Dissimilar rates in molecular evolution

In this work we present an evolutionary tree based on the differences in the physico-chemical properties involved in amino acid substitutions, instead of considering, for its construction, only the number of changes between species. Phylogenetic trees were constructed from the differences in bulkiness, refractivity index, hydrophobicity, polarity and optical rotation of 9 vertebrate calcitonins. A correlation of the form y = a xb was found between the number of changes (x) and the differences in any given physico-chemical property (y). This correlation implies that the evolutionary time can not be evaluated directly from the number of changes between species.     

Time-dependent rates of molecular evolution

For over half a century, it has been known that the rate of morphological evolution appears to vary with the time frame of measurement. Rates of microevolutionary change, measured between successive generations, were found to be far higher than rates of macroevolutionary change inferred from the fossil record. More recently, it has been suggested that rates of molecular evolution are also time dependent, with the estimated rate depending on the timescale of measurement. This followed surprising observations that estimates of mutation rates, obtained in studies of pedigrees and laboratory mutation-accumulation lines, exceeded long-term substitution rates by an order of magnitude or more. Although a range of studies have provided evidence for such a pattern, the hypothesis remains relatively contentious. Furthermore, there is ongoing discussion about the factors that can cause molecular rate estimates to be dependent on time. Here we present an overview of our current understanding of time-dependent rates. We provide a summary of the evidence for time-dependent rates in animals, bacteria and viruses. We review the various biological and methodological factors that can cause rates to be time dependent, including the effects of natural selection, calibration errors, model misspecification and other artefacts. We also describe the challenges in calibrating estimates of molecular rates, particularly on the intermediate timescales that are critical for an accurate characterization of time-dependent rates. This has important consequences for the use of molecular-clock methods to estimate timescales of recent evolutionary events.     

High rates of molecular evolution in hantaviruses

Hantaviruses are rodent-borne Bunyaviruses that infect the Arvicolinae, Murinae, and Sigmodontinae subfamilies of Muridae. The rate of molecular evolution in the hantaviruses has been previously estimated at approximately 10(-7) nucleotide substitutions per site, per year (substitutions/site/year), based on the assumption of codivergence and hence shared divergence times with their rodent hosts. If substantiated, this would make the hantaviruses among the slowest evolving of all RNA viruses. However, as hantaviruses replicate with an RNA-dependent RNA polymerase, with error rates in the region of one mutation per genome replication, this low rate of nucleotide substitution is anomalous. Here, we use a Bayesian coalescent approach to estimate the rate of nucleotide substitution from serially sampled gene sequence data for hantaviruses known to infect each of the 3 rodent subfamilies: Araraquara virus (Sigmodontinae), Dobrava virus (Murinae), Puumala virus (Arvicolinae), and Tula virus (Arvicolinae). Our results reveal that hantaviruses exhibit short-term substitution rates of 10(-2) to 10(-4) substitutions/site/year and so are within the range exhibited by other RNA viruses. The disparity between this substitution rate and that estimated assuming rodent-hantavirus codivergence suggests that the codivergence hypothesis may need to be reevaluated.     

Darwinian aspects of molecular evolution at sublinear propagation rates

Mean fitness is non-decreasing in the symmetry sector of the frequency trajectory followed in competitive replication at sublinear propagation rates (parabolic time course). This sector contains the pairwise symmetric distribution of species frequencies and its neighboring states, and represents at least half the possible states of an evolving sublinear system. States in the non-symmetry sector produce a negative rate of change in mean fitness. The heterogeneous steady state attained in a finite sublinear system is destabilized by formation of a variant with above-threshold fitness. Evolution in the post-steady-state interval elevates the fitness threshold for coexistence. Contrary to the proposition that ‘parabolic growth invariably results in the survival of all competing species’, only species with sufficient fitness to avoid subthreshold fitness survive. An erratum to this article is available at .     

