Many genes are toxic when overexpressed, but general mechanisms for this toxicity have proven elusive. Vavouri et al. (2009) find that intrinsic protein disorder and promiscuous molecular interactions are strong determinants of dosage sensitivity, explaining in part the toxicity of dosage-sensitive oncogenes in mice and humans.
Following a strategy similar to that used in baker’s yeast (Herrgård et al. Nat Biotechnol 26:1155–1160, 2008). A consensus yeast metabolic network obtained from a community approach to systems biology (Herrgård et al. 2008; Dobson et al. BMC Syst Biol 4:145, 2010). Further developments towards a genome-scale metabolic model of yeast (Dobson et al. 2010; Heavner et al. BMC Syst Biol 6:55, 2012). Yeast 5—an expanded reconstruction of the Saccharomyces cerevisiae metabolic network (Heavner et al. 2012) and in Salmonella typhimurium (Thiele et al. BMC Syst Biol 5:8, 2011). A community effort towards a knowledge-base and mathematical model of the human pathogen Salmonellatyphimurium LT2 (Thiele et al. 2011), a recent paper (Thiele et al. Nat Biotechnol 31:419–425, 2013). A community-driven global reconstruction of human metabolism (Thiele et al. 2013) described a much improved ‘community consensus’ reconstruction of the human metabolic network, called Recon 2, and the authors (that include the present ones) have made it freely available via a database at http://humanmetabolism.org/ and in SBML format at Biomodels (http://identifiers.org/biomodels.db/MODEL1109130000). This short analysis summarises the main findings, and suggests some approaches that will be able to exploit the availability of this model to advantage.
Metabolism; Modelling; Systems biology; Networks; Metabolic networks
Motivation: Methods to improve tiling array expression signals are needed to accurately detect genome features. Royce et al. provide statistical normalizations of tile signal based on probe sequence content that promises improved accuracy, and should be independently verified.
Results: Assessment of the sequence content normalization methods identified a problem: confounding of probe sequence content with gene structure (intron/exon) sequence content. Normalization obscured tile signal changes at gene structure boundaries. This and other evidence suggests that simple sequence normalization does not improve detection of genes from tile expression data.
Calcitonin gene-related peptide (CGRP) receptor antagonists are a new treatment principle in acute migraine attacks. Intravenous olcegepant 2.5 mg resulted in 66% headache relief after 2 h, whereas subcutaneous sumatriptan resulted in 81–92% headache relief after 2 h. The intrinsic activity of a parenteral triptan, a 5HT1B/1D receptor agonist, is thus higher than the maximum effect of the parenteral CGRP receptor antagonist olcegepant. For the orally bioavailable CGRP antagonist telcagepant 300 mg, the headache relief was only 55% in one phase III study. These results indicate that CGRP receptor antagonism results in success in the acute treatment of migraine in only a certain fraction of the patients.
In this issue of the JCI, Semple and colleagues report phenotypic evaluation of patients with a germline mutation in the gene encoding serine/threonine kinase AKT2 (see the related article beginning on page 315). Their findings support the idea that the postreceptor actions of insulin in the liver — suppression of gluconeogenesis and stimulation of lipogenesis — are mediated through divergent pathways that can be uncoupled. The results appear to refine the arrangement of crucial steps along these pathways and show how comprehensive study of the phenotype, “deep phenotyping,” of patients who carry rare mutations might complement other types of experiments to elucidate complex pathways and mechanisms.
