The Tarsius gamma-globin gene: pseudogene or active gene?

We sequenced the approximately 5-kb long gamma-globin gene locus from Tarsius bancanus and compared it to the published gamma-globin gene sequence from the related species Tarsius syrichta. The T. syrichta gene's promoter lacks the distal CCAAT box and has a point mutation in the functionally important proximal CCAAT box (CCgAT). This previous finding had suggested that in tarsiers the gamma-globin gene might be a nonexpressed pseudogene. The two tarsier species show the same point mutation at the third nucleotide of the proximal CCAAT element and absence of the distal CCAAT element. Nevertheless, our results indicate that in tarsiers the gamma-globin gene is active, since all three coding regions show only synonymous substitutions and a much lower level of divergence than the noncoding regions. This is significantly different from what would be expected for a silent gene evading stabilizing selection. Thus, we hypothesize that the tarsier's gamma-globin gene locus is expressed even with the mutation in the proximal CCAAT box.     

The evolution of regeneration: adaptive or inherent?

If regeneration were adaptive, it would have arisen autonomously by natural selection from non-regenerative antecedents. Unless each episode coincidentally reinvented the same method of regeneration independently, one would expect the various lineages to differ basically from each other, which they do not. On the other hand, if regeneration were inherent to metazoan life, a derivative of embryogenesis, its various expressions should be as much like each other as they resemble the development of embryonic appendage buds, which they do. It follows that the uneven distribution of regeneration must have been due to its extinction here and there, not as a negative adaptation by natural selection but as a pleiotropic epiphenomenon linked to more useful adaptations with which it was incompatible. In vertebrate evolution, these adaptations have included the transition from aquatic to terrestrial habitats and the modification of poikilothermic to homeothermic metabolism. The former advance rendered the regeneration of weight-bearing limbs impractical; the latter favored rapid wound healing and scar formation which effectively precluded blastema formation. If the latent capacity for regeneration persists in non-regenerative appendages, as would seem to be the case, then the restoration of its overt expression should be possible if the mechanisms of its inhibition could be discovered and eventually rendered ineffectual.     

The antigenic evolution of influenza: drift or thrift?

It is commonly assumed that antibody responses against the influenza virus are polarized in the following manner: strong antibody responses are directed at highly variable antigenic epitopes, which consequently undergo ‘antigenic drift’, while weak antibody responses develop against conserved epitopes. As the highly variable epitopes are in a constant state of flux, current antibody-based vaccine strategies are focused on the conserved epitopes in the expectation that they will provide some level of clinical protection after appropriate boosting. Here, we use a theoretical model to suggest the existence of epitopes of low variability, which elicit a high degree of both clinical and transmission-blocking immunity. We show that several epidemiological features of influenza and its serological and molecular profiles are consistent with this model of ‘antigenic thrift’, and that identifying the protective epitopes of low variability predicted by this model could offer a more viable alternative to regularly update the influenza vaccine than exploiting responses to weakly immunogenic conserved regions.     

The heart-forming fields: one or multiple?

The recent identification of a second mesodermal region as a source of cardiomyocytes has challenged the views on the formation of the heart. This second source of cardiomyocytes is localized centrally on the embryonic disc relative to the remainder of the classic cardiac crescent, a region also called the pharyngeal mesoderm. In this review, we discuss the concept of the primary and secondary cardiogenic fields in the context of folding of the embryo, and the subsequent temporal events involved in formation of the heart. We suggest that, during evolution, the heart developed initially only with the components required for a systemic circulation, namely a sinus venosus, a common atrium, a 'left' ventricle and an arterial cone, the latter being the myocardial outflow tract as seen in the heart of primitive fishes. These components developed in their entirety from the classic cardiac crescent. Only later in the course of evolution did the appearance of novel signalling pathways permit the central part of the cardiac crescent, and possibly the contiguous pharyngeal mesoderm, to develop into the cardiac components required for the pulmonary circulation. These latter components comprise the right ventricle, and that part of the left atrium that derives from the mediastinal myocardium, namely the dorsal atrial wall and the atrial septum. It is these elements which are now recognized as developing from the second field of pharyngeal mesoderm. We suggest that, rather than representing development from separate fields, the cardiac components required for both the systemic and pulmonary circulations are derived by patterning from a single cardiac field, albeit with temporal delay in the process of formation.     

The evolution of early animal embryos: conservation or divergence?

There is a remarkable similarity in the appearance of groups of animal species during periods of their embryonic development. This classic observation has long been viewed as an emphatic realization of the principle of common descent. Despite the importance of embryonic conservation as a unifying concept, models seeking to predict and explain different patterns of conservation have remained in contention. Here, we focus on early embryonic development and discuss several lines of evidence, from recent molecular data, through developmental networks to life-history strategies, that indicate that early animal embryos are not highly conserved. Bringing this evidence together, we argue that the nature of early development often reflects adaptation to diverse ecological niches. Finally, we synthesize old and new ideas to propose a model that accounts for the evolutionary process by which embryos have come to be conserved.     

The origin of RNA interference: Adaptive or neutral evolution?