Positive correlations between molecular and morphological rates of evolution

The existence of positive associations between rates of molecular and morphological evolution (calculated from branch lengths of phylogenetic trees reconstructed using molecular and morphological characters, respectively) is important to issues of neutrality in sequence evolution, phylogenetic reconstructions assuming neutrality, and evolutionary genotype-phenotype mapping. Rates correlate positively when including branches leading to extant species (tips). Excluding tips, trends are similar, but statistical significances decrease systematically. This is due to (a) lower statistical power (excluding tips reduces sample sizes), and (b) rates are solely calculated from inaccurately reconstructed character states of extinct ancestral species, and this noise decreases correlation strengths. Correlations between molecular and morphological rates of evolution increase as more morphological characters are included for phylogenetic reconstruction. Sequence lengths apparently affect correlations along similar principles. Analyses of plant phylogenies confirm those from animals: sampling biases decrease correlations between molecular and morphological rates of evolution. Results confirm that genotype and phenotype are linked, and suggest adaptive components for molecular evolution. The discussion stresses the difficulties associated with analyses and conclusions based on data deduced from phylogenetic reconstruction.     

Variable evolutionary rates in the molecular evolution of mammalian growth hormones

In mammals pituitary growth hormone (GH) shows a slow basal rate of evolution (0.22 ± 0.03 × 10^–9 substitutions/amino acid site/year) which appears to have increased by at least 25–50-fold on two occasions, during the evolution of primates (to at least 10.8 ± 1.3 X 10^–9 substitutions/amino acid site/year) and artiodactyl ruminants (to at least 5.6 ± 1.3 X 10^–9 substitutions/amino acid site/year). That these rate increases are real, and not due to inadvertent comparison of nonorthologous genes, was established by showing that features of the GH gene sequences that are not expressed as mature hormone do not show corresponding changes in evolutionary rate. Thus, analysis of nonsynonymous substitutions in the coding sequence for the mature protein confirmed the rate increases seen in the primate and ruminant GHs, but analysis of nonsynonymous substitutions in the signal peptide sequence, synonymous substitutions in the coding sequence for signal peptide or mature protein, and 5 and 3 untranslated sequences showed no statistically significant changes in evolutionary rate. Evidence that the increases in evolutionary rate are probably due to positive selection is provided by the observation that in the cases of both ruminant and primate GHs the periods of rapid evolution were followed by a return to a slow rate similar to the basal rate seen in other mammalian GHs. Differences between the biological properties of GHs have been identified which may relate to these periods of rapid adaptive molecular evolution. On the basis of sequence data currently available (but excluding rodent GHs which show an intermediate rate, the basis of which is not clear) for most (90%) of evolutionary time mammalian GHs have been in the slow phase of evolution, with possibly most of the few amino acid substitutions that have occurred being neutral in nature. But most (80%) of the amino acid substitutions that have been introduced into GH during the course of mammalian evolution have been accepted during the rapid phases and were adaptive in nature.     

Contrasting rates of mitochondrial molecular evolution in parasitic Diptera and Hymenoptera

We investigated the putative association between the parasitic lifestyle and an accelerated rate of mt genetic divergence, compositional bias, and gene rearrangement, employing a range of parasitic and nonparasitic Diptera and Hymenoptera. Sequences were obtained for the cox1, cox2, 16S, 28S genes, the regions between the cox2 and atp8 genes, and between the nad3 and nad5 genes. Relative rate tests indicated generally that the parasitic lifestyle was not associated with an increased rate of genetic divergence in the Diptera but reaffirmed that it was in the Hymenoptera. Similarly, a departure from compositional stationarity was not associated with parasitic Diptera but was in parasitic Hymenoptera. Finally, mitochondrial (mt) gene rearrangements were not observed in any of the dipteran species examined. The results indicate that these genetic phenomena are not accelerated in parasitic Diptera compared with nonparasitic Diptera. A possible explanation for the differences in the rate of mt molecular evolution in parasitic Diptera and Hymenoptera is the extraordinary level of radiation that has occurred within the parasitic Hymenoptera but not in any of the dipteran parasitic lineages. If speciation events in the parasitic Hymenoptera are associated with founder events, a faster rate of molecular evolution is expected. Alternatively, biological differences between endoparasitic Hymenoptera and endoparasitic Diptera may also account for the differences observed in molecular evolution.     

