Were Workers of Eusocial Hymenoptera Initially Altruistic or Oppressed?

Studies of a primitively eusocial halictid bee, Lasioglossum zephyrum, strongly suggest that a major factor in originating a worker caste is selection at the individual level for queens that control associated adult females. Even in this scarcely social form, the queen inhibits other adult females from becoming queens, perhaps by her high level of activity and frequent nudging in the nest. Queens are behaviorally less varied than workers and show specialization, particularly in frequency of nudging (which is concentrated on the worker with largest ovaries) and of backing. Backing draws workers, especially those with slender ovaries, down to lower parts of the burrows where the stimuli for cell construction and provisioning probably operate. Eating of worker-laid eggs by queens was also noted. In spite of the suggestion that queens have evolved to control their workers rather than that workers have evolved to help their queens, both may well have occurred, for these processes are not mutually exclusive; moreover, social attributes mutually beneficial to both castes no doubt have arisen.     

Nonrelatives inherit colony resources in a primitive termite

The evolution of eusociality, especially how selection would favor sterility or subfertility of most individuals within a highly social colony, is an unresolved paradox. Eusociality evolved independently in diverse taxa, including insects (all ants and termites; some bees, wasps, thrips, and beetles), snapping shrimp, and naked mole rats. Termites have received comparatively less focus than the haplodiploid Hymenoptera (ants, bees, and wasps); however, they are the only diploid group with highly complex colonies and an extraordinary diversity of castes. In this study we staged encounters between unrelated colonies of primitive dampwood termites, Zootermopsis nevadensis, mimicking natural meetings that occur under bark. During encounters, kings and/or queens were killed and surviving members merged into one colony. After encounters, members of both unrelated colonies cooperated as a single social unit. We determined the colony of origin of replacement reproductives that emerged after death of kings and/or queens. Here, we document that replacement reproductives developed from workers in either or both original colonies, inherited the merged resources of the colony, and sometimes interbred. Because this species shares many characteristics with ancestral termites, these findings demonstrate how ecological factors could have promoted the evolution of eusociality by accelerating and enhancing direct fitness opportunities of helper offspring, rendering relatedness favoring kin selection less critical.     

Sexual isolation of male moths explained by a single pheromone response QTL containing four receptor genes

Long distance sexual communication in moths has fascinated biologists because of the complex, precise female pheromone signals and the extreme sensitivity of males to specific pheromone molecules. Progress has been made in identifying some genes involved in female pheromone production and in male response. However, we have lacked information on the genetic changes involved in evolutionary diversification of these mate-finding mechanisms that is critical to understanding speciation in moths and other taxa. We used a combined quantitative trait locus (QTL) and candidate gene approach to determine the genetic architecture of sexual isolation in males of two congeneric moths, Heliothis subflexa and Heliothis virescens. We report behavioral and neurophysiological evidence that differential male responses to three female-produced chemicals (Z9-14:Ald, Z9-16:Ald, Z11-16:OAc) that maintain sexual isolation of these species are all controlled by a single QTL containing at least four odorant receptor genes. It is not surprising that pheromone receptor differences could control H. subflexa and H. virescens responses to Z9-16:Ald and Z9-14:Ald, respectively. However, central rather than peripheral level control over the positive and negative responses of H. subflexa and H. virescens to Z11-16:OAc had been expected. Tight linkage of these receptor genes indicates that mutations altering male response to complex blends could be maintained in linkage disequilibrium and could affect the speciation process. Other candidate genes such as those coding for pheromone binding proteins did not map to this QTL, but there was some genetic evidence of a QTL for response to Z11-16:OH associated with a sensory neuron membrane protein gene.     

