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Background  The functional repertoire of the human proteome is an incremental collection of functions accomplished by protein domains evolved along the  Homo sapiens  lineage. Therefore, knowledge on the origin of these functionalities provides a better understanding of the domain and protein evolution in human. The lack of proper comprehension about such origin has impelled us to study the evolutionary origin of human proteome in a unique way as detailed in this study.    Results  This study reports a unique approach for understanding the evolution of human proteome by tracing the origin of its constituting domains hierarchically, along the  Homo sapiens  lineage. The uniqueness of this method lies in subtractive searching of functional and conserved domains in the human proteome resulting in higher efficiency of detecting their origins. From these analyses the nature of protein evolution and trends in domain evolution can be observed in the context of the entire human proteome data. The method adopted here also helps delineate the degree of divergence of functional families occurred during the course of evolution.    Conclusion  This approach to trace the evolutionary origin of functional domains in the human proteome facilitates better understanding of their functional versatility as well as provides insights into the functionality of hypothetical proteins present in the human proteome. This work elucidates the origin of functional and conserved domains in human proteins, their distribution along the  Homo sapiens  lineage, occurrence frequency of different domain combinations and proteome-wide patterns of their distribution, providing insights into the evolutionary solution to the increased complexity of the human proteome.

Tracing the origin of functional and conserved domains in the human proteome: implications for protein evolution at the modular level.