Perilipin (PLIN1) is a constitutive adipocyte lipid droplet coat protein. N-terminal amphipathic helices and central hydrophobic stretches are thought to anchor it on the lipid droplet, where it appears to function as a scaffold protein regulating lipase activity. We recently identified two different C-terminal PLIN1 frame shift mutations (Leu-404fs and Val-398fs) in patients with a novel subtype of partial lipodystrophy, hypertriglyceridemia, severe insulin resistance, and type 2 diabetes (Gandotra, S., Le Dour, C., Bottomley, W., Cervera, P., Giral, P., Reznik, Y., Charpentier, G., Auclair, M., Delépine, M., Barroso, I., Semple, R. K., Lathrop, M., Lascols, O., Capeau, J., O'Rahilly, S., Magré, J., Savage, D. B., and Vigouroux, C. (2011) N. Engl. J. Med. 364, 740–748.) When overexpressed in preadipocytes, both mutants fail to inhibit basal lipolysis. Here we used bimolecular fluorescence complementation assays to show that the mutants fail to bind ABHD5, permitting its constitutive coactivation of ATGL, resulting in increased basal lipolysis. siRNA-mediated knockdown of either ABHD5 or ATGL expression in the stably transfected cells expressing mutant PLIN1 reduced basal lipolysis. These insights from naturally occurring human variants suggest that the C terminus sequesters ABHD5 and thus inhibits basal ATGL activity. The data also suggest that pharmacological inhibition of ATGL could have therapeutic potential in patients with this rare but metabolically serious disorder.
Cell Biology; Lipase; Lipid Droplets; Lipid Metabolism; Lipodystrophy
Semple et al. (Semple et al. in press, Biol. Lett. (doi:10.1098/rsbl.2009.1062)) argued that the ‘law of brevity’ (an inverse relationship between word length and frequency of use) applies not only to human language but also to vocal signalling in non-human primates, because coding efficiency is paramount in both situations. We analysed the frequency of use of signals of different duration in the vocal repertoires of two Neotropical primate species studied in the wild—the common marmoset (Callithrix jacchus) and the golden-backed uakari (Cacajao melanocephalus). The key prediction of the law of brevity was not supported in either species: although the most frequently emitted calls were relatively brief, they were not the shortest signals in the repertoire. The costs and benefits associated with signals of different duration must be appreciated to understand properly their frequency of use. Although relatively brief vocal signals may be favoured by natural selection in order to minimize energetic costs, the very briefest signals may be ambiguous, contain reduced information or be difficult to detect or locate, and may therefore be selected against. Analogies between human language and vocal communication in animals can be misleading as a basis for understanding frequency of use, because coding efficiency is not the only factor of importance in animal communication, and the costs and benefits associated with different signal durations will vary in a species-specific manner.
law of brevity; Neotropical primates; vocal repertoire; signalling
The ninth column on Evidence-Based Behavioral Medicine is a synthesis of a recent systematic meta-review of multiple health behavior change (MHBC) interventions published by Prochaska and Prochaska in the American Journal of Lifestyle Medicine (Am J Life Med 5:208–221, 2011). Health risk behaviors are highly prevalent and increase the risk of developing and exacerbating chronic disease. The purpose of the meta-review was to examine the efficacy of MHBC interventions in a variety of populations and settings. The available literature was synthesized into three health behavior domains including energy-balance behaviors (physical activity and nutrition), addictive behaviors, and disease-related prevention. Twelve systematic reviews were identified that summarized more than 150 randomized clinical trials. Findings suggest that: (1) Physical activity and nutrition interventions are effective in producing weight loss among adults and female youth, (2) treating two addictive behaviors produces a higher long-term abstinence rate than treating a single behavior, and (3) although preventive interventions for cardiovascular disease and cancer significantly reduce health risk behaviors, reductions in disease incidence are yet to be demonstrated.
Multiple risk; Behavior change; Risk behavior; Lifestyle change; Primary prevention
Müller et al. (Reports, 27 October 2006, p. 654) showed that inhibition of the γ-tubulin ring complex (γ-TuRC) activates the spindle assembly checkpoint (SAC), which led them to suggest that γ-TuRC proteins play molecular roles in SAC activation. Because γ-TuRC inhibition leads to pleiotropic spindle defects, which are well known to activate kinetochore-derived checkpoint signaling, we believe that this conclusion is premature.