Introgression in hybrid ants is favored in females but selected against in males

Hybridization is not a mere reproductive dead end but has been suggested to play a central role in speciation, for example, by introducing adaptive genetic variation. Our previous study uncovered a unique consequence of hybridization in Formica ants. In a population including two isolated but partially introgressed genetic groups, the females have an apparent hybrid background, whereas the males do not. This situation results in large-scale differences between male and female genomes that are stable throughout generations. Here, we compare genotypes from different developmental stages to investigate how sex-specific introgression and genetic differences between sexes are maintained. We show that strong selection rather than sex-dependent transmission maintains the genetic differences between sexes. All genotype combinations are produced and observed in the eggs of both sexes, but the alleles acquired through hybridization disappear from the haploid males during development from egg to adult as their frequencies drop toward zero. However, the same introgressed alleles increase in frequency and are favored when heterozygous in the females. Genotypes eliminated from males most likely represent incompatibilities arising from hybridization. Our results show an unusual situation of opposite selection, where introgression is favored in diploid females but selected against in haploid males. This finding suggests that introgressed genomic regions harbor both fitness-enhancing and -reducing elements. Our work highlights the complex consequences of hybridization and provides a rare opportunity to observe natural selection in real time in nature.Recent studies suggest hybridization in animals to be more common than previously thought and play a role in both speciation and adaptation (1–3). Toward the end of the speciation process, hybridization commonly leads to inviability and reduced fertility because of incompatible epistatic interactions between genes from different species (4–6). Alternatively, it can result in adaptive introgression of genetic material across the species boundary, where fitness-enhancing gene complexes are transferred from one taxon into another (2, 3).Ants offer unique opportunities to study the process of speciation. Because of sociality and haplodiploidy, some of the consequences of hybridization in ants differ from those in other species. Ants are haplodiploid, as the females (queens and workers) develop through normal sexual reproduction and are diploid, whereas the males develop from unfertilized eggs and are haploid. Therefore, even if a female mates with a male of another species, her haploid sons are not hybrids (7). Furthermore, haploid sons of a hybrid female reveal both recessive and dominant hybrid incompatibilities genome-wide. Haploid male hybrids lack the intact genome of both parental species and thus, face the incompatibility problems seen in F2 hybrids or backcrossed individuals of a diploid species (8, 9). These findings are in accordance with Haldane’s rule, which suggests that the effect of hybrid incompatibilities is strongest in not only the heterogametic but also, the hemizygous (haploid) sex (10). In previously described cases of ant hybridization, the workers are hybrids, but reproductive individuals are produced by mating within a pure line or a species as, for example, in the Pogonomyrmex harvester ants (11) and Solenopsis fire ants (12). Another system (dubbed social hybridogenesis) has been described in Cataglyphis desert ants, where new queens are produced parthenogenetically, whereas workers are hybrids between two genetic lineages (13).Our earlier study based on a population sample of adults revealed yet another exceptional example of hybridization in ants. The population has a history of hybridization between the mound-building wood ants Formica aquilonia and Formica polyctena (9), which has resulted in two genetic groups (R and W) that occupy the same nests and both have diagnostic alleles of their own (Fig. 1). The past history of hybridization has led to introgression of alleles between the groups in such a way that alleles present in one genetic group are also found in the diploid individuals (i.e., females) but not the haploid males of the other genetic group (Fig. 1). In other words, the females (both workers and queens) are apparent hybrids, but the males are not.Open in a separate windowFig. 1.Schematic representation of the male (haploid) and the female (diploid) genomes in the two genetic groups (R and W) of the hybrid ant population. Red rectangles represent genome areas originating from the R group, and blue rectangles represents genome areas originating from the W group. Allele categories are (1) allele diagnostic to W, (2) allele introgressed from W to R, (3) allele introgressed from R to W, and (4) allele diagnostic to R. Introgression is apparent in the females of both groups but not in the males.The parental species of this hybrid population belong to the recently speciated Formica rufa group. At the European scale, F. polyctena is a southern species, whereas F. aquilonia has a boreoalpine distribution occurring in northern and mountainous areas. Their distributions overlap in southern Finland, where our study population is also located. Hybridization may readily take place in their sympatric populations, and the ants are taxonomically difficult to identify (14). Therefore, finding pure parental populations for comparative purposes is difficult. Furthermore, both F. polyctena and F. aquilonia form large supercolonies, a single nest containing many and up to hundreds of queens. The parental species can show large genetic differences within a species even locally because of founder effects and restricted dispersal (15).Introgression into females but not into males is compatible with Haldane’s rule and has resulted in large-scale genetic differences between sexes within the two groups, R and W, of the hybrid population. Mating and sexual reproduction within a group should wipe out such genetic differences within a few generations. The intriguing question thus remains: how are genetic differences between the sexes within the genetic groups created and maintained? Here, we will test two hypotheses that were proposed to explain the situation (9).The selection hypothesis predicts that the genetic differences between male and female genomes result from strong postzygotic selection eliminating incompatible genotype combinations. Strong selection against hybrid males could create large-scale differentiation between sexes, because recessive incompatibilities can be masked in diploid heterozygous females but not haploid males. Consequently, the hybrid males die, but females can survive. The observed genotype frequencies in the adult ants suggest that selection should be very strong and eliminate even most of the offspring genotypes depending on the genetic group and the sex (9).The segregation hypothesis proposes that hybridization has led to the formation of two independently segregating allelic sets, one of which is always transmitted from the mother queens to their sons and the other one is always transmitted to daughters (as if females would be of type XY and males would be of type Y). When the allelic set transmitted to future daughters (X) is fertilized by sperm carrying the paternal complement (Y), the females remain hybrids, and differentiation between sexes is maintained. Two independently segregating allelic sets could be created by chromosomal rearrangements, which can contribute to hybrid incompatibilities and reproductive isolation (16, 17).     

Linked supergenes underlie split sex ratio and social organization in an ant

Sexually reproducing organisms usually invest equally in male and female offspring. Deviations from this pattern have led researchers to new discoveries in the study of parent–offspring conflict, genomic conflict, and cooperative breeding. Some social insect species exhibit the unusual population-level pattern of split sex ratio, wherein some colonies specialize in the production of future queens and others specialize in the production of males. Theoretical work predicted that worker control of sex ratio and variation in relatedness asymmetry among colonies would cause each colony to specialize in the production of one sex. While some empirical tests supported theoretical predictions, others deviated from them, leaving many questions about how split sex ratio emerges. One factor yet to be investigated is whether colony sex ratio may be influenced by the genotypes of queens or workers. Here, we sequence the genomes of 138 Formica glacialis workers from 34 male-producing and 34 gyne-producing colonies to determine whether split sex ratio is under genetic control. We identify a supergene spanning 5.5 Mbp that is closely associated with sex allocation in this system. Strikingly, this supergene is adjacent to another supergene spanning 5 Mbp that is associated with variation in colony queen number. We identify a similar pattern in a second related species, Formica podzolica. The discovery that split sex ratio is determined, at least in part, by a supergene in two species opens future research on the evolutionary drivers of split sex ratio.

