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Eric S Haag

Publications and source records attributed to Eric S Haag.

10 recordsLinked to original sources
PubMed2006

Compensatory vs. pseudocompensatory evolution in molecular and developmental interactions.

The evolution of molecules, developmental circuits, and new species are all characterized by the accumulation of incompatibilities between ancestors and descendants. When specific interactions between components are necessary at any of these levels, this requires compensatory coevolution. Theoretical treatments of compensatory evolution that only consider the endpoints predict that it should be rare because intermediate states are deleterious. However, empirical data suggest that compensatory evolution is common at all levels of molecular interaction. A general solution to this paradox is provided by plausible neutral or nearly neutral intermediates that possess informational redundancy. These intermediates provide an evolutionary path between coadapted allelic combinations. Although they allow incompatible end points to evolve, at no point was a deleterious mutation ever in need of compensation. As a result, what appears to be compensatory evolution may often actually be "pseudocompensatory." Both theoretical and empirical studies indicate that pseudocompensation can speed the evolution of intergenic incompatibility, especially when driven by adaptation. However, under strong stabilizing selection the rate of pseudocompensatory evolution is still significant. Important examples of this process at work discussed here include the evolution of rRNA secondary structures, intra- and inter-protein interactions, and developmental genetic pathways. Future empirical work in this area should focus on comparing the details of intra- and intergenic interactions in closely related organisms.

Animals↗
PubMed2006

Genetic flexibility in the convergent evolution of hermaphroditism in Caenorhabditis nematodes.

The self-fertile hermaphrodites of C. elegans and C. briggsae evolved from female ancestors by acquiring limited spermatogenesis. Initiation of C. elegans hermaphrodite spermatogenesis requires germline translational repression of the female-promoting gene tra-2, which allows derepression of the three male-promoting fem genes. Cessation of hermaphrodite spermatogenesis requires fem-3 translational repression. We show that C. briggsae requires neither fem-2 nor fem-3 for hermaphrodite development, and that XO Cb-fem-2/3 animals are transformed into hermaphrodites, not females as in C. elegans. Exhaustive screens for Cb-tra-2 suppressors identified another 75 fem-like mutants, but all are self-fertile hermaphrodites rather than females. Control of hermaphrodite spermatogenesis therefore acts downstream of the fem genes in C. briggsae. The outwardly similar hermaphrodites of C. elegans and C. briggsae thus achieve self-fertility via intervention at different points in the core sex determination pathway. These findings are consistent with convergent evolution of hermaphroditism, which is marked by considerable developmental genetic flexibility.

Animals↗
PubMed2005

Intraspecific variation in fem-3 and tra-2, two rapidly coevolving nematode sex-determining genes.

The sex determination gene fem-3 encodes one of the most divergent proteins yet described in the terrestrial nematode Caenorhabditis. Despite this rapid sequence change, however, FEM-3 is essential for male development in the three species surveyed thus far. It also participates in conserved protein-protein complexes with the transmembrane receptor TRA-2 and the phosphatase FEM-2 in these species. These interactions show strong species specificity, indicating that conserved residues are not sufficient for function and that compensatory evolution between binding partners is important. To shed further light on the nature of this coevolution, and to discern the extent of amino acid polymorphism allowed in FEM-3 and the domain of TRA-2 that binds it, we have examined intraspecific variation in the gonochoristic species Caenorhabditis remanei. Ten new complete Cr-fem-3 alleles from three regions of the United States are described. We also obtained sequences for the FEM-3-binding domain of TRA-2 for 9 of the same strains. These alleles were compared with each other, with the European founder alleles, and with the orthologous sequences from the congeners Caenorhabditis elegans and C. briggsae. We find that FEM-3 harbors abundant amino acid polymorphisms along its entire length. The majority (but not all) of these occur in nonconserved residues, and in at least one domain there is evidence for diversifying selection. The FEM-3-binding domain of TRA-2 is less polymorphic than FEM-3. Amino acids neither polymorphic nor conserved between species are candidates for residues mediating species-specific interaction of FEM-3 with its binding partners.

Alleles↗
PubMed2005

Compensatory evolution of interacting gene products through multifunctional intermediates.

When two mutations are singly deleterious but neutral or beneficial together, compensatory evolution can occur. The accumulation of derived, compensated genotypes contributes to the evolution of genetic incompatibilities between diverging populations or species. Previous two locus/two allele models have shown that compensatory evolution is appreciable only with tight linkage, the possibility of nearly simultaneous mutations, and/or a way to overcome negative selection against the singly mutated genotype. These conditions are often not met. Even when they are met, compensatory evolution is still predicted to be extremely slow, and in many scenarios selective advantage of the compensated genotype does little to accelerate it. Despite these obstacles, empirical studies suggest that it occurs readily. We describe here a set of related two locus/three allele models that invoke plausible neutral intermediates capable of productive interaction with both ancestral and compensated products of the interacting locus. These models are explored with analytical and computer simulation methods. The effect of these stepping-stone alleles on the evolution of ancestor-descendant incompatibilities is often profound, making the difference between evolution and stasis in several situations, including in small populations, when codominance or haploidy prevents shielding of mismatched genotypes, and in the absence of positive selection on the derived genotype. However, in large populations these intermediates can either speed or slow the evolution of incompatible genotypes relative to the two-allele case, depending on the specific fitness model. These results suggest that population size, the source of adaptive benefit, and the structural details of heteromeric gene product complexes interact to influence the path by which intergenic incompatibility evolves.

Computer Simulation↗
PubMed2004

Germline imprinting: battle of the sexes or battle of the X's?

The X chromosome is largely inactivated in spermatogenesis of heterogametic males, and in multiple phyla it encodes few genes specifically expressed in the male germline. Writing in Nature Genetics, Bean et al. report a parallel between male germline X inactivation in nematodes and a fungal gene-silencing mechanism that alters the way we view the evolution of both phenomena.

Animals↗
PubMed2002

Rapid coevolution of the nematode sex-determining genes fem-3 and tra-2.

Unlike many features of metazoan development, sex determination is not widely conserved among phyla. However, the recent demonstration that one gene family controls sexual development in Drosophila, C. elegans, and vertebrates suggests that sex determination mechanisms may have evolved from a common pathway that has diverged radically since the Cambrian. Sex determination gene sequences often evolve quickly, but it is not known how this relates to higher-order pathways or what selective or neutral forces are driving it. In such a rapidly evolving developmental pathway, the fate of functionally linked genes is of particular interest. To investigate a pair of such genes, we cloned orthologs of the key C. elegans male-promoting gene fem-3 from two sister species, C. briggsae and C. remanei. We employed RNA interference to show that in all three species, the male-promoting function of fem-3 and its epistatic relationship with its female-promoting upstream repressor, tra-2, are conserved. Consistent with this, the FEM-3 protein interacts with TRA-2 in each species, but in a strictly species-specific manner. Because FEM-3 is the most divergent protein yet described in Caenorhabditis and the FEM-3 binding domain of TRA-2 is itself hypervariable, a key protein-protein interaction is rapidly evolving in concert. Extrapolation of this result to larger phylogenetic scales helps explain the dissimilarity of the sex determination systems across phyla.

Amino Acid Sequence↗