The resolution of sexual antagonism by gene duplication

Disruptive selection between males and females can generate sexual antagonism, where alleles improving fitness in one sex reduce fitness in the other. This type of genetic conflict arises because males and females carry nearly identical sets of genes: opposing selection, followed by genetic mixing during reproduction, generates a population genetic "tug-of-war" that constrains adaptation in either sex. Recent verbal models suggest that gene duplication and sex-specific cooption of paralogs might resolve sexual antagonism and facilitate evolutionary divergence between the sexes. However, this intuitive proximal solution for sexual dimorphism potentially belies a complex interaction between mutation, genetic drift, and positive selection during duplicate fixation and sex-specific paralog differentiation. The interaction of these processes--within the explicit context of duplication and sexual antagonism--has yet to be formally described by population genetics theory. Here, we develop and analyze models of gene duplication and sex-specific differentiation between paralogs. We show that sexual antagonism can favor the fixation and maintenance of gene duplicates, eventually leading to the evolution of sexually dimorphic genetic architectures for male and female traits. The timescale for these evolutionary transitions is sensitive to a suite of genetic and demographic variables, including allelic dominance, recombination, sex linkage, and population size. Interestingly, we find that female-beneficial duplicates preferentially accumulate on the X chromosome, whereas male-beneficial duplicates are biased toward autosomes, independent of the dominance parameters of sexually antagonistic alleles. Although this result differs from previous models of sexual antagonism, it is consistent with several findings from the empirical genomics literature.     

Duplicate gene evolution and expression in the wake of vertebrate allopolyploidization

Background  

The mechanism by which duplicate genes originate – whether by duplication of a whole genome or of a genomic segment – influences their genetic fates. To study events that trigger duplicate gene persistence after whole genome duplication in vertebrates, we have analyzed molecular evolution and expression of hundreds of persistent duplicate gene pairs in allopolyploid clawed frogs (Xenopus and Silurana). We collected comparative data that allowed us to tease apart the molecular events that occurred soon after duplication from those that occurred later on. We also quantified expression profile divergence of hundreds of paralogs during development and in different tissues.     

Regulation of GATA gene expression during vertebrate development

GATA factors regulate critical events in hematopoietic lineages (GATA-1/2/3), the heart and gut (GATA-4/5/6) and various other tissues. Transgenic approaches have revealed that GATA genes are regulated in a modular fashion by sets of enhancers that govern distinct temporal and/or spatial facets of the overall expression patterns. Efforts are underway to resolve how these GATA gene enhancers are themselves regulated in order to elucidate the genetic and molecular hierarchies that govern GATA expression in particular developmental contexts. These enhancers also afford a raft of tools that can be used to selectively perturb and probe various developmental events in transgenic animals.     

Evolutionary inevitability of sexual antagonism

Sexual antagonism, whereby mutations are favourable in one sex and disfavourable in the other, is common in natural populations, yet the root causes of sexual antagonism are rarely considered in evolutionary theories of adaptation. Here, we explore the evolutionary consequences of sex-differential selection and genotype-by-sex interactions for adaptation in species with separate sexes. We show that sexual antagonism emerges naturally from sex differences in the direction of selection on phenotypes expressed by both sexes or from sex-by-genotype interactions affecting the expression of such phenotypes. Moreover, modest sex differences in selection or genotype-by-sex effects profoundly influence the long-term evolutionary trajectories of populations with separate sexes, as these conditions trigger the evolution of strong sexual antagonism as a by-product of adaptively driven evolutionary change. The theory demonstrates that sexual antagonism is an inescapable by-product of adaptation in species with separate sexes, whether or not selection favours evolutionary divergence between males and females.     

