Value of a newly sequenced bacterial genome

Next-generation sequencing(NGS) technologies have made high-throughput sequencing available to medium- and small-size laboratories, culminating in a tidal wave of genomic information. The quantity of sequenced bacterial genomes has not only brought excitement to the field of genomics but also heightened expectations that NGS would boost antibacterial discovery and vaccine development. Although many possible drug and vaccine targets have been discovered, the success rate of genome-based analysis has remained below expectations. Furthermore, NGS has had consequences for genome quality, resulting in an exponential increase in draft(partial data) genome deposits in public databases. If no further interests are expressed for a particular bacterial genome, it is more likely that the sequencing of its genome will be limited to a draft stage, and the painstaking tasks of completing the sequencing of its genome and annotation will not be undertaken. It is important to know what is lost when we settle for a draft genome and to determine the "scientific value" of a newly sequenced genome. This review addresses the expected impact of newly sequenced genomes on antibacterial discovery and vaccinology. Also, it discusses the factors that could be leading to the increase in the number of draft deposits and the consequent loss of relevant biological information.     

The Genetic Basis of Transgressive Ovary Size in Honeybee Workers

Ovarioles are the functional unit of the female insect reproductive organs and the number of ovarioles per ovary strongly influences egg-laying rate and fecundity. Social evolution in the honeybee (Apis mellifera) has resulted in queens with 200–360 total ovarioles and workers with usually 20 or less. In addition, variation in ovariole number among workers relates to worker sensory tuning, foraging behavior, and the ability to lay unfertilized male-destined eggs. To study the genetic architecture of worker ovariole number, we performed a series of crosses between Africanized and European bees that differ in worker ovariole number. Unexpectedly, these crosses produced transgressive worker phenotypes with extreme ovariole numbers that were sensitive to the social environment. We used a new selective pooled DNA interval mapping approach with two Africanized backcrosses to identify quantitative trait loci (QTL) underlying the transgressive ovary phenotype. We identified one QTL on chromosome 11 and found some evidence for another QTL on chromosome 2. Both QTL regions contain plausible functional candidate genes. The ovariole number of foragers was correlated with the sugar concentration of collected nectar, supporting previous studies showing a link between worker physiology and foraging behavior. We discuss how the phenotype of extreme worker ovariole numbers and the underlying genetic factors we identified could be linked to the development of queen traits.THE number of ovariole filaments per ovary is an important female reproductive character that affects fecundity across insect taxa (Richard et al. 2005; Makert et al. 2006). Social insect lineages have evolved a strong dimorphism in ovariole number between reproductive and nonreproductive castes. For example, while most families of bees consistently have 6 total ovarioles, and most species in the family Apidae have 8, the highly social species in the genus Apis (the honeybees) have queens that can have >360 total ovarioles and workers that often have <10 (Winston 1987; Michener 2003). This queen–worker dimorphism is of primary importance because it translates into differential reproductive potential that defines the social roles of these female castes (Winston 1987) and classifies social species in general (Sherman et al. 1995). Furthermore, ovary size (i.e., ovariole number) is the most sensitive indicator of caste-specific development in honeybees (Dedej et al. 1998). The extreme increase in ovariole number for queen honeybees enables high egg-laying rates (>1500 per day) and is apparently a result of selection for increased colony reproduction (growth and fission by swarming) (Seeley 1997). Honeybee queens are thus highly specialized for egg laying, similar to queens of several other social insect taxa, such as army ants or higher termites (Hölldobler and Wilson 1990). Honeybee workers in contrast, do not normally reproduce but perform all other essential activities including foraging for nectar, pollen, and water; caring for brood; and building, maintaining, and defending the colony (Winston 1987; Seeley 1997).While