Gene duplication and loss is a powerful source of functional innovation. However, the general principles that govern this process are still largely unknown. With the growing number of sequenced genomes, it is now possible to examine these events in a comprehensive and unbiased manner. Here, we develop a procedure that resolves the evolutionary history of all genes in a large group of species. We apply our procedure to seventeen fungal genomes to create a genome-wide catalogue of gene trees that determine precise orthology and paralogy relations across these species. We show that gene duplication and loss is highly constrained by the functional properties and interacting partners of genes. In particular, stress-related genes exhibit many duplications and losses, whereas growth-related genes show selection against such changes. Whole-genome duplication circumvents this constraint and relaxes the dichotomy, resulting in an expanded functional scope of gene duplication. By characterizing the functional fate of duplicate genes we show that duplicated genes rarely diverge with respect to biochemical function, but typically diverge with respect to regulatory control. Surprisingly, paralogous modules of genes rarely arise, even after whole-genome duplication. Rather, gene duplication may drive the modularization of functional networks through specialization, thereby disentangling cellular systems.

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Abstract. The requirements of wide-area distributed database systems differ dramatically from those of local-area network systems. In a wide-area network (WAN) configuration, individual sites usually report to different system administrators, have different access and charging algorithms, install site-specific data type extensions, and have different constraints on servicing remote requests. Typical of the last point are production transaction environments, which are fully engaged during normal business hours, and cannot take on additional load. Finally, there may be many sites participating in a WAN distributed DBMS.In this world, a single program performing global query optimization using a cost-based optimizer will not work well. Cost-based optimization does not respond well to sitespecific type extension, access constraints, charging algorithms, and time-of-day constraints. Furthermore, traditional cost-based distributed optimizers do not scale well to a large number of possible processing sites. Since traditional distributed DBMSs have all used cost-based optimizers, they are not appropriate in a WAN environment, and a new architecture is required.We have proposed and implemented an economic paradigm as the solution to these issues in a new distributed DBMS called Mariposa. In this paper, we present the architecture and implementation of Mariposa and discuss early feedback on its operating characteristics.

Probability distributions are useful for expressing the meanings of probabilistic languages, which support formal modeling of and reasoning about uncertainty. Probability distributions form a monad, and the monadic definition leads to a simple, natural semantics for a stochastic lambda calculus, as well as simple, clean implementations of common queries. But the monadic implementation of the expectation query can be much less efficient than current best practices in probabilistic modeling. We therefore present a language of measure terms, which can not only denote discrete probability distributions but can also support the best known modeling techniques. We give a translation of stochastic lambda calculus into measure terms. Whether one translates into the probability monad or into measure terms, the results of the translations denote the same probability distribution.

Supplementary data are available at Bioinformatics online.

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