Is modularity necessary for evolvability? Remarks on the relationship between pleiotropy and evolvability

Evolvability is the ability to respond to a selective challenge. This requires the capacity to produce the right kind of variation for selection to act upon. To understand evolvability we therefore need to understand the variational properties of biological organisms. Modularity is a variational property, which has been linked to evolvability. If different characters are able to vary independently, selection will be able to optimize each character separately without interference. But although modularity seems like a good design principle for an evolvable organism, it does not therefore follow that it is the only design that can achieve evolvability. In this essay I analyze the effects of modularity and, more generally, pleiotropy on evolvability. Although, pleiotropy causes interference between the adaptation of different characters, it also increases the variational potential of those characters. The most evolvable genetic architectures may often be those with an intermediate level of integration among characters, and in particular those where pleiotropic effects are variable and able to compensate for each other's constraints.     

Are humans increasing bacterial evolvability?

Attempts to control bacterial pathogens have led to an increase in antibiotic-resistant cells and the genetic elements that confer resistance phenotypes. These cells and genes are disseminated simultaneously with the original selective agents via human waste streams. This might lead to a second, unintended consequence of antimicrobial therapy; an increase in the evolvability of all bacterial cells. The genetic variation upon which natural selection acts is a consequence of mutation, recombination and lateral gene transfer (LGT). These processes are under selection, balancing genomic integrity against the advantages accrued by genetic innovation. Saturation of the environment with selective agents might cause directional selection for higher rates of mutation, recombination and LGT, producing unpredictable consequences for humans and the biosphere.     

What are the implications of evolvable molecules?

James Shapiro’s view of evolution is inspired by looking at the molecular mechanisms of mutation. Finding these systems to be intelligent and the mutations non-gradual, Shapiro concludes that neither the role of DNA in development, nor and the role of natural selection in evolution are what we thought them to be. The cases discussed are interesting and may require some modification of theory in biology, but this reviewer finds many of Shapiro’s conclusions unwarranted.     

All stressed out and nowhere to go: does evolvability limit adaptation in invasive species?

Introduced and invasive species are major threats native species and communities and, quite naturally, most scientists and managers think of them in terms of ecological problems. However, species introductions are also experiments in evolution, both for the alien species and for the community that they colonize. We focus here on the introduced species because these offer opportunities to study the properties that allow a species to succeed in a novel habitat and the constraints that limit range expansion. Moreover, an increasing body of evidence from diverse taxa suggests that the introduced species often undergo rapid and observable evolutionary change in their new habitat. Evolution requires genetic variation, which may be decreased or expanded during an invasion, and an evolutionary mechanism such as genetic drift or natural selection. In this volume, we seek to understand how natural selection produces adaptive evolution during invasions. Key questions include what is the role of biotic and abiotic stress in driving adaptation, and what is the source of genetic variation in introduced populations.     

Is metronidazole carcinogenic?

Metronidazole (MTZ, 1-[2-hydroxyethyl]-2-methyl-5-nitroimidazole), an antiparasitic and antibacterial compound, is one of the world’s most used drugs. MTZ is potentially carcinogenic to humans due to the following facts: it is a proven mutagen in bacterial systems, it is genotoxic to human cells and also, it is carcinogenic to animals. However, due to inadequate epidemiological evidence, it is not considered as a risk factor for cancer in humans. As it will be discussed here, the existing population studies are deficient since they have not included sufficient sample size, the follow-up time has not been long enough, and the individual sensitivity to the drug might have been acting as a confounding factor. Due to the increasing use of this drug, more and improved studies are needed to elucidate its mechanism of genotoxicity and its carcinogenic potential.     

Is aging programed?

Development and morphogenesis may easily be thought of as programed, in the sense that they result from a sequence of cellular and molecular events designed by natural selection to produce a given adult phenotype. Aging, except in exceptional cases such as the rapid decay and death of Pacific salmon, is not design but decay. The decay of senescence is not due to natural selection's designing hand, but to its absence. The empirical difference between programed and nonprogramed senescence becomes evident when comparing the stereotypical steps leading to death in salmon contrasted with the lack of such stereotypy in most organisms such as humans and mice. Understanding the distinction between programed development and nonprogramed senescence helps focus attention on the phenotypic performance of adults, which is the focus of natural selection, and therefore be attentive to any unwanted pleiotropic side-effects of genetic or environmental treatments which retard aging.     

Is metronidazole carcinogenic?

