Transcription Factor Expression in Lymphocyte Development: Clues to the Evolutionary Origins of Lymphoid Cell Lineages?

Abstract

Lymphocyte development provides an excellent model system for studying the evolutionary divergence of cell lineages. Based on their appearance in vertebrate phylogeny, the origins of lymphoid cell lineages are likely to lie in events which occurred during a defined range of time at least 450 million years ago. The dramatic emergence of both B cells and T cells in the cartilaginous fish (Litman et al. 1999) indicates the occurrence of at least one major event pivotal for the development of lymphocytes as we know them, after the divergence of the vertebrates from the other chordates but before the diversification of the jawed vertebrates. One such event may have been the acquisition, perhaps by horizontal transfer, of the recombination-activating genes (RAGs; Agrawal et al. 1998). The large-scale gene duplication events which are believed to have occurred at approximately this same time (Holland et al. 1994; Pebusque et al. 1998) may have provided another powerful mechanism for rapid evolutionary change. Lymphoid development is dependent upon networks of transcription factors, which serve not only to activate a series of temporally controlled gene batteries during differentiation but also to stabilize the mature phenotype. These transcription factors are generally members of multigene families whose origins are far more ancient than the lymphoid lineages in which they operate and provide a bridge across phylogenetic distances which have been thus far inaccessible to the study of rearranging antigen receptors. Furthermore, it is likely that duplication and/or divergence of both the cis-regulatory regions and the structural portions of transcription factor family members has contributed to the diversification of hematopoietic cell types in vertebrates.