Samples of Fermi, Semple, modified Semple, Duck embryo and tissue culture rabies vaccine were inoculated by different routes and in different doses into rabbits, mice and hamsters. The vaccines induced neither detectable interferon nor immediate protection against lethal challenge with CVS rabies virus.
Under similar conditions, high but transient levels of interferon were induced in control animals of the same species with the polynucleotide complex Poly I.C. Hamsters but not mice were protected by Poly I.C.-induced interferon.
No autointerference by vaccine with challenge virus was established. Vaccine-induced protection in mice was directly related to immune response.
The functions of a eukaryotic cell are largely performed by multi-subunit protein complexes that act as molecular machines or information processing modules in cellular networks. An important problem in systems biology is to understand how, in general, these molecular machines respond to perturbations.
In yeast, genes that inhibit growth when their expression is reduced are strongly enriched amongst the subunits of multi-subunit protein complexes. This applies to both the core and peripheral subunits of protein complexes, and the subunits of each complex normally have the same loss-of-function phenotypes. In contrast, genes that inhibit growth when their expression is increased are not enriched amongst the core or peripheral subunits of protein complexes, and the behaviour of one subunit of a complex is not predictive for the other subunits with respect to over-expression phenotypes.
We propose the principle that the overall activity of a protein complex is in general robust to an increase, but not to a decrease in the expression of its subunits. This means that whereas phenotypes resulting from a decrease in gene expression can be predicted because they cluster on networks of protein complexes, over-expression phenotypes cannot be predicted in this way. We discuss the implications of these findings for understanding how cells are regulated, how they evolve, and how genetic perturbations connect to disease in humans.
Dosage compensation is a chromosome-wide regulatory process that balances X-chromosome gene expression between males and females in species whose sex-determining mechanisms require each sex to have a different complement of X chromosomes. Recent advances have clarified the molecular nature of the C. elegans sex-determination signal, which tallies X chromosome number relative to the ploidy and controls both the choice of sexual fate and the process of dosage compensation. Dissecting the sex signal has revealed molecular mechanisms by which small quantitative differences in intracellular signals are translated into dramatically different developmental fates. Recent experiments have also revealed fundamental principles by which C. elegans dosage compensation proteins recognize and bind X chromosomes of XX embryos to reduce gene expression. Dosage compensation proteins function not only in a condensin complex specialized for regulating X-chromosome gene expression, but also in distinct condensin complexes that control other chromosome-wide processes: chromosome segregation and meiotic crossover recombination. The reshuffling of interchangeable molecular parts creates independent machines with similar architecture but distinct biological functions.
The review of ‘The problem surgical colleague’ by Mr John Mosley is both timely and relevant. All surgeons are naturally concerned about the mechanisms in place, both locally and through the General Medical Council (GMC) to deal with fitness-to-practise issues. It is inevitable that criticisms, often unfounded, are voiced by the profession. Most surgeons welcome a fair and transparent system to deal with such matters whilst maintaining the principle of self-regulation. We must accept that there are a small number of surgeons whose practice is impaired to such a degree that they represent a serious patient-safety risk and they must be dealt with appropriately.
As a GMC medical case examiner since 2003, and having dealt with over 600 fitness-to-practise cases, I wish to comment on some of the important issues raised by Mr Mosley, specifically in relation to the surgeon and his or her practice. In doing so, I will set out the investigative process to be followed when fitness-to-practise concerns are brought to the attention of the GMC.
It is argued that by studying some design principles of the immune system, e.g. nonlinearity and being a complex adaptive system, one can easily find some explanations of basic properties of the system e.g. memory and tolerance.