The origin of RNA interference (RNAi) is usually explained by a defense-based hypothesis, in which RNAi evolved as a defense against transposable elements (TEs) and RNA viruses and was already present in the last eukaryotic common ancestor (LECA). However, since RNA antisense regulation and double-stranded RNAs (dsRNAs) are ancient and widespread phenomena, the origin of defensive RNAi should have occurred in parallel with its regulative functions to avoid imbalances in gene regulation. Thus, we propose a neutral evolutionary hypothesis for the origin of RNAi in which qualitative system drift from a prokaryotic antisense RNA gene regulation mechanism leads to the formation of RNAi through constructive neutral evolution (CNE). We argue that RNAi was already present in the ancestor of LECA before the need for a new defense system arose and that its presence helped to shape eukaryotic genomic architecture and stability.

Where does RNA interference come from? This Essay describes a new step-by-step evolutionary model of how RNA interference might have originated in early eukaryotes through neutral events from the molecular machinery present in prokaryotes.     

The emergence of technology: A cultural step or long-term evolution?

There are two hypotheses to explain the emergence of the technical behaviour: (1) a sudden and fast appearance across the African continent; (2) a long period of emergence and consolidation before it began to spread. We defend this second hypothesis and suggest that the hominid project started around 3 Myr ago, with a ‘biofunctional’ stage. Later than 2.5 Myr, the ‘biomorphotechnical’ stage began (Mode 1), and, at around 1.7 Myr, another stage emerged and developed: the ‘biopotential’ stage (Mode 2). All these stages consist of a two-part process: innovation/emergence, and socialization/generalization of a technical mode.     

Neuropeptide Y receptor gene y6: multiple deaths or resurrections?

The neuropeptide Y family of G-protein-coupled receptors consists of five cloned members in mammals. Four genes give rise to functional receptors in all mammals investigated. The y6 gene is a pseudogene in human and pig and is absent in rat, but generates a functional receptor in rabbit and mouse and probably in the collared peccary (Pecari tajacu), a distant relative of the pig family. We report here that the guinea pig y6 gene has a highly distorted nucleotide sequence with multiple frame-shift mutations. One evolutionary scenario may suggest that y6 was inactivated before the divergence of the mammalian orders and subsequently resurrected in some lineages. However, the pseudogene mutations seem to be distinct in human, pig, and guinea pig, arguing for separate inactivation events. In either case, the y6 gene has a quite unusual evolutionary history with multiple independent deaths or resurrections.     

The gene genie: good fairy or wicked witch?

The so-called genetics revolution rests on a history which at its least can be described as controversial. Modern genetics needs to bear this history in mind. In particular, as with the past, the area of reproductive choice seems particularly vulnerable to potential abuse. Courts in the UK and elsewhere have already shown themselves willing to interfere with the choices of women in the management of their pregnancies. Medical advance, perhaps particularly the capacity to visualise the developing foetus, has added complexity to the question of whether the health care provider has one patient (the woman) or two patients (the woman and the foetus). Additionally, pregnancy is thoroughly monitored in modern medical practice and genetics may provide a further impetus or incentive to mandate increased policing of pregnancy. Gene therapy, once offered, will add further to the desire to ensure that women make the ‘right’ choice, especially when the invasion required is relatively minimal. Further, genetic information is at best predictive, but may, because of its scientific nature, appear to those receiving it to be certain. Thus, the provision of genetic information may reduce rather than enhance choice, unless carefully and sensitively provided. A mature and sophisticated debate about the role of genetics in reproduction is required—engaging rather than bypassing the public—if the real potential of genetics is to be vindicated.     

Adaptation or biased gene conversion? Extending the null hypothesis of molecular evolution

The analysis of evolutionary rates is a popular approach to characterizing the effect of natural selection at the molecular level. Sequences contributing to species adaptation are expected to evolve faster than nonfunctional sequences because favourable mutations have a higher fixation probability than neutral ones. Such an accelerated rate of evolution might be due to factors other than natural selection, in particular GC-biased gene conversion. This is true of neutral sequences, but also of constrained sequences, which can be illustrated using the mouse Fxy gene. Several criteria can discriminate between the natural selection and biased gene conversion models. These criteria suggest that the recently reported human accelerated regions are most likely the result of biased gene conversion. We argue that these regions, far from contributing to human adaptation, might represent the Achilles' heel of our genome.     

The evolution of sexual dimorphism in parasitic cuckoos: sexual selection or coevolution?

Sexual dimorphism is ubiquitous in animals and can result from selection pressure on one or both sexes. Sexual selection has become the predominant explanation for the evolution of sexual dimorphism, with strong selection on size-related mating success in males being the most common situation. The cuckoos (family Cuculidae) provide an exceptional case in which both sexes of many species are freed from the burden of parental care but where coevolution between parasitic cuckoos and their hosts also results in intense selection. Here, we show that size and plumage differences between the sexes in parasitic cuckoos are more likely the result of coevolution than sexual selection. While both sexes changed in size as brood parasitism evolved, we find no evidence for selection on males to become larger. Rather, our analysis indicates stronger selection on parasitic females to become smaller, resulting in a shift from dimorphism with larger females in cuckoos with parental care to dimorphism with larger males in parasitic species. In addition, the evolution of brood parasitism was associated with more cryptic plumage in both sexes, but especially in females, a result that contrasts with the strong plumage dimorphism seen in some other parasitic birds. Examination of the three independent origins of brood parasitism suggests that different parasitic cuckoo lineages followed divergent evolutionary pathways to successful brood parasitism. These results argue for the powerful role of parasite-host coevolution in shaping cuckoo life histories in general and sexual dimorphism in particular.     