The relative investment in male versus female offspring is a vital fitness component of sexually reproducing organisms. Research on sex allocation theory has yielded breakthroughs in our understanding of topics as diverse as parent–offspring conflict, evolution of cooperative breeding, and genomic conflict (1).Among these three topics, parent–offspring conflict is predicted to occur in subdivided populations with strong local mate competition, as seen in polyembryonic parasitoids (2), and in systems with relatedness asymmetry between sisters and brothers, as found in haplodiploid species such as the primitively eusocial wasp Polistes chinensis antennalis (3). Considering the evolution of cooperation, parental control of sex ratio is thought to contribute to the maintenance of cooperative breeding; for example, Seychelles warblers living in high quality territories where helpers provide strong benefits produce an excess of females, the helping sex (4). However, similar patterns of biased sex allocation increasing the frequency of the helping sex are not found among all cooperatively breeding birds (5). The first clear empirical example of intragenomic conflict was based upon the discovery of a chromosome that skews sex ratio from female biased to 100% male in the jewel wasp Nasonia vitripennis (6). This paternal sex ratio chromosome is transmitted through sperm to fertilized eggs, where it causes the loss of other paternally inherited chromosomes to produce exclusively male offspring (7, 8). Subsequent discoveries of sex ratio distorter systems unfolded in different directions, including female-biased sex ratios mediated by endosymbionts (9, 10). These studies opened the door for additional research on intragenomic conflict in multiple contexts, including between sexes (11, 12) and between social insect castes (13).Where there is intragenomic conflict, one resolution is evolution of suppressed recombination to reduce the frequency of deleterious multilocus genotypes. This is illustrated in the standard model of sex chromosome evolution (14, 15), in which selection favors the loss of recombination between a sexually antagonistic locus and a sex-determining locus on the same chromosome, eventually leading to a Y or W chromosome that is exclusively present in one sex. Under the “reduction principle” (16), this is also expected to occur around sex-ratio distorters. In line with this prediction, sex-ratio distorter loci often occur in regions of low recombination (17–20), but we lack evidence for the direction of causality. The reduction principle is also expected to contribute to the formation of autosomal supergenes controlling other complex traits that involve epistatic interactions between two or more loci. Such supergenes have been found to control phenotypes including polymorphic wing coloration in butterflies (21), mating strategies in birds and fungi (22–25), self-incompatibility in plants (26), and colony social organization in ants (27, 28). Autosomal supergenes, like sex chromosomes, are likely to represent the resolution of past intragenomic conflict between two or more loci.Supergenes underlie at least two independently evolved cases of social polymorphism in ants. In the fire ant Solenopsis invicta, colony queen number is controlled by a supergene spanning most of a single chromosome (27). Formica selysi has a similar chromosome-spanning supergene underlying colony queen number, but there is no detectable overlap in gene content between the two (28). More recently, both ant social supergenes were shown to underlie colony queen number in other congeneric species (29, 30). In both systems, the haplotype associated with multiqueen (= polygyne) social structure is a selfish transmission distorter (31–33). These discoveries raise new questions about links between social structure and sex ratio that have been proposed in classic literature about sex allocation in Hymenoptera.Trivers and Hare (34) proposed that queen–worker conflict, which is shaped by relatedness asymmetry within each nest, drives biased sex ratios. Sex ratios represent the proportion of reproductive females and males and do not include workers. Since workers are more related to their full sisters (average relatedness = 0.75) than to their brothers (average relatedness = 0.25), workers in single-queen, monandrous colonies should favor the production of queens over males. Trivers and Hare (34) predicted that worker interests would prevail in these cases since workers provide all care for the brood and that this would result in female-biased offspring production. Queens are equally related to male and female offspring, so they should generally favor a 1:1 sex ratio. In colonies with multiple queens or a single, multiply inseminated queen, the lower relatedness reduces this conflict between queens and workers, resulting in weaker selection for biased sex allocation (1, 34). Although these predictions revolutionized the way that researchers think about how relatedness shapes inclusive fitness in social insect colonies, they are not ubiquitously upheld in empirical studies (1).Strikingly, some social insect species exhibit a nearly complete segregation of male and queen production at the colony level, in a phenomenon known as “split sex ratio.” Such extreme cases have been observed in at least 20 different genera of ants, wasps, and bees (35–37). Boomsma and Grafen (36) argued that this pattern is consistent with worker control of sex ratios in ant populations with variation in relatedness asymmetry: workers that are more related than the population average to their nestmates should favor specializing in the production of new queens (hereafter, “gynes”), while those that are less related than average should specialize in male production (36, 38). The variation in relatedness asymmetry would normally emerge from the number of mates per queen, or from the number of queens per colony, or both.The models of Boomsma and Grafen inspired a burst of empirical research on split sex ratios. Subsequent studies (reviewed in refs. 37, 39, and 40) tested four scenarios that increase the variation in relatedness asymmetry among colonies, including variation in queen number (41–46), variation in queen insemination (41, 42, 45, 47), variation in breeder turnover (46, 48–50), and presence or absence of workers (51), as well as two scenarios not involving relatedness asymmetry, namely resource availability (43, 52–54) and maternally inherited parasites (55, 56). Ants in the genus Formica emerged as a prominent model system, as a result of their widespread and well documented variation in sex ratio and social structure (35). Many species exhibit split sex ratios or highly biased sex ratios (34, 41–44, 47) but not all of these examples follow predicted patterns based on relatedness asymmetry. Finnish populations of Formica truncorum and Formica exsecta follow theoretical predictions: in colonies with a single queen (= monogyne), monandrous queens tend to produce gynes, while polyandrous queens tend to produce males (41, 43). A similar pattern was found in monogyne and polygyne colonies in F. truncorum, with polygyne colonies producing males (44). A socially polymorphic population (i.e., comprised of monogyne and polygyne colonies) of F. selysi and a polygynous population of F. exsecta that exhibit variation in relatedness asymmetry deviated from these predicted patterns (45, 46). Additional studies have identified potential roles of habitat and diet in shaping sex allocation in Formica podzolica (43), F. exsecta (53), and Formica aquilonia (54). Other studies have suggested that investment in sexual offspring is mediated by colony needs for queen replacement (48, 57), with gynes being produced by colonies with relatively few queens. Finally, although Wolbachia is present in some Formica species exhibiting split sex ratio, it does not appear to influence sex ratio in any system studied so far (55, 56).Taken together, it appears that there are yet missing pieces to the puzzle of how and why ants achieve split sex ratios. A meta-analysis attributed about 25% of the observed variance in sex allocation to relatedness asymmetry and variation in queen number (37). Theoretical examinations following from this finding support a possible role for virgin queens (which would produce only male offspring) or queen replacement (58), but another possible factor is that sex allocation by queens is itself under genetic control.Here, we examine the evidence for genetic control, which could be responsible for some of the unexplained variance in patterns of split sex ratio. We 1) conduct a genome-wide association study (GWAS) for variants associated with sex ratio in Formica glacialis, 2) infer transmission patterns of sex-ratio–associated variants from colony-level genotype frequencies, 3) evaluate whether sex ratio and social organization map to the same region of the genome, and 4) examine the sister species F. podzolica (59) to test for a shared genetic basis of sex ratio.     