A variety of techniques are used to study the colours of animal signals, including the use of visual matching to colour charts. This paper aims to highlight why they are generally an unsatisfactory tool for the measurement and classification of animal colours and why colour codes based on HTML (really RGB) standards, as advocated in a recent paper, are particularly inappropriate. There are many theoretical arguments against the use of colour charts, not least that human colour vision differs markedly from that of most other animals. However, the focus of this paper is the concern that, even when applied to humans, there is no simple 1:1 mapping from an RGB colour space to the perceived colours in a chart (the results are both printer- and illumination-dependent). We support our criticisms with data from colour matching experiments with humans, involving self-made, printed colour charts.
Colour matching experiments with printed charts involving 11 subjects showed that the choices made by individuals were significantly different between charts that had exactly the same RGB values, but were produced from different printers. Furthermore, individual matches tended to vary under different lighting conditions. Spectrophotometry of the colour charts showed that the reflectance spectra of the charts varied greatly between printers and that equal steps in RGB space were often far from equal in terms of reflectance on the printed charts.
In addition to outlining theoretical criticisms of the use of colour charts, our empirical results show that: individuals vary in their perception of colours, that different printers produce strikingly different results when reproducing what should be the same chart, and that the characteristics of the light irradiating the surface do affect colour perception. Therefore, we urge great caution in the use of colour charts to study animal colour signals. They should be used only as a last resort and in full knowledge of their limitations, with specially produced charts made to high industry standards.
This essay discusses research on incentive-based interventions to promote healthy behavior change, contingency management (CM) and conditional cash transfers (CCT). The overarching point of the essay is that CM and CCT are often treated as distinct areas of inquiry when at their core they represent a common approach. Some potential bi-directional benefits of recognizing this commonality are discussed. Distinct intellectual traditions probably account for the separate paths of CM and CCT to date, with the former being rooted in behavioral psychology and the latter in microeconomics. It is concluded that the emerging field of behavioral economics, which is informed by and integrates principles of each of those disciplines, may provide the proper conceptual framework for integrating CM and CCT.
contingency management; conditional cash transfers; incentive-based interventions
In this Comment, we contrast different conceptions of mind wandering that were presented in two recent theoretical reviews: Smallwood and Schooler (2006) and Watkins (2008). We also introduce a new perspective on the role of executive control in mind wandering by integrating empirical evidence presented in Smallwood and Schooler (2006) with two theoretical frameworks: Watkins’s (2008) elaborated control theory and Klinger’s (1971; 2009) current concerns theory. In contrast to the Smallwood-Schooler claim that mind-wandering recruits executive resources, we argue that mind wandering represents a failure of executive control and that it is dually determined by the presence of automatically generated thoughts in response to environmental and mental cues and the ability of the executive-control system to deal with this interference. We present empirical support for this view from experimental, neuroimaging, and individual-differences research.
Educating a physician workforce that reflects the increasing racial and ethnic diversity of our nation is an ongoing challenge of urgent concern. Many medical school kindergarten through 1 2th grade (K-12) pipeline programs focus on "enriching" underrepresented minority (URM) students using strategies to change or "improve" individual students. This discussion raises concerns over longstanding racial and ethnic inequities in America's public schools that, in part, result in the predictable and systematic underachievement of URM students. These insidious processes can disqualify URM students from successful participation in the medical school pipeline at its earliest stages. The paper also discusses the cultural challenges URM students often face in aspiring to exceptional academic achievement within America's schools. Finally, this paper highlights the need for illustrative examples of medical school-public school partnerships that pursue an agenda of equity to balance the current downstream focus on the enrichment of individual students.
The large number of nonexperimental manuscripts submitted to JABA and the lack of well-defined criteria for evaluating them, has necessitated formulation of a separate editorial policy (see policy statement on page 404 of this issue). The manuscript by Alan E. Kazdin was submitted before the policy concerning nonexperimental manuscripts went into effect and was reviewed by three established researchers who have made substantial methodological contributions to the field (Montrose M. Wolf, Murray Sidman, and L. Keith Miller were Reviewers A, B, and C, respectively). On the basis of the reviewers' comments, it was decided to publish the manuscript with only minor changes. However, because of the fundamental importance of many of the issues discussed in Kazdin's paper and because of the lack of clear agreement on some of these issues, as exemplified in the reviewers' comments, these comments are presented below.