The evolution of ADHD: a disorder of communication?

Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed psychiatric condition. Many believe that the central disability is impaired inhibition, which leads to reduced abilities in social skills, self-control, organization and time management. The behaviors identified by clinicians as problematic--inattention, hyperactivity and impulsivity--have been incorporated into several evolutionary models as selectively adaptive cognitive skills for surviving the challenges of a variable Pleistocene environment. We propose that the "disabilities" exhibited by individuals with ADHD are maladaptive, and we concur with Barkley that there is a central impairment in the behavioral inhibition system. The underlying neural anatomy and physiology support the possibility that neurotransmitter pathology may have an impact on other interlinked systems (including language), and may also account for the frequent comorbidity of aggression, anxiety, depression, and learning disabilities (many of which are language-related). Language skills compete with other cognitive activities for the attentional system, and thus the evolution of language could not in fact be independent of the evolution of attention. If language represents the ultimate expression of the attentional system, and some individuals with ADHD are seriously impaired in the coordination of interlinked neural systems (including language), then ADHD fits Jerome Wakefield's definition of "harmful dysfunction," and communication impairments should be investigated more thoroughly by clinicians.     

The evolution of flightlessness: Is history important?

Summary Though most birds and insects are capable of flight (volant) some species are flightless. In this paper I test the hypothesis that phylogenetic constraints have played a role in the evolution of flightlessness. If speciation occurred after the evolutionary transition to flightlessness, inferences concerning the importance of particular aspects of the environment on the probability of the evolution of flightlessness may be statistically spurious because of the inflation of the sample size. Among birds, ratites and penguins illustrate the phenomenon of considerable speciation subsequent to the transition to the evolution of flightlessness. In contrast, the rails represent a group in which each flightless species probably represents a separate evolutionary transition. There are many more flightless insect species than bird species and several orders are monomorphically flightless, the sometimes enormous speciation within the order following and possibly being a consequence of the evolution of flightlessness. While it can be shown in insects that flightlessness has evolved independently many times, there are at least as many cases in which the question cannot be resolved. Therefore, in both birds and insects phylogenetic effects should not be ignored, for the number of evolutionary transitions may be much less than the number of species. The effect of incorporating phylogenetic (or at least taxonomic) constraints into the analysis of habitat factors associated with flightlessness is considered.     

Patterns of gene expression: homology or homocracy?

Numerous papers over the years have stated that the original meaning of the term homology is historical and morphological and denotes organs/structures in two or more species derived from the same structure in their latest common ancestor. However, several more recent papers have extended the use of the term to cover organs/structures which are organised through the expression of homologous genes. This usage has created an ambiguity about the meaning of the term, and we propose to remove this by proposing a new term, homocracy, for organs/structures which are organised through the expression of identical patterning genes. We want to emphasise that the terms homologous and homocratic are not mutually exclusive. Many homologous structures are in all probability homocratic, whereas only a small number of homocratic structures are homologous.     

The evolution of life cycle complexity in aphids: Ecological optimization or historical constraint?

For decades, biologists have debated why many parasites have obligate multihost life cycles. Here, we use comparative phylogenetic analyses of aphids to evaluate the roles of ecological optimization and historical constraint in the evolution of life cycle complexity. If life cycle complexity is adaptive, it should be evolutionarily labile, that is, change in response to selection. We provide evidence that this is true in some aphids (aphidines), but not others (nonaphidines)—groups that differ in the intensity of their relationships with primary hosts. Next, we test specific mechanisms by which life cycle complexity could be adaptive or a constraint. We find that among aphidines there is a strong association between complex life cycles and polyphagy but only a weak correlation between life cycle complexity and reproductive mode. In contrast, among nonaphidines the relationship between life cycle complexity and host breadth is weak but the association between complex life cycles and sexual reproduction is strong. Thus, although the adaptiveness of life cycle complexity appears to be lineage specific, across aphids, life cycle evolution appears to be tightly linked with the evolution of other important natural history traits.     

Organisation of vascular surgical services: evolution or revolution?

The trend towards subspecialisation in hospital services is likely to lead to the development of vascular surgery as a separate specialty. If vascular surgery is to emerge as a high quality service then vascular emergencies--a substantial component of the workload--should be dealt with by surgeons with adequate training, and all patients should have equal access to the service. A specialist vascular surgical unit would have to be large enough to make efficient use of other services that it needs, such as radiology, and so may require the amalgamation of smaller health district units. Because of the differing local degrees of subspecialisation, national or regional strategies for vascular surgery must be developed.