From the Cover: Highly efficient integration and expression of piggyBac-derived cassettes in the honeybee (Apis mellifera)

Honeybees (Apis mellifera), which are important pollinators of plants, display remarkable individual behaviors that collectively contribute to the organization of a complex society. Advances in dissecting the complex processes of honeybee behavior have been limited in the recent past due to a lack of genetic manipulation tools. These tools are difficult to apply in honeybees because the unit of reproduction is the colony, and many interesting phenotypes are developmentally specified at later stages. Here, we report highly efficient integration and expression of piggyBac-derived cassettes in the honeybee. We demonstrate that 27 and 20% of queens stably transmitted two different expression cassettes to their offspring, which is a 6- to 30-fold increase in efficiency compared with those generally reported in other insect species. This high efficiency implies that an average beekeeping facility with a limited number of colonies can apply this tool. We demonstrated that the cassette stably and efficiently expressed marker genes in progeny under either an artificial or an endogenous promoter. This evidence of efficient expression encourages the use of this system to inhibit gene functions through RNAi in specific tissues and developmental stages by using various promoters. We also showed that the transgenic marker could be used to select transgenic offspring to be employed to facilitate the building of transgenic colonies via the haploid males. We present here the first to our knowledge genetic engineering tool that will efficiently allow for the systematic detection and better understanding of processes underlying the biology of honeybees.The honeybee Apis mellifera is an important pollinator of wildflowers and crop plants with great relevance for the global ecosystem. Substantial losses in colonies have been reported in recent years and have been associated with colony collapse disorder, a scenario in which worker bees abruptly disappear from their colony, and with RNA virus infections transmitted via the ectoparasitic mite Varroa destructor (1–5).Honeybees live in complex societies and display interesting behaviors and developmental processes. The members of a honeybee colony cooperate and produce group phenotypes that allow them to effectively respond to environmental perturbations (6, 7). For instance, honeybees can collectively regulate the temperature of their nest, cooperatively defend against diseases and predators, and exploit food sources efficiently via complex communication systems (8–11).Research on honeybees has contributed to our understanding of social organization, behavior, physiology, development, and genetics. Important discoveries include the communication of food source locations via waggle dances (8, 12, 13), the identification of neural correlates of cognitive faculties (14), the task specialization of colony members on subsets of tasks performed by the colony (7, 12, 15), the complementary sex determination via heterozygosity at a single gene (16, 17), the caste (queen versus worker) differentiation through differential food and the royalactin protein (18), and the releaser function of pheromones emitted by the queen, which affects social behaviors (19).Understanding the interesting features of the honeybee has been limited due to a lack of genetic tools to manipulate gene functions. Conditional expression or inhibition of gene functions using different promoters has allowed for the study of the underlying processes in other organisms. Such expression systems have allowed the systematic dissection of the role of gene functions at later developmental stages, at which point many interesting honeybee phenotypes manifest.Expression cassettes have been introduced into different insect genomes by using transposable elements. The frequencies at which the insects were genetically transformed usually range from below 1 to 5% (20–26). This efficiency would require the screening of at least 100 honeybee colonies to obtain a few transformed queens, making such a system unreasonable. Moreover, the rearing of treated embryos into queens relies on the social environment of a colony, making the development of such procedures difficult.Honeybee colonies typically consist of thousands of worker bees, a single queen, and hundreds of males (drones). The queen produces all of the eggs. The unfertilized eggs, hemizygous at the complementary sex determiner (csd) gene, differentiate into males. The fertilized eggs that have a heterozygous csd genotype (two different sex-determining alleles) develop into females (17), either a queen or worker depending on the various food provided by the worker bees, such as the royal jelly (18, 27). The worker bees process nectar and pollen collected from plants and rear offspring through repeated feeding.In this study, we report the highly efficient integration and expression of piggyBac-derived cassettes, which offer the ability to manipulate gene functions throughout development in an average bee facility.     