BACKGROUND AND AIMS: General practice in the UK is experiencing difficulty with medical staff recruitment and retention, with reduced numbers choosing careers in general practice or entering principalships, and increases in less-than-full-time working, career breaks, early retirement and locum employment. Information is scarce about the reasons for these changes and factors that could increase recruitment and retention. The UK Medical Careers Research Group (UKMCRG) regularly surveys cohorts of UK medical graduates to determine their career choices and progression. We also invite written comments from respondents about their careers and the factors that influence them. Most respondents report high levels of job satisfaction. A noteworthy minority, however, make critical comments about general practice. Although their views may not represent those of all general practitioners (GPs), they nonetheless indicate a range of concerns that deserve to be understood. This paper reports on respondents' comments about general practice. ANALYSIS OF DOCTORS' COMMENTS: Training Greater exposure to general practice at undergraduate level could help to promote general practice careers and better inform career decisions. Postgraduate general practice training in hospital-based posts was seen as poor quality, irrelevant and run as if it were of secondary importance to service commitments. In contrast, general practice-based postgraduate training was widely praised for good formal teaching that met educational needs. The quality of vocational training was dependent upon the skills and enthusiasm of individual trainers. Recruitment problems Perceived deterrents to choosing general practice were its portrayal, by some hospital-based teachers, as a second class career compared to hospital medicine, and a perception of low morale amongst current GPs. The choice of a career in general practice was commonly made for lifestyle reasons rather than professional aspirations. Some GPs had encountered difficulties in obtaining posts in general practice suited to their needs, while others perceived discrimination. Newly qualified GPs often sought work as non-principals because they felt too inexperienced for partnership or because their domestic situation prevented them from settling in a particular area. Changes to general practice The 1990 National Health Service (NHS) reforms were largely viewed unfavourably, partly because they had led to a substantial increase in GPs' workloads that was compounded by growing public expectations, and partly because the two-tier system of fund-holding was considered unfair. Fund-holding and, more recently, GP commissioning threatened the GP's role as patient advocate by shifting the responsibility for rationing of health care from government to GPs. Some concerns were also expressed about the introduction of primary care groups (PCGs) and trusts (PCTs). Together, increased workload and the continual process of change had, for some, resulted in work-related stress, low morale, reduced job satisfaction and quality of life. These problems had been partially alleviated by the formation of GP co-operatives. Retention difficulties Loss of GPs' time from the NHS workforce occurs in four ways: reduced working hours, temporary career breaks, leaving the NHS to work elsewhere and early retirement. Child rearing and a desire to pursue interests outside medicine were cited as reasons for seeking shorter working hours or career breaks. A desire to reduce pressure of work was a common reason for seeking shorter working hours, taking career breaks, early retirement or leaving NHS general practice. Other reasons for leaving NHS general practice, temporarily or permanently, were difficulty in finding a GP post suited to individual needs and a desire to work abroad. CONCLUSIONS: A cultural change amongst medical educationalists is needed to promote general practice as a career choice that is equally attractive as hospital practice. The introduction of Pre-Registration House Officer (PRHO) placements in general practice and improved flexibility of GP vocational training schemes, together with plans to improve the quality of Senior House Officer (SHO) training in the future, are welcome developments and should address some of the concerns about poor quality GP training raised by our respondents. The reluctance of newly qualified GPs to enter principalships, and the increasing demand from experienced GPs for less-than-full-time work, indicates a need for a greater variety of contractual arrangements to reflect doctors' desires for more flexible patterns of working in general practice.