Differential expression of the cellular src gene during vertebrate development

Cellular genes that are homologous to the transforming genes of certain RNA tumor viruses are suspected to play a functional role during normal developmental processes. To investigate this further, we are studying the expression of the cellular homolog of the Rous sarcoma virus transforming gene (c-src) during embryogenesis of fish, frog, and chicken by quantitative determination of the activity of the c-src encoded protein kinase (pp60^c-src). The kinase activity from embryos of fish, frog, and chicken displays the same enzymatic characteristics as the kinase from adult animals: It phosphorylates only tyrosine residues in protein substrates, and its activity is relatively insensitive to inhibition by the diadenosine nucleotide Ap4A. During the course of development, the varying kinase activity level reflects differential expression of the c-src gene product. The kinase activity is low during early development, increases dramatically during organogenesis, and decreases thereafter to the level found in adult animals. The kinase activity displays an organ specificity, with brain showing the highest activity in embryos as well as in adults. Muscle, however, shows high activities during organogenesis, but no or barely detectable activity in adult animals. Our data suggest, therefore, that the c-src gene product plays more of a role in differentiation than in proliferation processes during embryogenesis, and that it may act as a pleiotropic effector.     

Electrical activity and gene expression in the development of vertebrate neural circuits.

Over the past several decades, anatomical and electrophysiological analyses have demonstrated that the electrical activity of neurons is required for development of the precise patterns of synaptic connectivity found in the adult central nervous system. However, knowledge of the molecular cascades that underlie activity-dependent synaptic development remains rudimentary. As a result, many fundamental issues remain unresolved. Recent advances in differential cloning have begun to provide the tools and insight necessary to bring a molecular level of understanding to principles of activity-dependent synaptic development established via classic systems approaches.     

Evolution and differential expression of a vertebrate vitellogenin gene cluster

Background  

The multiplicity or loss of the vitellogenin (vtg) gene family in vertebrates has been argued to have broad implications for the mode of reproduction (placental or non-placental), cleavage pattern (meroblastic or holoblastic) and character of the egg (pelagic or benthic). Earlier proposals for the existence of three forms of vertebrate vtgs present conflicting models for their origin and subsequent duplication.     

Another gene affecting sexual expression of Escherichia coli

We have examined the relationship between two chromosomal mutations of Escherichia coli K-12, fexA (0 min) and fexB (85 min), in regulating expression of the F sex factor. Together, fexA and fexB exert a pleiotropic effect on the expression of the F tra genes. F pilus synthesis, conjugal donor activity, and surface exclusion activity are all inhibited in the fexA fexB mutant. Either fex mutation alone is cryptic.     

Hox gene expression patterns in Lethenteron japonicum embryos--insights into the evolution of the vertebrate Hox code

The Hox code of jawed vertebrates is characterized by the colinear and rostrocaudally nested expression of Hox genes in pharyngeal arches, hindbrain, somites, and limb/fin buds. To gain insights into the evolutionary path leading to the gnathostome Hox code, we have systematically analyzed the expression pattern of the Hox gene complement in an agnathan species, Lethenteron japonicum (Lj). We have isolated 15 LjHox genes and assigned them to paralogue groups (PG) 1-11, based on their deduced amino acid sequences. LjHox expression during development displayed gnathostome-like spatial patterns with respect to the PG numbers. Specifically, lamprey PG1-3 showed homologous expression patterns in the rostral hindbrain and pharyngeal arches to their gnathostome counterparts. Moreover, PG9-11 genes were expressed specifically in the tailbud, implying its posteriorizing activity as those in gnathostomes. We conclude that these gnathostome-like colinear spatial patterns of LjHox gene expression can be regarded as one of the features already established in the common ancestor of living vertebrates. In contrast, we did not find evidence for temporal colinearity in the onset of LjHox expression. The genomic and developmental characteristics of Hox genes from different chordate species are also compared, focusing on evolution of the complex body plan of vertebrates.     

