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Biomedical subjects

W M Lewis

Publications and source records attributed to W M Lewis.

10 recordsLinked to original sources

Drosophila rab GDI mutants disrupt development but have normal Rab membrane extraction.

Rab GTPases are essential for vesicular transport. Rab GDP dissociation inhibitor (GDI) binds to GDP-bound rabs, removes rabs from acceptor membranes and delivers rabs to donor membranes. We isolated lethal GDI mutations in Drosophila and analyzed their developmental phenotypes. To learn how these mutations affect GDI structure, the crystal structure of Drosophila GDI was determined by molecular replacement to a resolution of 3.0 A. Two hypomorphic, missense mutations are located in domain II of GDI at highly conserved positions, but not in previously identified sequence conserved regions. The mutant GDIs were tested for ability to extract rabs from membranes and showed wild-type levels of rab membrane extraction. The two missense alleles showed intragenic complementation, indicating that domain II of GDI may have two separable functions. This study indicates that GDI function is essential for development of a complex, multicellular organism and that puparium formation and pole cell formation are especially dependent on GDI function.

Alleles↗

The cost of sex.

The potential costs of sex can be divided into two large categories. The first category consists of costs that are not derived from anisogamy, and includes costs associated with recombination, with delay of synthesis at the cellular level (cellular-mechanical cost), and with fertilization. The second large category of costs is derived from anisogamy. Specific costs include the cost of genome dilution (cost of males) and the cost of sexual selection. The cost of genome dilution applies to sexual females in anisogamous organisms because the female provides cytoplasm and reserve materials to support the male genome as well as her own genome. The cost of sexual selection is caused by loss of fitness through selection resulting from sexual competition, or through dual phenotypic specialization of a single species as a result of sexual selection. All factors contributing to the cost of sex apply potentially to a broad spectrum of organisms. However, numerous mechanisms reduce the realized cost of sex to a level far below the potential cost. The potential cost is likely to be highest in small organisms, but the realized cost among these organisms is reduced greatly by intermittent sexuality. The realized cost of sex tends to increase with size and complexity among organisms because of increasing commitment to sex with increasing size. Increasing commitment to sex is required by the lower reproductive rates and consequently lower rates of adaptation in larger organisms, which would put such organisms at a disadvantage in relation to smaller organisms were it not for increasing commitment to sexual recombination in larger organisms. Comparable commitment to sex is not possible in smaller organisms because such organisms have a higher potential cost of sex, which maintains among them a lower limit on the frequency of sex.

Animals↗