A novel modifier gene for plasma von Willebrand factor level maps to distal mouse chromosome 11

Type 1 von Willebrand disease (VWD), characterized by reduced levels of plasma von Willebrand factor (VWF), is the most common inherited bleeding disorder in humans. Penetrance of VWD is incomplete, and expression of the bleeding phenotype is highly variable. In addition, plasma VWF levels vary widely among normal individuals. To identify genes that influence VWF level, we analyzed a genetic cross between RIIIS/J and CASA/Rk, two strains of mice that exhibit a 20-fold difference in plasma VWF level. DNA samples from F₂ progeny demonstrating either extremely high or extremely low plasma VWF levels were pooled and genotyped for 41 markers spanning the autosomal genome. A novel locus accounting for 63% of the total variance in VWF level was mapped to distal mouse chromosome 11, which is distinct from the murine Vwf locus on chromosome 6. We designated this locus Mvwf for “modifier of VWF.” Additional genotyping of as many as 2407 meioses established a high resolution genetic map with gene order Cola1-Itg3a-Ngfr-Mvwf/Gip-Hoxb9-Hoxb1-Cbx·rs2-Cox5a-Gfap. The Mvwf candidate interval between Ngfr and Hoxb9 is ≈0.5 centimorgan (cM). These results demonstrate that a single dominant gene accounts for the low VWF phenotype of RIIIS/J mice in crosses with several other strains. The pattern of inheritance suggests a gain-of-function mutation in a unique component of VWF biosynthesis or processing. Characterization of the human homologue for Mvwf may have relevance for a subset of type 1 VWD cases and may define an important genetic factor modifying penetrance and expression of mutations at the VWF locus.     

New genes emerging for colorectal cancer predisposition

Colorectal cancer(CRC)is one of the most frequent neoplasms and an important cause of mortality in the developed world.This cancer is caused by both genetic and environmental factors although 35%of the variation in CRC susceptibility involves inherited genetic differences.Mendelian syndromes account for about5%of the total burden of CRC,with Lynch syndrome and familial adenomatous polyposis the most common forms.Excluding hereditary forms,there is an important fraction of CRC cases that present familial aggregation for the disease with an unknown germline genetic cause.CRC can be also considered as a complex disease taking into account the common diseasecommom variant hypothesis with a polygenic model of inheritance where the genetic components of common complex diseases correspond mostly to variants of low/moderate effect.So far,30 common,low-penetrance susceptibility variants have been identified for CRC.Recently,new sequencing technologies including exomeand whole-genome sequencing have permitted to add a new approach to facilitate the identification of new genes responsible for human disease predisposition.By using whole-genome sequencing,germline mutations in the POLE and POLD1 genes have been found to be responsible for a new form of CRC genetic predisposition called polymerase proofreading-associated polyposis.     

Radiation and hybridization underpin the spread of the fire ant social supergene

Supergenes are clusters of tightly linked genes that jointly produce complex phenotypes. Although widespread in nature, how such genomic elements are formed and how they spread are in most cases unclear. In the fire ant Solenopsis invicta and closely related species, a “social supergene controls whether a colony maintains one or multiple queens. Here, we show that the three inversions constituting the Social b (Sb) supergene emerged sequentially during the separation of the ancestral lineages of S. invicta and Solenopsis richteri. The two first inversions arose in the ancestral population of both species, while the third one arose in the S. richteri lineage. Once completely assembled in the S. richteri lineage, the supergene first introgressed into S. invicta, and from there into the other species of the socially polymorphic group of South American fire ant species. Surprisingly, the introgression of this large and important genomic element occurred despite recent hybridization being uncommon between several of the species. These results highlight how supergenes can readily move across species boundaries, possibly because of fitness benefits they provide and/or expression of selfish properties favoring their transmission.

