression patterns of early murine B- and T-cell precursors are most similar, while in more differentiated precursors, human and mouse B cells have a more similar gene expression profile. We conclude that large-scale differences in gene expression patterns between human and mouse B cell precursors may stem from either selective neutrality or compensatory evolution, while the few similarities may stem from negative selection. Gene expression patterns are shaped by ontogenic relationships in early and by functional specialization in later stages of development.
Key Words: transcriptomes • evolution • lymphocytes • Mus musculus • Homo sapiens