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Evolution of the aminoacyl-tRNA synthetases and the origin of the genetic code.

The aminoacyl-tRNA synthetases exist as two enzyme families which were apparently generated by divergent evolution from two primordial synthetases. The two classes of enzymes exhibit intriguing familial relationships, in that they are distributed nonrandomly within the codon-amino acid matrix of the genetic code. For example, all XCX codons code for amino acids handled by class II synthetases, and all but one of the XUX codons code for amino acids handled by class I synthetases. One interpretation of these patterns is that the synthetases coevolved with the genetic code. The more likely explanation, however, is that the synthetases evolved in the context of an already-established genetic code--a code which developed earlier in an RNA world. The rules which governed the development of the genetic code, and led to certain patterns in the coding catalog between codons and amino acids, would also have governed the subsequent evolution of the synthetases in the context of a fixed code, leading to patterns in synthetase distribution such as those observed. These rules are (1) conservative evolution of amino acid and adapter binding sites and (2) minimization of the disruptive effects on protein structure caused by codon meaning changes.

Amino Acids↗

In vivo molecular evolution reveals biophysical origins of organismal fitness.

In nature, evolution occurs through the continuous adaptation of a population to its environment. At the molecular level, adaptive changes in protein sequence and expression impact organismal fitness and, consequently, dictate population dynamics. Here, we have used a "weak link" method to favor variations in one gene, allowing adaptation to thermostability to be studied in molecular detail as bacteria were grown continuously for approximately 1500 generations. Surprisingly, only six mutant alleles, representing less than 1% of the possible missense mutations, were observed, suggesting a highly constrained molecular landscape during protein evolution. The changes in organismal fitness were linked directly to incremental increases in enzyme stability and activity maxima and corresponded to the narrow temperature ranges where each mutant enjoyed success within the overall population. Thus, continuous evolution of a single gene permits a quantitative approach that extends from the phenotypes of the microbial populations to their underlying biophysical basis.

Adenylate Kinase↗

Comparison of select innate immune mechanisms of fish and mammals.

The study of innate immunity has become increasingly popular since the discovery of homologs of many of the innate immune system components and pathways in lower organisms including invertebrates. As fish occupy a key position in the evolution of the innate and adaptive immune responses, there has been a great deal of interest regarding similarities and differences between their defense mechanisms and those of higher vertebrates. This review focuses on describing select mechanisms of the innate immune responses of fish and the implications for evolution of immunity in higher vertebrates.

Animals↗

Emerging patterns of neuronal responses in supplementary and primary motor areas during sensorimotor adaptation.

Acquisition and retention of sensorimotor skills have been extensively investigated psychophysically, but little is known about the underlying neuronal mechanisms. Here we examine the evolution of neural activity associated with adaptation to new kinematic tasks in two cortical areas: the caudal supplementary motor area (SMA proper), and the primary motor cortex (MI). We investigate the hypothesis that adaptation starts at premotor areas, i.e., higher in the hierarchy of computation, until a stable representation is formed in primary areas. In accordance with previous studies, we found that adaptation can be characterized by two phases: an early phase that is accompanied by fast and substantial reduction of errors, followed by a late phase with slower and more moderate improvements in behavior. We used unsupervised clustering to separate the activity of the single cells into groups of cells with similar response patterns, under the assumption that each such subpopulation forms a functional unit. We specifically observed the number of clusters in each cortical area during early and late phases of the adaptation and found that the number of clusters is higher in the SMA during early phases of adaptation. In contrast, a higher number of clusters was observed in MI only during late phases. Our results suggest a new approach to analyze responses of large populations of neurons and use it to show a hierarchy of dynamic reorganization of functional groups during adaptation.

Adaptation, Physiological↗

Confrontation of morphological and molecular data: the Praomys group (Rodentia, Murinae) as a case of adaptive convergences and morphological stasis.