Understanding how complex traits requiring multiple novel mutations arise and are maintained in populations is a long-standing question in evolutionary biology (1–3). Supergenes are clusters of multiple, tightly linked genes that collectively produce complex phenotypes (2). They have evolved independently in many taxa and are responsible for intraspecific polymorphism in several important morphological and behavioral traits. The most prominent examples of supergenes are heteromorphic sex chromosomes, which drive the alternate development of males or females. Other examples of supergenes underpinning alternate phenotypes include Batesian mimicry in numerous butterfly species (4–7), self-incompatibility and floral heteromorphy in plants (S locus) (8–11), male meiotic drive (sperm killers) (12), bird plumage color polymorphism (13), and alternative social organization in ant colonies (14–17). In most known cases, the structural integrity of the supergene results from chromosomal rearrangements that suppress local recombination and thereby prevent dissociation of the genetic elements responsible for the integrated expression of complex character suites (5, 10, 13, 16).The first supergene producing alternative social organization was identified in the fire ant Solenopsis invicta (16). In this species, colonies contain either a single egg-laying queen (monogyne social form) or multiple queens (polygyne social form), a fundamental distinction associated with a suite of important individual- and colony-level phenotypic differences (15, 18–21). Studies of invasive populations in the United States have revealed that this supergene comprises two haplotypes, the Social b (Sb) and the Social B (SB), which regulate the polymorphism (16, 22). In S. invicta, monogyne colonies invariably have a single homozygous SB/SB queen and only SB/SB workers, while polygyne colonies always have multiple heterozygous (SB/Sb) queens as well as workers of all three genotypes (15). Moreover, in invasive US populations, the Sb haplotype is responsible for a selfish “green beard” effect whereby SB/Sb (polygyne) workers recognize the cuticular chemical profiles of SB/SB queens and selectively eliminate them as they mature sexually and initiate reproduction (23, 24). Recent studies revealed that social organization also is regulated by the presence/absence of workers with the Sb haplotype in six closely related species of the Solenopsis saevissima species group (i.e., Solenopsis richteri, Solenopsis megergates, Solenopsis macdonaghi, Solenopsis quinquecuspis, the undescribed Solenopsis AdRX, and the undescribed Solenopsis near interrupta) (22, 25, 26). These species collectively are referred to as the socially polymorphic South American fire ants (22).The extant Sb haplotype invariably consists of three inversions that together span a region of ∼11.4 Mb on chromosome 16 containing >476 described genes. As a result, recombination is greatly reduced between the Sb and the SB haplotypes (16, 22, 27). The largest inversion, In(16)1, spans 9.48 Mb of chromosome 16. A second inversion, In(16)2, spans 0.84 Mb between In(16)1 and a third inversion, In(16)3. In(16)2 likely emerged after In(16)1, given that a small fragment of In(16)1—telomeric in SB but central in Sb—is inverted again in the In(16)2 Sb haplotype (22). In(16)3 (1.07 Mb) is located ∼25 kb distant from In(16)2 in a pericentric region of chromosome 16 (22, 28). Previous analyses of the divergence between the Sb and SB haplotypes within species suggested that the three inversions arose over an evolutionarily short time span (22).Reconstructing the evolutionary history of supergene evolution is essential to understanding how such remarkable genomic elements originate and, possibly, the sequence of incorporation of key phenotypic elements into complex traits. The socially polymorphic species are hypothesized to have diverged from the outgroup species S. saevissima and Solenopsis metallica, ∼0.75 to 1.75 million y ago and then radiated within the past ∼500,000 y (22, 29). While a single origin of the Sb haplotype is robustly supported (30, 31), it remains unclear whether this unique element originated in the ancestral population before the radiation, or whether it has invaded the known socially polymorphic species through introgression events (22, 29, 32). Multiple studies have documented recent hybridization involving three of the socially polymorphic Solenopsis species in both the native and introduced ranges (33–37), highlighting a demographic context conducive to such genomic invasion in at least some cases.Here, we present a comprehensive analysis of the history of the fire ant supergene intended to shed light on when and in what order each inversion occurred, and whether introgression of the Sb haplotype between species best explains observed patterns in the comparative genomic data. Using complementary approaches, we conclude that In(16)3 is the oldest inversion and that it likely emerged in the common ancestor of S. richteri and the S. invicta/AdRX lineage. In(16)1 emerged next, during the divergence between the S. richteri and S. invicta/AdRX lineages. Finally, the youngest [In(16)2] inversion emerged in the S. richteri lineage. The supergene comprising all three inversions thus emerged in S. richteri, only to spread to the five most closely related species and confer the social polymorphism to them.     

Social evolution in a new environment: the case of introduced fire ants

The inadvertent introduction of the fire ant Solenopsis invicta to the United States from South America provides the opportunity to study recent social evolution by comparing social organization in native and introduced populations. We report that several important elements of social organization in multiple-queen nests differ consistently and dramatically between ants in Argentina and the United States. Colonies in Argentina contain relatively few queens and they are close relatives, whereas colonies in the United States contain high numbers of unrelated queens. A corollary of these differences is that workers in the native populations are significantly related to the new queens that they rear in contrast to the zero relatedness between workers and new queens in the introduced populations. The observed differences in queen number and relatedness signal a shift in the breeding biology of the introduced ants that is predicted on the basis of the high population densities in the new range. An additional difference in social organization that we observed, greater proportions of permanently unmated queens in introduced than in native populations, is predicted from the loss of alleles at the sex-determining locus and consequent skewing of operational sex ratios in the colonizing ants. Thus, significant recent social evolution in fire ants is consistent with theoretical expectations based on the altered ecology and population genetics of the introduced populations.     