Changes in gene expression patterns during the sexual life cycle of Chlamydomonas reinhardtii

Significant differences in membrane fluidities, expressed as fluorescence anisotropies, are demonstrated between embryogenic (E) and non-embryogenic (NE) cell lines when cells in suspension culture are removed from auxin. Cells of an E and NE cell line of Asclepias tuberosa were grown for 21 days either with or without 2, 4-dichlorophenoxy acetic acid (2,4-D), cultures were sampled at various intervals and protoplast membrane (hydrophobic interiors) was labeled with 1, 6 diphenyl-1, 3, 5-hexatriene (DPH). No differences between cultures with and without 2,4-D were detected in the NE line. In contrast the E line rapidly developed differences in membrane fluidity over time. Such clear differences in the responses of E and NE lines in membrane fluidity indicated that this parameter could be a good predictor and marker for embryogenesis. Eight suspension cell lines of Asclepias and 2 of Daucus carota were tested. After 2 days on medium without auxin, every E cell line exhibited a positive change in anisotropy and became embryogenic, whereas NE cell lines exhibited much lower positive changes or even negative changes in anisotropy and never underwent embryogenesis. Such changes have been consistent in all cell lines tested and represent a marker for embryogenicity in suspension cell lines before morphological change becomes apparent after removal from auxin. Basic molecular membrane changes in embryogenesis are likely to be common among different culture systems and understanding them could be a major step in removing barriers to regenerating plants from cultured material.     

Strategies for exploration of freeze responsive gene expression: advances in vertebrate freeze tolerance

Winter survival for many cold-blooded species involves freeze tolerance, the capacity to endure the freezing of a high percentage of total body water as extracellular ice. The wood frog (Rana sylvatica) is the primary model animal used for studies of vertebrate freeze tolerance and current studies in my lab are focused on the freeze-induced changes in gene expression that support freezing survival. Using cDNA library screening, we have documented the freeze-induced up-regulation of a number of genes in wood frogs including both identifiable genes (fibrinogen, ATP/ADP translocase, and mitochondrial inorganic phosphate carrier) and novel proteins (FR10, FR47, and Li16). All three novel proteins share in common the presence of hydrophobic regions that may indicate that they have an association with membranes, but apart from that each shows unique tissue distribution patterns, stimulation by different signal transduction pathways and responses to two of the component stresses of freezing, anoxia, and dehydration. The new application of cDNA array screening technology is opening up a whole new world of possibilities in the search for molecular mechanisms that underlie freezing survival. Array screening of hearts from control versus frozen frogs hints at the up-regulation of adenosine receptor signaling for the possible mediation of metabolic rate suppression, hypoxia inducible factor mediated adjustments of anaerobic metabolism, natriuretic peptide regulation of fluid dynamics, enhanced glucose transporter capacity for cryoprotectant accumulation, defenses against the accumulation of advanced glycation end products, and improved antioxidant defenses as novel parts of natural freeze tolerance that remain to be explored.     

Molecular evolution of the vertebrate hexokinase gene family: Identification of a conserved fifth vertebrate hexokinase gene

Hexokinases (HK) phosphorylate sugar immediately upon its entry into cells allowing these sugars to be metabolized. A total of four hexokinases have been characterized in a diversity of vertebrates—HKI, HKII, HKIII, and HKIV. HKIV is often called glucokinase (GCK) and has half the molecular weight of the other hexokinases, as it only has one hexokinase domain, while other vertebrate HKs have two. Differing hypothesis has been proposed to explain the diversification of the hexokinase gene family. We used a genomic approach to characterize hexokinase genes in a diverse array of vertebrate species and close relatives. Surprisingly we identified a fifth hexokinase-like gene, HKDC1 that exists and is expressed in diverse vertebrates. Analysis of the amino acid sequence of HKDC1 suggests that it may function as a hexokinase. To understand the evolution of the vertebrate hexokinase gene family we established a phylogeny of the hexokinase domain in all of the vertebrate hexokinase genes, as well as hexokinase genes from close relatives of the vertebrates. Our phylogeny demonstrates that duplication of the hexokinase domain, yielding a HK with two hexokinase domains, occurred prior to the diversification of the hexokinase gene family. We also establish that GCK evolved from a two hexokinase domain-containing gene, but has lost its N-terminal hexokinase domain. We also show that parallel changes in enzymatic function of HKI and HKIII have occurred.