The structure of cytochromec and the rates of molecular evolution

Summary The x-ray structure analysis of ferricytochromec shows the reasons for the evolutionary conservatism of hydrophobic and aromatic side chains, lysines, and glycines, which had been observed from comparisons of amino acid sequences from over 30 species. It also shows that the negative character of one portion of the molecular surface is conserved, even though individual acidic side chains are not, and that positive charges are localized around two hydrophobic channels leading from the interior to the surface.The reason for the unusual evolutionary conservation of surface features in cytochromesc is probably the interaction of the molecule with two other large macromolecular complexes, its reductase and oxidase. This conservation of surface structure also explains the relatively slow rate of change of cytochromec sequences in comparison with the globins and enzymes of similar size.The rate of evolution of a protein is the rate of occurrence of mutations in the genome modified by the probability that a random change in amino acid sequence will be tolerable in a functioning protein. The observed rates of change in fibrinopeptides, the globins, cytochromec, and several enzymes are interpreted in terms of the proteins' biological roles.Contribution No. 4114 from the Norman W. Church Laboratory of Chemical Biology, California Institute of Technology, Pasadena, California 91109.     

Chromosomal rearrangements are associated with higher rates of molecular evolution in mammals

Evolutionary rates are not uniformly distributed across the genome. Knowledge about the biological causes of this observation is still incomplete, but its exploration has provided valuable insight into the genomical, historical and demographical variables that influence rates of genetic divergence. Recent studies suggest a possible association between chromosomal rearrangements and regions of greater divergence, but evidence is limited and contradictory. Here, we test the hypothesis of a relationship between chromosomal rearrangements and higher rates of molecular evolution by studying the genomic distribution of divergence between 12,000 human-mouse orthologous genes. Our results clearly show that genes located in genomic regions that have been highly rearranged between the two species present higher rates of synonymous (0.7686 vs. 0.7076) and non-synonymous substitution (0.1014 vs. 0.0871), and that synonymous substitution rates are higher in genes close to the breakpoints of individual rearrangements. The many potential causes of such striking are discussed, particularly in the light of speciation models suggesting that chromosomal rearrangements may have contributed to some of the speciation processes along the human and mouse lineages. Still, there are other possible causes and further research is needed to properly explore them.     

Fast molecular evolution associated with high active metabolic rates in poison frogs

Molecular evolution is simultaneously paced by mutation rate, genetic drift, and natural selection. Life history traits also affect the speed of accumulation of nucleotide changes. For instance, small body size, rapid generation time, production of reactive oxygen species (ROS), and high resting metabolic rate (RMR) are suggested to be associated with faster rates of molecular evolution. However, phylogenetic correlation analyses failed to support a relationship between RMR and molecular evolution in ectotherms. In addition, RMR might underestimate the metabolic budget (e.g., digestion, reproduction, or escaping predation). An alternative is to test other metabolic rates, such as active metabolic rate (AMR), and their association with molecular evolution. Here, I present comparative analyses of the associations between life history traits (i.e., AMR, RMR, body mass, and fecundity) with rates of molecular evolution of and mitochondrial loci from a large ectotherm clade, the poison frogs (Dendrobatidae). My results support a strong positive association between mass-specific AMR and rates of molecular evolution for both mitochondrial and nuclear loci. In addition, I found weaker and genome-specific covariates such as body mass and fecundity for mitochondrial and nuclear loci, respectively. No direct association was found between mass-specific RMR and rates of molecular evolution. Thus, I provide a mechanistic hypothesis of the link between AMRs and the rate of molecular evolution based on an increase in ROS within germ line cells during periodic bouts of hypoxia/hyperoxia related to aerobic exercise. Finally, I propose a multifactorial model that includes AMR as a predictor of the rate of molecular evolution in ectothermic lineages.     

The effects of kin selection on rates of molecular evolution in social insects

The evolution of sociality represented a major transition point in biological history. The most advanced societies, such as those displayed by social insects, consist of reproductive and nonreproductive castes. The caste system fundamentally affects the way natural selection operates. Specifically, selection acts directly on reproductive castes, such as queens, but only indirectly through the process of kin selection on nonreproductive castes, such as workers. In this study, we present theoretical analyses to determine the rate of substitution at loci expressed exclusively in the queen or worker castes. We show that the rate of substitution is the same for queen- and worker-selected loci when the queen is singly mated. In contrast, when a queen is multiply mated, queen-selected loci show higher rates of substitution for adaptive alleles and lower rates of substitution for deleterious alleles than worker-selected loci. We compare our theoretical expectations to previously obtained genomic data from the honeybee, Apis mellifera, where queens mate multiply and the fire ant, Solenopsis invicta, where queens mate singly and find that rates of evolution of queen- and worker-selected loci are consistent with our predictions. Overall, our research tests theoretical expectations using empirically obtained genomic data to better understand the evolution of advanced societies.     