Embryonic development is defined by the hierarchical dynamical process that translates genetic information (genotype) into a spatial gene expression pattern (phenotype) providing the positional information for the correct unfolding of the organism. The nature and evolutionary implications of genotype–phenotype mapping still remain key topics in evolutionary developmental biology (evo-devo). We have explored here issues of neutrality, robustness, and diversity in evo-devo by means of a simple model of gene regulatory networks. The small size of the system allowed an exhaustive analysis of the entire fitness landscape and the extent of its neutrality. This analysis shows that evolution leads to a class of robust genetic networks with an expression pattern characteristic of lateral inhibition. This class is a repertoire of distinct implementations of this key developmental process, the diversity of which provides valuable clues about its underlying causal principles.
The diversity of life is a consequence of changes in the genotype (genes and their interdependence), but it is upon the observable organism's morphology (phenotype) that natural selection acts. Thus, the study of genotype–phenotype mapping can reveal key mechanisms driving life's capacity of continuous evolution and resilience in diverse environments. In this context, it has been observed that small numbers of genes form robust functional developmental modules, hierarchically reused throughout development. Here we analyze the evolution of small genetic modules toward higher diversity and robustness. Given the small size of the gene network, we can afford to analyze all possible topologies and thus the entire fitness landscape. This exhaustive study as well as simulations of evolutionary processes uncover a set of genetic interactions producing robust and diverse phenotypes. We single out the distinctive features of these networks responsible for their stability against environmental and structural perturbations. More precisely, all these robust genotypes can be related to the key mechanism of lateral inhibition for which a cell of a given type inhibits its neighbors to keep them from adopting the same type. Their distinctive features can thus shed light on the underlying mechanisms leading to pattern formation through lateral inhibition.
A recent article by Rahzani et al. (1) published
in the esteemed Cell Journal reported the antioxidative stress activity of Stachys lavandulifolia
aqueous extract in humans and suggested its consumption as a supplement in the management of
diseases related to oxidative stress. We would like
to emphasize some of the limitations regarding antioxidant supplementation, in general, and Stachys
lavandulifolia, in particular.
It has been established that oxidative stress is involved in the development of a wide variety of chronic and degenerative diseases such as cancer, Parkinson
and Alzheimer’s (2-5). Antioxidants are also effective
in the prevention or reduction of adverse effects related to medication usage (5-10). However, they may
potentially have deleterious effects. A major concern
of antioxidant supplementation is their harmful effect
on reactive oxygen species (ROS) production (prooxidant action), particularly when precise modulation
of ROS levels are necessary for normal cell function
(4-10). In fact, it has been reported that antioxidants
may exhibit pro-oxidant activity under specific conditions. Of particular importance are redox conditions
the dosage and the presence of free transition metals
at cellular sites. For example, the antioxidant vitamin
C in the presence of ferric iron may act as a potent
mediator of lipid peroxidation. It has been suggested
that β-carotene sometimes acts as a pro-oxidant in
the lungs of smokers and similarly vitamin C may increase DNA damage in humans (11, 12). Therefore,
it is necessary to take into account the bioavailability
and differential activities of antioxidant compounds
before their administration.
Other than general considerations for antioxidant
consumption, the aspects of each particular antioxidant should also be considered (3, 13, 14). Recently,
in a preclinical study we reported the renal toxicity
of hydroalcoholic extract of Stachys lavandulifolia
Vahl in Wistar rats (15). In this experimental study we
randomly assigned 100 male Wistar rats to five equal
groups, one control and four experimental. Animals
received intraperitoneal injections of saline or Stachys
lavandulifolia extract (50, 100, 150, 200 mg/kg) for
one month after which blood samples were collected
from half of the animals from each group. Other animals received no injections for one additional month,
then blood samples were obtained. In the groups that
Stachys lavandulifolia Vahl extracts were used for one
month we observed mild degeneration of renal tubular epithelial cells (6, 9). In the second month of the
study these histologic lesions significantly increased
(p< 0.05). We concluded that hydroalcoholic extract
of Stachys lavandulifolia has renal tubular toxicity
which might continue following drug discontinuation
(6, 9, 15).