Hipouricemia renal hereditaria tipo 1 y 2 en tres niños españoles. Revisión de casos pediátricos publicados

Hereditary renal hypouricemia is a rare autosomal recessive genetic disorder that involves an isolated defect in uric acid reabsorption at the renal tubules. Patients present with serum uric acid concentrations of less than 2mg/dl (119 micromol/L) with increased fractional excretion above 10%. Most of the patients are asymptomatic and are detected incidentally. However, complications such us nephrolithiasis, hematuria, acute renal failure exercise-induced or after dehydration for acute gastroenteritis, or posterior reversible encephalopaty syndrome (PRES) may develop.Hereditary renal hypouricemia is confirmed by molecular genetic analysis of the two genes which codify the uric acid transport in the kidney tubules. The renal hypouricemia type 1 (OMIM 220150) is characterized by loss-of-function mutations in the SLC22A12 gene which encodes URAT 1 transporter, and the hypouricemia type 2 (OMIM 612076) is caused by defects in the SLC2A9 gene. Homozygous mutations of SLC2A9 cause the most severe forms of the disease.Most mutations have been identified in Japanese adults, and only a few in children.We describe three asyntomatic pediatric Spanish patients with renal hypouricemia, with genetic confirmation, and we make a revision of all of the pediatric cases with genetic study published in the literature.     

Gene set analysis of GWAS data for human longevity highlights the relevance of the insulin/IGF-1 signaling and telomere maintenance pathways

In genome-wide association studies (GWAS) of complex traits, single SNP analysis is still the most applied approach. However, the identified SNPs have small effects and provide limited biological insight. A more appropriate approach to interpret GWAS data of complex traits is to analyze the combined effect of a SNP set grouped per pathway or gene region. We used this approach to study the joint effect on human longevity of genetic variation in two candidate pathways, the insulin/insulin-like growth factor (IGF-1) signaling (IIS) pathway and the telomere maintenance (TM) pathway. For the analyses, we used genotyped GWAS data of 403 unrelated nonagenarians from long-lived sibships collected in the Leiden Longevity Study and 1,670 younger population controls. We analyzed 1,021 SNPs in 68 IIS pathway genes and 88 SNPs in 13 TM pathway genes using four self-contained pathway tests (PLINK set-based test, Global test, GRASS and SNP ratio test). Although we observed small differences between the results of the different pathway tests, they showed consistent significant association of the IIS and TM pathway SNP sets with longevity. Analysis of gene SNP sets from these pathways indicates that the association of the IIS pathway is scattered over several genes (AKT1, AKT3, FOXO4, IGF2, INS, PIK3CA, SGK, SGK2, and YWHAG), while the association of the TM pathway seems to be mainly determined by one gene (POT1). In conclusion, this study shows that genetic variation in genes involved in the IIS and TM pathways is associated with human longevity.     

A novel social polymorphism in a primitively eusocial bee

Halictine sweat bees (Hymenoptera, Halictidae) are model organisms for the evolution of altruism, reproductive castes, and eusocial colony organization. Halictine social behavior is not only extremely variable, but also ecologically and evolutionarily labile. Among social species, colony social organization ranges from communal societies of egalitarian females to eusocial and semisocial ones with reproductive queens and more or less sterile workers. A striking aspect of halictine social variation is the mutual exclusivity of communal and eusocial types of colony social organization within the same species, these two types of social behavior being characteristic of different genera and subgenera. We report a recently discovered exception to this rule in a population of Halictus sexcinctus (Fabricius) at Daimonia-Pyla in southern Greece, that contained both communal and eusocial colonies. Moreover, communal and eusocial females exhibit morphological differences that imply a preimaginal developmental switch, which could also underlie the two types of social behavior. That the communal and eusocial forms are not merely cryptic sister species with different social behavior is indicated by the comparison of mitochondrial DNA sequences of two sections of cytochrome oxidase I, which indicate that Greek specimens of both social types are more similar than they are to conspecifics from elsewhere in Europe. The phylogenetic position of Halictus sexcinctus suggests that this unusual communal/eusocial polymorphism may represent an unstable intermediate step in an evolutionary reversal from eusocial to solitary behavior.     