Metronidazole (MTZ, 1-[2-hydroxyethyl]-2-methyl-5-nitroimidazole), an antiparasitic and antibacterial compound, is one of the world's most used drugs. MTZ is potentially carcinogenic to humans due to the following facts: it is a proven mutagen in bacterial systems, it is genotoxic to human cells and also, it is carcinogenic to animals. However, due to inadequate epidemiological evidence, it is not considered as a risk factor for cancer in humans. As it will be discussed here, the existing population studies are deficient since they have not included sufficient sample size, the follow-up time has not been long enough, and the individual sensitivity to the drug might have been acting as a confounding factor. Due to the increasing use of this drug, more and improved studies are needed to elucidate its mechanism of genotoxicity and its carcinogenic potential.     

Is sex necessary?

Fungal sexual reproductive modes have markedly high diversity and plasticity, and asexual species have been hypothesized to arise frequently from sexual fungal species. A recent study on the red yeasts provides further support for the notion that sexual ancestors may give rise to shorter-lived asexual species. However, presumed asexual species may also be cryptically sexual, as revealed by other recent studies.See research article: http://www.biomedcentral.com/1471-2148/11/249     

Is London overbedded?

OBJECTIVE--To examine whether there are too many hospital beds in London. DESIGN--Analysis of data from the Hospital In-Patient Enquiry, Mental Health Enquiry, health service indicators, and Emergency Bed Service. SETTING--England, London, and inner London. RESULTS--Hospital admission rates for acute plus geriatric services for London residents were very similar to the national values in all age groups. In the special case considered in the Tomlinson report--acute services in inner London--the admission rate was 22% above the value for England. However, the admission rate of inner deprived Londoners was 9% below that of comparable areas outside London. For psychiatry, admission rates in London roughly equalled those in comparable areas. When special health authorities were excluded, in 1990-1 there were 4% more acute plus geriatric beds available per resident in London than in England. Bed provision has been reduced more rapidly in London than nationally. Extrapolating the trend of bed closures forward indicates that beds (all and acute) per resident in London are now at about the national average. Data from the Emergency Bed Service indicate that the pressure on available hospital beds in London has been increasing since 1985. CONCLUSIONS--Data regarding bed provision and utilisation for all specialties by London residents do not provide a case for reducing the total hospital bed stock in London at a rate faster than elsewhere. Bed closures should take account of London''s relatively poorer social and primary health care circumstances, longer hospital waiting lists, poorer provision of residential homes, and evidence from the Emergency Bed Service of increasing pressure on beds. Higher average costs in London, some unavoidable, are forcing hospital beds to be closed at a faster rate in London than nationally.     

Is tamarisk allelopathic?

Tamarisk (Tamarix ramosissima Ledeb., T. chinensis Lour.), a pernicious invader of riparian areas in the western U.S., is often considered to be allelopathic by virtue of an ability to exude salt from its leaves. However, there is no evidence demonstrating allelopathy or even salinization of soils under tamarisk. We collected soil samples from beneath and just outside of tamarisk canopies at 12 sites along a 110-km reach of Fort Peck Reservoir in northeastern Montana. Samples were analyzed for electrical conductivity (EC), pH and concentration of several nutrients. Plants of western wheatgrass (Agropyron smithii Rydb.), the dominant herbaceous native plant in habitats invaded by tamarisk, were grown in the soil samples as a bioassay. We used principal components analysis (PCA) to explore how intercorrelated soil variables were affected by a tamarisk canopy. EC averaged more than twice as high under a tamarisk canopy than in the open. However, western wheatgrass plants growing in tamarisk-affected soil were 73% larger than those in unaffected soil. PCA analysis indicated that soil beneath a tamarisk canopy had higher values along a gradient of increasing EC and total inorganic N and decreasing pH and NH ₄ ⁺ /NO ₃ ⁻ ratio. This same gradient was also associated with increasing growth of the bioassay. We hypothesize that this fertilization was due to leaf secretions and/or leaf fall, possibly by increased input of nitrogenous organic compounds or increased P solubility. Our study provided no support for an allelopathic effect of tamarisk.     

Is humanity sustainable?

The principles and tenets of management require action to avoid sustained abnormal/pathological conditions. For the sustainability of interactive systems, each system should fall within its normal range of natural variation. This applies to individuals (as for fevers and hypertension, in medicine), populations (e.g. outbreaks of crop pests in agriculture), species (e.g. the rarity of endangerment in conservation) and ecosystems (e.g. abnormally low productivity or diversity in 'ecosystem-based management'). In this paper, we report tests of the hypothesis that the human species is ecologically normal. We reject the hypothesis for almost all of the cases we tested. Our species rarely falls within statistical confidence limits that envelop the central tendencies in variation among other species. For example, our population size, CO(2) production, energy use, biomass consumption and geographical range size differ from those of other species by orders of magnitude. We argue that other measures should be tested in a similar fashion to assess the prevalence of such differences and their practical implications.     

Is it functional?

