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Background: With the advent of sequence-based approaches in the mutagenesis studies, it is now possible to directly evaluate the genome-wide pattern of experimentally induced DNA sequence changes for a diverse array of organisms. To gain a more comprehensive understanding of the mutational bias inherent in mouse ENU mutagenesis, this study describes a detailed evaluation of the induced mutational pattern obtained from a sequence-based screen of ENU-mutagenized mice.

Sexual communication in many moths occurs between females emitting a sex pheromone and males responding to it. Females of Ostrinia scapulalis (Lepidoptera: Crambidae) show a large variation in blend ratios of the two sex pheromone components (E)-and (Z)-11-tetradecenyl acetates. E type females produce a pheromone with a high percentage of (E)-11-tetradecenyl acetate, whereas Z type females produce the opposite blend. We established laboratory cultures of E and Z types. Females of the F 1 generation produced an intermediate blend (I type) in both reciprocal crosses of the E and Z cultures. Results of further crossing experiments suggested that the three pheromone types are primarily controlled by a single autosomal locus with two alleles. Also, analyses of the variation in pheromone blend within F 1 , backcross and F 2 families suggested that other genetic factors modify the pheromone blend of the I and Z types. Investigation of the pheromone variation in natural populations at 14 localities in Japan has shown that the E type was predominant in northern Japan, whereas the pheromone was highly polymorphic in central Japan. At a locality in central Japan, the pheromone was constantly polymorphic for several years, and the pheromone type frequencies did not deviate from Hardy-Weinberg expectations, providing no evidence of selection or assortative mating between the pheromone types. Analyses of pheromone variation within families derived from feral females indicated that matings between a pair with different genotypes for pheromone production was occurring in natural populations. Overall, this study showed that the genetic basis of the pheromone variation in O. scapulalis is very similar to that in its sibling species Ostrinia nubilalis although the state of pheromone polymorphisms in natural populations appears to differ between the two species.

Because distant species often share similar macromolecules, regulatory mutations are often considered responsible for much of their biological differences. Recently, a large portion of regulatory changes has been attributed to cis-regulatory mutations. Here, we examined an alternative possibility that the putative contribution of cis-regulatory changes was, in fact, caused by compensatory action of cis-and trans-regulatory elements. First, we show by stochastic simulations that compensatory cis-trans evolution maintains the binding affinity of a transcription factor at a constant level, thereby spuriously exaggerating the contribution of cis-regulatory mutations to gene expression divergence. This exaggeration was not observed when changes in the binding affinity were compensated by variable transcription factor concentration. Second, using reciprocal introgressions of Drosophila, we show that relative expression of heterozygous alleles from two distinct species often varied significantly between different species backgrounds, indicating the possible action of cis-trans compensation. Taken together, we propose that cis-trans hybrid incompatibilities are accumulating much faster than generally considered. compensatory evolution | trans-regulatory mutation | epistasis | cis-trans interaction | reproductive isolation A first step to understanding the evolution of gene expression is to decompose expression variation into cis-and transregulatory components (1-4). This decomposition can be done by combining an allele-specific expression assay using F 1 hybrids with expression assays in pure species backgrounds (1, 4). From these assays, two kinds of expression differences are determined for a gene: (i) difference between two parental strains and (ii) difference between two alleles in an F 1 hybrid. When the difference between parental strains is entirely due to trans-regulatory changes, we would not expect any difference between the two alleles in the hybrid condition. However, when the difference between parental strains is entirely due to cis-regulatory changes, this difference should be reproduced as an allelic difference in the hybrid. A recent application of this method identified a greater contribution of cis-regulatory changes in inter-than intraspecific comparisons, suggesting that cis-regulatory mutations are fixed more preferentially during evolution than transregulatory mutations (5).In the above decomposition, allelic differences in F 1 hybrids are entirely attributed to cis-regulatory variation under the assumption that trans-regulatory factors should affect both alleles equally. However, some types of cis-trans interactions can violate this assumption by differently affecting the two alleles. For example, by adapting to an evolving cis-regulatory element of the same species, a transcription factor may bind less efficiently with the cis-regulatory element from the distinct species. In the extreme case where the binding between species does not occur at all, an allelic difference in a hybrid would be simil...