Therefore, although antioxidant supplements
generally have beneficial effects, as a caution it is
advised to only consume such supplements under
medical supervision in order to avoid any potential
Stachys lavandulifolia; Toxicity; Nephrotoxicity; Antioxidant
A. C. Moss and I. P. Albery (2009) presented a dual-process model of the alcohol-behavior link, integrating alcohol expectancy and alcohol myopia theory. Their integrative theory rests on a number of assumptions including, first, that alcohol expectancies are associations that can be activated automatically by an alcohol-relevant context, and second, that alcohol selectively reduces propositional reasoning. As a result, behavior comes under the control of associative processes after alcohol consumption. We agree with the second but not with the first assumption, based on theoretical and empirical arguments. Although in some cases expectancies may involve a simple association, they are propositional in nature. We demonstrate that this assertion is supported by existing literature cited in Moss and Albery. Moreover, six recent studies consistently demonstrated that under circumstances where executive control is impaired (either as a stable individual difference or under the acute influence of alcohol), associative processes, over and above expectancies, predict alcohol-related behavior. Taken together, the evidence strongly suggests a fundamental distinction between expectancies and associations in memory: effects of propositional expectancies and executive functions are impaired under the acute influence of alcohol but memory associations are not. This difference in perspective not only has theoretical implications, but also leads to different predictions regarding acute alcohol effects in society.
Dual-Process Theories; Automatic and Controlled Processes; Acute Alcohol Effects
The paper of Liu, Gaido and Wolfinger on gene expression during the division cycle of HeLa cells using the data of Whitfield et al. are discussed in order to see whether their analysis is related to gene expression during the division cycle.
The results of Liu, Gaido and Wolfinger demonstrate that different inhibition methods proposed to "synchronize" cells lead to different levels of gene expression. This result, in and of itself, should be taken as evidence that the original work of Whitfield et al. is flawed and should not be used to support the notion that the cells studied were synchronized or that the microarray analyses identify cell-cycle-regulated genes. Furthermore, the DNA content evidence presented by Whitfield et al. supports the proposal that the cells described as 'synchronized' are not synchronized. A comparison of the gene expression amplitudes from two different experiments indicates that the results are not reproducible.
It is concluded that the analysis of Liu, Gaido, and Wolfinger is problematic because their work assumes that the cells they analyze are or were synchronized. The very fact that different inhibition methods lead to different degrees of gene expression should be taken as additional evidence that the experiments should be viewed skeptically rather than accepted as an approach to understanding gene expression during the cell cycle.
Specimens of Starksia were collected throughout the western Atlantic, and a 650-bp portion of the mitochondrial gene cytochrome oxidase-c subunit I (COl) was sequenced as part of a re-analysis of species diversity of western Central Atlantic shorefishes. A neighbor-joining tree constructed from the sequence data suggests the existence of several cryptic species. Voucher specimens from each genetically distinct lineage and color photographs of vouchers taken prior to dissection and preservation were examined for diagnostic morphological characters. The results suggest that Starksia atlantica, Starksia lepicoelia, and Starksia sluiteri are species complexes, and each comprises three or more species. Seven new species are described. DNA data usually support morphological features, but some incongruence between genetic and morphological data exists. Genetic lineages are only recognized as species if supported by morphology. Genetic lineages within western Atlantic Starksia generally correspond to geography, such that members of each species complex have a very restricted geographical distribution. Increasing geographical coverage of sampling locations will almost certainly increase the number of Starksia species and species complexes recognized in the western Atlantic. Combining molecular and morphological investigations is bringing clarity to the taxonomy of many genera of morphologically similar fishes and increasing the number of currently recognized species. Future phylogenetic studies should help resolve species relationships and shed light on patterns of speciation in western Atlantic Starksia.
Starksia; DNA Barcoding; new species; species complex; biogeography