Inter-chromosomal level of genome organization and longevity-related phenotypes in humans

Studies focusing on unraveling the genetic origin of health span in humans assume that polygenic, aging-related phenotypes are inherited through Mendelian mechanisms of inheritance of individual genes. We use the Framingham Heart Study (FHS) data to examine whether non-Mendelian mechanisms of inheritance can drive linkage of loci on non-homologous chromosomes and whether such mechanisms can be relevant to longevity-related phenotypes. We report on genome-wide inter-chromosomal linkage disequilibrium (LD) and on chromosome-wide intra-chromosomal LD and show that these are real phenomena in the FHS data. Genetic analysis of inheritance in families based on Mendelian segregation reveals that the alleles of single nucleotide polymorphisms (SNPs) in LD at loci on non-homologous chromosomes are inherited as a complex resembling haplotypes of a genetic unit. This result implies that the inter-chromosomal LD is likely caused by non-random assortment of non-homologous chromosomes during meiosis. The risk allele haplotypes can be subject to dominant-negative selection primary through the mechanisms of non-Mendelian inheritance. They can go to extinction within two human generations. The set of SNPs in inter-chromosomal LD (N = 68) is nearly threefold enriched, with high significance (p = 1.6 × 10⁻⁹), on non-synonymous coding variants (N = 28) compared to the entire qualified set of the studied SNPs. Genes for the tightly linked SNPs are involved in fundamental biological processes in an organism. Survival analyses show that the revealed non-genetic linkage is associated with heritable complex phenotype of premature death. Our results suggest the presence of inter-chromosomal level of functional organization in the human genome and highlight a challenging problem of genomics of human health and aging.

Electronic supplementary material

The online version of this article (doi:10.1007/s11357-011-9374-6) contains supplementary material, which is available to authorized users.     

Complexities in the genetic structure of Anopheles gambiae populations in west Africa as revealed by microsatellite DNA analysis

Chromosomal forms of Anopheles gambiae, given the informal designations Bamako, Mopti, and Savannah, have been recognized by the presence or absence of four paracentric inversions on chromosome 2. Studies of karyotype frequencies at sites where the forms occur in sympatry have led to the suggestion that these forms represent species. We conducted a study of the genetic structure of populations of An. gambiae from two villages in Mali, west Africa. Populations at each site were composed of the Bamako and Mopti forms and the sibling species, Anopheles arabiensis. Karyotypes were determined for each individual mosquito and genotypes at 21 microsatellite loci determined. A number of the microsatellites have been physically mapped to polytene chromosomes, making it possible to select loci based on their position relative to the inversions used to define forms. We found that the chromosomal forms differ at all loci on chromosome 2, but there were few differences for loci on other chromosomes. Geographic variation was small. Gene flow appears to vary among different regions within the genome, being lowest on chromosome 2, probably due to hitchhiking with the inversions. We conclude that the majority of observed genetic divergence between chromosomal forms can be explained by forces that need not involve reproductive isolation, although reproductive isolation is not ruled out. We found low levels of gene flow between the sibling species Anopheles gambiae and Anopheles arabiensis, similar to estimates based on observed frequencies of hybrid karyotypes in natural populations.     

Interactions in Colonies of Primitively Social Bees: Artificial Colonies of Lasioglossum zephyrum

Lasioglossum zephyrum usually lives in small colonies but is facultatively solitary. Lone bees and colonies produced from female pupae of the same generation were established in artificial indoor nests. Both the length of the prereproductive period and the number of cells produced per bee per day decreased with increasing colony size. In most colonies, ovarially and behaviorally recognized castes arose, a queen and workers, but with all intergradations. The mean size of queens was larger than that of workers. Nearly all queens mated although few workers did so in rooms with a few males, but mating had no effect on subsequent behavior or ovarian development. In groups of diverse age there was a tendency for the oldest bees to be queens; queens also were larger on the average than workers. In groups of equal age, the largest bee was most often queen. As would be expected for a scarcely social species, mechanisms of social integration (resulting in division of labor and differentiation of castes) mostly appear to involve behavioral features of the solitary ancestors and accidental results of joint occupancy of nests. There is no evidence of direct food or pheromone transfer among adult bees.     

Direct isolation of human BRCA2 gene by transformation-associated recombination in yeast

Mutant forms of the BRCA2 gene contribute significantly to hereditary breast cancer. Isolation of the normal and mutant forms of the BRCA2 gene with its natural promoter would greatly facilitate analysis of the gene and its contribution to breast cancer. We have accomplished the direct isolation of the 90-kb gene from total human DNA by transformation-associated recombination in yeast using a small amount of 5′ and 3′ BRCA2 sequence information. Because the entire isolation procedure of a single chromosomal gene could be accomplished in approximately 2 weeks, the transformation-associated recombination cloning approach is readily applicable to studies of chromosome alterations and human genetic diseases.     

Light-harvesting II (B800-B850 complex) structural genes from Rhodopseudomonas capsulata

The light-harvesting II (LHII) structural genes coding for the (B800-B850 complex) β- and α-polypeptides have been cloned and the nucleotide and deduced polypeptide sequences have been determined. This completes the sequencing of all seven structural genes coding for the structural polypeptides of the photosynthetic apparatus that bind the pigments and cofactors participating in the primary light reactions of photosynthesis. Unlike the structural genes coding for the reaction center L, M, and H subunits and the light-harvesting I (LHI) (B870 complex) structural polypeptides, the LHII structural genes are not within the 46-kilobase photosynthetic gene cluster carried by the R-prime plasmid pRPS404. Identical organization of the β and α structural genes for both LHI and LHII and sequence homologies between the two β-polypeptides and between the two α-polypeptides suggests that both complexes arose by gene duplication from a single ancestral light-harvesting complex and that the putative bacteriochlorophyll binding sequence Ala-X-X-X-His has been absolutely conserved.