Phylogenetic relationships in a group of 21 African rodent species designated as the Praomys group (Murinae) were investigated using morphological characters and sequence data from the complete mitochondrial cytochrome b gene and nuclear IRBP gene fragment (840bp). The molecular results confirm the monophyly of the Praomys group, including the species Malacomys verschureni, while the other Malacomys species appear very divergent. The basal relationships within the Praomys group are poorly resolved, suggesting a rapid radiation at about 7-9 million years ago based on genetic divergence rates calibrated from the fossil record. Discrepancies between molecular and morphological results probably reflect of numerous convergences as well as variations in the rates of morphological evolution among lineages. Reconstructions of the ancestral character states suggest a savannah origin for the Praomys group, along with some morphological traits conserved by stasis in savannah taxa. At the same time, forest taxa seem to be characterized by an accelerated morphological evolution, with acquisition of convergent adaptive characters.

Adaptation, Biological↗

A graph model for the evolution of specificity in humoral immunity.

The immune system protects the body against health-threatening entities, known as antigens, through very complex interactions involving the antigens and the system's own entities. One remarkable feature resulting from such interactions is the immune system's ability to improve its capability to fight antigens commonly found in the individual's environment. This adaptation process is called the evolution of specificity. In this paper, we introduce a new mathematical model for the evolution of specificity in humoral immunity, based on Jerne's functional, or idiotypic, network. The evolution of specificity is modeled as the dynamic updating of connection weights in a dynamic graph whose nodes are related to the network's idiotypes. At the core of this weight-updating mechanism are the increase in specificity caused by clonal selection and the decrease in specificity due to the insertion of uncorrelated idiotypes by the bone marrow. As we demonstrate through numerous computer experiments, for appropriate choices of parameters the new model correctly reproduces, in qualitative terms, several immune functions.

Antibody Formation↗

Long-term microclimatic stress causes rapid adaptive radiation of kaiABC clock gene family in a cyanobacterium, Nostoc linckia, from "Evolution Canyons" I and II, Israel.

Cyanobacteria are the only prokaryotes known thus far possessing regulation of physiological functions with approximate daily periodicity, or circadian rhythms, that are controlled by a cluster of three genes, kaiA, kaiB, and kaiC. Here we demonstrate considerably higher genetic polymorphism and extremely rapid evolution of the kaiABC gene family in a filamentous cyanobacterium, Nostoc linckia, permanently exposed to the acute natural environmental stress in the two microsite evolutionary models known as "Evolution Canyons," I (Mount Carmel) and II (Upper Galilee) in Israel. The family consists of five distinct subfamilies (kaiI-kaiV) comprising at least 20 functional genes and pseudogenes. The obtained data suggest that the duplications of kai genes have adaptive significance, and some of them are evolutionarily quite recent (approximately 80,000 years ago). The observed patterns of within- and between-subfamily polymorphisms indicate that positive diversifying, balancing, and purifying selections are the principal driving forces of the kai gene family's evolution.

Bacterial Proteins↗

Hypertensive disorders of pregnancy are an evolutionary adaptation to mitigate the reproductive consequences of the human physique.

The aetiology of hypertensive disorders of pregnancy remains unknown, despite over 30 years of research. The prevalence and natural history of these disorders and the lack of progress in identifying a cause calls for a radical new approach. It is hypothesised that these disorders arise as a consequence of abnormal maternal regulatory mechanisms. The evolution of the physical characteristics unique to humans (bi-pedal gait and a large brain) resulted in a narrow pelvis and a large head. Such a physique is not conducive to viviparity and caused difficult, prolonged and obstructed labour with post-partum haemorrhage--the commonest causes of maternal mortality in the absence of modern medical care. In such circumstances, up to 6.5% of pregnant women will die as a direct consequence of pregnancy, mainly as a result of obstructed labour and haemorrhage. The death toll would have been much higher over millions of years of evolution. These conditions exerted significant adaptive and evolutionary pressure on our species. The adaptations necessary to mitigate the reproductive consequences of the human physique include activation of the coagulation system to reduce post-partum haemorrhage, increased blood pressure to peak after delivery and maintain cerebral perfusion in the face of post-partum blood loss and restriction of fetal growth to prevent obstructed labour. These adaptations must be regulated to guarantee their occurrence but limit their extent to prevent disease. Evidence for blood pressure regulation during pregnancy and a proposed mechanism to achieve this are presented. Regulation requires a redundant feto-placental signal and a single tightly controlled regulator. To guarantee that blood pressure rises, the feto-placental signal is predicted to be conveyed by several different molecules and to be produced in excess in all pregnancies. Normality is then maintained by a single tightly controlled regulator. This model predicts that the feto-placental factors that cause a rise in maternal blood pressure are multiple and produced in disease-causing concentrations in all pregnancies. Disease arises as a consequence of abnormalities in the maternal regulatory mechanism as occurs in say gestational diabetes mellitus. The search for a placental cause for pre-eclampsia is therefore futile. Research should focus on normal pregnancy and the identification of the factor that regulates maternal blood pressure in the second half of pregnancy. This factor will cause hypotension and prevent endothelial activation and have a role analogous to insulin in the regulation of glycaemia and the development of gestational diabetes mellitus.