worker honeybees have drastically reduced ovariole numbers relative to queens, they have retained functional ovaries and can produce unfertilized (haploid) male-destined eggs in the absence of queen pheromonal inhibition (Velthuis 1970; Page and Robinson 1994). In the absence of a queen, variation in worker ovariole number translates into differential reproductive success (Makert et al. 2006), but in the presence of a queen this variation is correlated with several other worker attributes. Variation in worker ovariole number may underlie the pollen hoarding syndrome of honeybees, a set of correlated behavioral and physiological traits associated with biases in pollen vs. nectar foraging within honeybee colonies (Amdam et al. 2004, 2006). Ovariole number is thus an important phenotype associated with queen–worker dimorphism but also worker reproduction and division of labor.In honeybees, adult ovariole number is determined during larval development by nutrition. Nurse workers feed queen-destined larvae an overabundance of food while the diet of worker-destined larvae is restricted in the fourth and fifth larval instar (Beetsma 1985). Nurse feeding behavior and thus indirect genetic effects of the colony environment can strongly influence larval developmental trajectory (Beekman et al. 2000; Allsopp et al. 2003; Linksvayer et al. 2009). The differential feeding affects larval gene networks sensitive to nutritional status (the target of rapamycin (TOR) pathway; Patel et al. 2007) to change DNA methylation (Kucharski et al. 2008) and juvenile hormone (JH) titers, with titers higher in queen- than in worker-destined larvae (Hartfelder and Engels 1998). Until the fourth instar, queen- and worker-destined larvae have the same number of ovariole primordia (Reginato and Cruz-Landim 2001). Lower JH titer in workers coincides with disintegration of parts of the cytoskeleton in the germ cells and apoptosis, which decreases ovariole number by the fifth instar (Capella and Hartfelder 1998, 2002). In accord, worker ovarioles can be rescued by JH application during the fourth and early fifth instar (Capella and Hartfelder 1998, 2002).Worker ovariole number and the extent of queen–worker dimorphism for ovariole number vary between species of Apis and between recognized races and strains of Apis mellifera. Both A. cerana and A. mellifera workers typically have <20 total ovarioles (Kapil 1962; Michener and Brothers 1974), but A. cerana queens have only ∼140 ovarioles (Velthuis et al. 1971) while A. mellifera have 200–360 (Michener 1974). In contrast, A. dorsata queens have 248–274 ovarioles and workers have 22–106 (Velthuis et al. 1971). Ruttner and Hesse (1981) studied seven races of A. mellifera and found mean total worker ovariole numbers ranging from 6.4 in A. mellifera mellifera to 18.8 in A. mellifera capensis. Several studies provide evidence that variation in worker ovariole number within populations and between strains has a strong genetic component (Diniz et al. 1993; Thuller et al. 1996, 1998; Jordan et al. 2008).Here, we compared the distribution of worker ovariole number in colonies from a population of feral Africanized bees in Arizona with commercial European bees. Africanized and European bees are derived from lineages separated for ∼1 million years (Whitfield et al. 2006a) and differ in a variety of traits including body size, development time, defensiveness, and behavioral traits associated with the pollen hoarding syndrome (Winston et al. 1983, 1987; Pankiw 2003). Genome scans have identified a number of loci that differ between Africanized and European lineages, and at least some of these genetic differences seem to be the result of divergent selection (Pankiw 2003; Whitfield et al. 2006a; Zayed and Whitfield 2008). In addition, QTL mapping studies for body size and defensive behavior (Hunt et al. 1998, 2007) have suggested few genes with major effect underlying some of these lineage differences.We first describe crosses between Africanized and European bees that revealed segregating variation for extreme ovariole number in workers that were sensitive to the social environment. Next, we describe the results of selective pooled DNA QTL mapping of worker ovariole number in two Africanized backcrosses with transgressive worker ovariole phenotypes, and we list potential candidate genes in the regions of the detected QTL. Finally, we demonstrate that variation in ovariole number, albeit unusual, correlates with differences in worker foraging behavior that have previously been shown to be linked to normal variation in ovariole number.