Sequence diversity and rates of molecular evolution between sheep and cattle genes

Experiments that aim to identify genes of importance in sheep are currently inhibited by a paucity of genomic resources. One approach, therefore, is to exploit the wealth of data and associated capabilities becoming available for the bovine genome. Cross-species application of microarrays and comparative sequencing to identify single nucleotide polymorphisms are two possibilities; however, both are dependant on the level of nucleotide sequence similarity between the two species. This study used 120 gene orthologues consisting of over 60 kb of aligned sequence to estimate the gene diversity between cattle and sheep. Less than 3% of protein-coding nucleotide positions were found to be different, indicating that the prospect for successfully using cross-species strategies is high. Substitution at synonymous sites ranged between 6.9 and 7.7% (+/- 0.3%), and was higher than at non-synonymous sites (1.4-1.7 +/- 0.1%). The relative rate test was used to determine whether the observed mutation rates were constant between the two lineages. While the rate at synonymous sites appeared constant, the rate at non-synonymous sites was significantly higher within the caprinae lineage (sheep) when compared with bovinae (cattle; chi2 = 10.03; d.f. = 1, P < 0.01). This is the first demonstration that variable rates of molecular evolution may be present within the family Bovidae.     

Inferring clocks when lacking rocks: the variable rates of molecular evolution in bacteria

Background  

Because bacteria do not have a robust fossil record, attempts to infer the timing of events in their evolutionary history requires comparisons of molecular sequences. This use of molecular clocks is based on the assumptions that substitution rates for homologous genes or sites are fairly constant through time and across taxa. Violation of these conditions can lead to erroneous inferences and result in estimates that are off by orders of magnitude. In this study, we examine the consistency of substitution rates among a set of conserved genes in diverse bacterial lineages, and address the questions regarding the validity of molecular dating.     

Erratic rates of molecular evolution and incongruence of fossil and molecular divergence time estimates in Ostracoda (Crustacea)

Dating evolutionary origins of taxa is essential for understanding rates and timing of evolutionary events, often inciting intense debate when molecular estimates differ from first fossil appearances. For numerous reasons, ostracods present a challenging case study of rates of evolution and congruence of fossil and molecular divergence time estimates. On the one hand, ostracods have one of the densest fossil records of any metazoan group. However, taxonomy of fossil ostracods is controversial, owing at least in part to homoplasy of carapaces, the most commonly fossilized part. In addition, rates of evolution are variable in ostracods. Here, we report evidence of extreme variation in the rate of molecular evolution in different ostracod groups. This rate is significantly elevated in Halocyprid ostracods, a widespread planktonic group, consistent with previous observations that planktonic groups show elevated rates of molecular evolution. At the same time, the rate of molecular evolution is slow in the lineage leading to Manawa staceyi, a relict species that we estimate diverged approximately 500 million years ago from its closest known living relative. We also report multiple cases of significant incongruence between fossil and molecular estimates of divergence times in Ostracoda. Although relaxed clock methods improve the congruence of fossil and molecular divergence estimates over strict clock models, incongruence is present regardless of method. We hypothesize that this observed incongruence is driven largely by problems with taxonomy of fossil Ostracoda. Our results illustrate the difficulty in consistently estimating lineage divergence times, even in the presence of a voluminous fossil record.     