Acclimatization↗

The evolution of human pathogens: examples and clinical implications.

Recent advances in sequencing of complete bacterial genomes, molecular typing of micro-organisms, and research on microbial pathogenicity factors changed our view on the evolution of human bacterial pathogens. We review current evolutionary concepts on plague and meningococcal disease to illustrate the interplay of molecular phylogeny, epidemiology, and pathogenicity research. Furthermore, examples of the tremendous velocity of bacterial evolution under changing environmental conditions will be discussed.

Adaptation, Physiological↗

Roles of diversifying selection and coordinated evolution in the evolution of amphibian antimicrobial peptides.

Antimicrobial peptides are expressed in the skin of amphibians and are used to prevent infection by microorganisms. Frog species store distinct collections of antimicrobial peptides that show variation in size, charge, conformation, and bactericidal activity, and so the evolution of antimicrobial peptide gene families may reflect the adaptive diversification of these loci. We examined the molecular evolution of antimicrobial peptide transcripts from hylid and ranid frog species. Our results show that after the gene family arose in the common ancestor of the Hylidae and Ranidae, before the divergence of these families in the Mesozoic, it subsequently diversified within these groups with numerous duplication events and divergence of loci. Moreover, we provide evidence that suggests that members of the antimicrobial peptide gene family have been subject to diversifying selection within both propiece and mature domains of hylids and solely within the mature domain of ranids. Finally, our results suggest that coordinated and compensatory amino acid replacements have occurred within the acidic propiece and cationic mature domain of hylid antimicrobial peptide precursors, as has been observed for mammalian defensin genes, but not among those of ranid precursors.

Amino Acid Sequence↗

Telomeres shorten more slowly in long-lived birds and mammals than in short-lived ones.

We know very little about physiological constraints on the evolution of life-history traits in general, and, in particular, about physiological and molecular adjustments that accompany the evolution of variation in lifespan. Identifying mechanisms that underlie adaptive variation in lifespan should provide insight into the evolution of trade-offs between lifespan and other life-history traits. Telomeres, the DNA caps at the ends of linear chromosomes, usually shorten as animals age, but whether telomere rate of change is associated with lifespan is unknown. We measured telomere length in erythrocytes from five bird species with markedly different lifespans. Species with shorter lifespans lost more telomeric repeats with age than species with longer lifespans. A similar correlation is seen in mammals. Furthermore, telomeres did not shorten with age in Leach's storm-petrels, an extremely long-lived bird, but actually lengthened. This novel finding suggests that regulation of telomere length is associated not only with cellular replicative lifespan, but also with organismal lifespan, and that very long-lived organisms have escaped entirely any telomeric constraint on cellular replicative lifespan.

Aging↗

A road map for those who don't know JAK-STAT.

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway transmits information received from extracellular polypeptide signals, through transmembrane receptors, directly to target gene promoters in the nucleus, providing a mechanism for transcriptional regulation without second messengers. Evolutionarily conserved in eukaryotic organisms from slime molds to humans, JAK-STAT signaling appears to be an early adaptation to facilitate intercellular communication that has co-evolved with myriad cellular signaling events. This co-evolution has given rise to highly adapted, ligand-specific signaling pathways that control gene expression. In addition, the JAK-STAT signaling pathways are regulated by a vast array of intrinsic and environmental stimuli, which can add plasticity to the response of a cell or tissue.