This report describes the first scientific meeting of the British Society for Proteome Research (BSPR), which was organised jointly with the European Bioinformatics Institute (EBI) and held in July 2004. The focus of the conference was functional proteomics with an emphasis on possible clinical application. The main subjects described here are: the need to simplify samples, the use of biological fluids versus tissue, consideration of biological and experimental variation and the creation of databases to achieve meaningful functional analysis.     

Is bigger better?

To close the gap between research and development, a number of funding organizations focus their efforts on large, translations research projects rather than small research teams and individual scientists. Yet, as Paul van Helden argues, if the support for small, investigator-driven research decreases, there will soon be a dearth of novel discoveries for large research groups to explore.What is medical science all about? Surely it is about the value chain, which begins with basic research and ends—if there is an end—with a useful product. There is a widespread perception that scientists do a lot of basic research, but neglect the application of their findings. To remedy this, a number of organizations and philanthropists have become dedicated advocates of applied or translational research and preferentially fund large consortia rather than small teams or individual scientists. Yet, this is only the latest round in the never-ending debate about how to optimize research. The question remains whether large teams, small groups or individuals are better at making ‘discoveries''.To some extent, a scientific breakthrough depends on the nature of the research. Einstein worked largely alone, and the development of E = mc² is a case in point. He put together insights from many researchers to produce his breakthrough, which has subsequently required teams of scientists to apply. Similarly, drug development may require only an individual or a small team to make the initial discovery. However, it needs many individuals to develop a candidate compound and large teams to conduct clinical trials. On the other hand, Darwin could be seen to have worked the other way around: he had an initial ‘team'' of ‘field assistants''—including the crew of HMS Beagle—but he produced his seminal work essentially alone.Consortium funding is of course attractive for researchers because of the time-scale and the amount of money involved. Clinical trials or large research units may get financial support for 10 years or even longer and in the range of millions of dollars. However, organizations that provide funding on such a large scale require extensive and detailed planning from researchers. The work is subject to frequent reporting and review and often carries a large administrative burden. It has come to the point where this oversight threatens academic freedom. Principal investigators who try to conduct experiments outside the original plan, even if they make sense, lose their funding. Under such conditions, administrative officials are often not there to serve, but to govern.There is a widespread perception that small teams are more productive in terms of published papers. But large-scale science often generates outcomes and product value that a small team cannot. We therefore need both. The problem is the low level of funding for individual scientists and small teams and the resulting cut-throat competition for limited resources. This draws too many researchers to large consortia, which, if successful, can become comfort zones or, if they crash and burn, can cause serious damage.Other factors should also inform our deliberations about the size of research teams and consortia. Which is the better environment in which to train the next generation of scientists? By definition, research should question scientific dogmas and foster innovative thinking. Will a large consortium be able to achieve or even tolerate this?Perhaps these trends can be ascribed to generational differences. Neil Howe described people born between 1943 and 1980 as obsessed with values, individually strong and individualistic, whereas the younger folks born after 1981 place more trust in strong institutions that are seen to be moving society somewhere. If this is true, we can predict that the consortium approach is here to stay, at least for some time. Perhaps the emergence of large-scale science is driven by strong—maybe dictatorial—older individuals and arranged to accommodate the younger generation. If so, it is a win–win situation: we know the value of networking and interacting with others, which comes naturally in the ‘online age''.A down side of large groups is the loss of individual career development. The number of authors per paper has increased constantly. Who does the work and who gets the honour? There is often little recognition for the contribution of most people to publications that arise from large consortia, and it is difficult for peer-reviewers to assess individual contribution. We must take care that we measure what we value and not value what we measure.While it is clear that both large and small groups are essential, good management and balance is required. An alarming trend in my opinion is the inclination to fund new sites for clinical trials, to the detriment of existing facilities. This does not seem to be reasonable or the best use of scarce resources.In the long-term interest of science, we need to consider the correlation of major breakthroughs compared to incremental science with the size of the research group. This is hard to measure, but we must not forget that basic research produces the first leads that are then developed further into products. If the funding for basic science decreases, there will soon be a dearth of topics for ‘big science''.Is there a way out of this dilemma? I would like to suggest that organizations currently funding large consortia allow investigators to set aside a percentage of the money to support basic, curiosity-driven research within these consortia. If they do not rethink their funding strategy, these organizations may find with time that there are few novel discoveries for large groups to explore.     

Is fever beneficial?

Fever, the regulation of body temperature at an elevated level, is a common response to infection throughout the vertebrates, as well as in many species of invertebrate animals. It is probable that fever evolved as an adaptive response to infection hundreds of millions of years ago. Many components of the nonspecific and specific host response to infection are enhanced by small elevations in temperature. Perhaps more important, studies of bacterial- and viral-infected animals have shown that, in general, moderate fevers decrease morbidity and increase survival rate.