Testing the link between the latitudinal gradient in species richness and rates of molecular evolution

Numerous hypotheses have been proposed to explain latitudinal gradients in species richness, but all are subject to ongoing debate. Here we examine Rohde's (1978, 1992) hypothesis, which proposes that climatic conditions at low latitudes lead to elevated rates of speciation. This hypothesis predicts that rates of molecular evolution should increase towards lower latitudes, but this prediction has never been tested. We discuss potential links between rates of molecular evolution and latitudinal diversity gradients, and present the first test of latitudinal variation in rates of molecular evolution. Using 45 phylogenetically independent, latitudinally separated pairs of bird species and higher taxa, we compare rates of evolution of two mitochondrial genes and DNA-DNA hybridization distances. We find no support for an effect of latitude on rate of molecular evolution. This result casts doubt on the generality of a key component of Rohde's hypothesis linking climate and speciation.     

A mitogenomic timescale for birds detects variable phylogenetic rates of molecular evolution and refutes the standard molecular clock

Current understanding of the diversification of birds is hindered by their incomplete fossil record and uncertainty in phylogenetic relationships and phylogenetic rates of molecular evolution. Here we performed the first comprehensive analysis of mitogenomic data of 48 vertebrates, including 35 birds, to derive a Bayesian timescale for avian evolution and to estimate rates of DNA evolution. Our approach used multiple fossil time constraints scattered throughout the phylogenetic tree and accounts for uncertainties in time constraints, branch lengths, and heterogeneity of rates of DNA evolution. We estimated that the major vertebrate lineages originated in the Permian; the 95% credible intervals of our estimated ages of the origin of archosaurs (258 MYA), the amniote-amphibian split (356 MYA), and the archosaur-lizard divergence (278 MYA) bracket estimates from the fossil record. The origin of modern orders of birds was estimated to have occurred throughout the Cretaceous beginning about 139 MYA, arguing against a cataclysmic extinction of lineages at the Cretaceous/Tertiary boundary. We identified fossils that are useful as time constraints within vertebrates. Our timescale reveals that rates of molecular evolution vary across genes and among taxa through time, thereby refuting the widely used mitogenomic or cytochrome b molecular clock in birds. Moreover, the 5-Myr divergence time assumed between 2 genera of geese (Branta and Anser) to originally calibrate the standard mitochondrial clock rate of 0.01 substitutions per site per lineage per Myr (s/s/l/Myr) in birds was shown to be underestimated by about 9.5 Myr. Phylogenetic rates in birds vary between 0.0009 and 0.012 s/s/l/Myr, indicating that many phylogenetic splits among avian taxa also have been underestimated and need to be revised. We found no support for the hypothesis that the molecular clock in birds "ticks" according to a constant rate of substitution per unit of mass-specific metabolic energy rather than per unit of time, as recently suggested. Our analysis advances knowledge of rates of DNA evolution across birds and other vertebrates and will, therefore, aid comparative biology studies that seek to infer the origin and timing of major adaptive shifts in vertebrates.     

r8s: inferring absolute rates of molecular evolution and divergence times in the absence of a molecular clock

SUMMARY: Estimating divergence times and rates of substitution from sequence data is plagued by the problem of rate variation between lineages. R8s version 1.5 is a program which uses parametric, nonparametric and semiparametric methods to relax the assumption of constant rates of evolution to obtain better estimates of rates and times. Unlike most programs for rate inference or phylogenetics, r8s permits users to convert results to absolute rates and ages by constraining one or more node times to be fixed, minimum or maximum ages (using fossil or other evidence). Version 1.5 uses truncated Newton nonlinear optimization code with bound constraints, offering superior performance over previous versions. AVAILABILITY: The linux executable, C source code, sample data sets and user manual are available free at http://ginger.ucdavis.edu/r8s.     

The molecular evolution of pituitary growth hormone prolactin and placental lactogen: A protein family showing variable rates of evolution

Summary Pituitary growth hormone and prolactin, together with the homologous placental hormones, comprise a family of related protein hormones. Complete or partial amino acid sequences of seven mammalian growth hormones, six mammalian prolactins and one placental lactogen are available, and have been compared. A phylogenetic tree has been constructed which describes the relationships within the family. At least two gene duplications have occurred during the evolution of these proteins. Rates of evolution in the family have been quite variable, the overall rate of evolution having been apparently fairly slow, but having increased markedly on several occasions, most notably in the evolution of human (and, on the basis of immunological relationships, probably other primate) growth hormones and rat (and possibly other rodent) prolactins.