Animals↗

Excess non-synonymous substitutions suggest that positive selection episodes occurred during the evolution of DNA-binding domains in the Arabidopsis R2R3-MYB gene family.

It has been suggested that evolutionary changes in regulatory genes may be the predominant molecular mechanism governing both physiological and morphological evolution. R2R3-AtMYB is one of the largest transcription factor gene families in Arabidopsis. Using inferred ancestral sequences we show that several lineages in the R2R3-AtMYB phylogeny experienced excess non-synonymous nucleotide substitution upon gene duplication, indicating episodes of positive selection driving adaptive shifts early in the evolution of this gene family. A noise reduction technique was then used to determine individual sites in DNA-binding domains (R2 domain and R3 domain) of R2R3-AtMYB protein sequence that were favored by frequent non-synonymous substitutions. The analyses reveal that the first helix (helix1) and the second helix (helix2) in both R2 and R3 domains are characterized by more frequent non-synonymous substitutions, and thus experienced significantly higher positive selection pressure than the third helix (helix3) in both domains. Previous MYB protein structure studies have suggested that helix1 and helix2 in both R2 and R3 domains are involved in the characteristic packing of R2R3-AtMYB DNA-binding domains. This suggests that excess non-synonymous substitutions in these helices could have resulted in MYB recognition of novel gene target sites.

Amino Acid Sequence↗

Life, evolution, and the pursuit of single photon sensitivity.

Evolutionary forces have designed a large family of rod and cone photoreceptors, each member of which suits the lifestyle requirements and circadian patterns of a particular species. The three-segment architecture of signal transduction is conspicuous in the biochemistry of photoreceptors and supports their demonstrated properties of extreme sensitivity, low noise levels, extended dynamic range, and light adaptation. The designs elaborated by evolution reflect a gradual process of modification, with the sequential elaboration of layers of control and refinements in control. The end results of this long evolutionary labor are the functional efficiency and dynamic range that give the rod its utility. Our conceptual problems in deriving observed rod properties from the collective features of known rod gene products may well give way when we have learned more about the true composition and topology of the outer segment gene set and both bound and free nucleotide concentrations. The invertebrates have developed alternative solutions to the problems of photoreceptor sensitivity and wide dynamic range. The vertebrate rod represents a truly optimized way to capture and interpret low-intensity photon signals. One may anticipate, with some enthusiasm, those molecular and kinetic data that will permit an understanding of how cones differ from rods and how release from the requirement for single photon detection has shaped the design of this wavelength-specific companion photoreceptor. The utilization by evolution of the three-segment architecture of GTP-dependent signal transduction for other modalities of sensory perception, such as olfaction (Lancet et al., this volume) and gustation (Jones et al., this volume), is certainly a reasonable and successful choice.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-GMP Phosphodiesterases↗

Darwinian evolution does not rule out the gaia hypothesis.

This study explores so-called Darwinian Daisyworlds mathematically rigorously in detail. The original Daisyworld was introduced by Watson & Lovelock (1983) to demonstrate how two species of daisies regulate the global temperature of their planet through competition among these species against the rising solar luminosity, i.e. the Gaia hypothesis. Its variants are Darwinian Daisyworlds in which daisies can adapt themselves to the local temperature. Robertson & Robinson (1998) insist their Darwinian daisies lose the ability for temperature regulation on the basis of their spreadsheet simulations. Lenton & Lovelock (2000) point out that the constraints on adaptation recovers Darwinian daisies' ability of temperature regulation on the basis of their Euler-code simulations. The present study shows there exist the exact and closed-form solutions to these two Daisyworlds. The results contradict the former studies: Robertson and Robinson's daisies do regulate the global temperature even longer than non-adaptive daisies; Lenton and Lovelock's daisies are less adaptive than Robertson and Robinson's daisies because of the constraints on adaptation; the introduction of weak adaptability drives species into a dead end of evolution. Thus, the present results confirm that the Gaia hypothesis and Darwinian evolution can coexist.

Adaptation, Physiological↗