Overdispersion of the molecular clock varies between yeast, Drosophila and mammals

Although protein evolution can be approximated as a "molecular evolutionary clock," it is well known that sequence change departs from a clock-like Poisson expectation. Through studying the deviations from a molecular clock, insight can be gained into the forces shaping evolution at the level of proteins. Generally, substitution patterns that show greater variance than the Poisson expectation are said to be "overdispersed." Overdispersion of sequence change may result from temporal variation in the rate at which amino acid substitutions occur on a phylogeny. By comparing the genomes of four species of yeast, five species of Drosophila, and five species of mammals, we show that the extent of overdispersion shows a strong negative correlation with the effective population size of these organisms. Yeast proteins show very little overdispersion, while mammalian proteins show substantial overdispersion. Additionally, X-linked genes, which have reduced effective population size, have gene products that show increased overdispersion in both Drosophila and mammals. Our research suggests that mutational robustness is more pervasive in organisms with large population sizes and that robustness acts to stabilize the molecular evolutionary clock of sequence change.     

Partitioning the variation in mammalian substitution rates

We have used analysis of variance to partition the variation in synonymous and amino acid substitution rates between three effects (gene, lineage, and a gene-by-lineage interaction) in mammalian nuclear and mitochondrial genes. We find that gene effects are stronger for amino acid substitution rates than for synonymous substitution rates and that lineage effects are stronger for synonymous substitution rates than for amino acid substitution rates. Gene-by-lineage interactions, equivalent to overdispersion corrected for lineage effects, are found in amino acid substitutions but not in synonymous substitutions. The variance in the ratio of amino acid and synonymous substitution rates is dominated by gene effects, but there is also a significant gene-by-lineage interaction.     

Site-to-site variation of synonymous substitution rates

We develop a new model for studying the molecular evolution of protein-coding DNA sequences. In contrast to existing models, we incorporate the potential for site-to-site heterogeneity of both synonymous and nonsynonymous substitution rates. We demonstrate that within-gene heterogeneity of synonymous substitution rates appears to be common. Using the new family of models, we investigate the utility of a variety of new statistical inference procedures, and we pay particular attention to issues surrounding the detection of sites undergoing positive selection. We discuss how failure to model synonymous rate variation in the model can lead to misidentification of sites as positively selected.     

Synonymous substitution rates in Drosophila: Mitochondrial versus nuclear genes

Synonymous substitution rates in mitochondrial and nuclear genes of Drosophila were compared. To make accurate comparisons, we considered the following: (1) relative synonymous rates, which do not require divergence time estimates, should be used; (2) methods estimating divergence should take into account base composition; (3) only very closely related species should be used to avoid effects of saturation; (4) the heterogeneity of rates should be examined. We modified the methods estimating synonymous substitution numbers to account for base composition bias. By using these methods, we found that mitochondrial genes have 1.7–3.4 times higher synonymous substitution rates than the fastest nuclear genes or 4.5–9.0 times higher rates than the average nuclear genes. The average rate of synonymous transversions was 2.7 (estimated from the melanogaster species subgroup) or 2.9 (estimated from the obscura group) times higher in mitochondrial genes than in nuclear genes. Synonymous transversions in mitochondrial genes occurred at an approximately equivalent rate to those in the fastest nuclear genes. This last result is not consistent with the hypothesis that the difference in turnover rates between mitochondrial and nuclear genomes is the major factor determining higher synonymous substitution rates in mtDNA. We conclude that the difference in synonymous substitution rates is due to a combination of two factors: a higher transitional mutation rate in mtDNA and constraints on nuclear genes due to selection for codon usage. Received: 27 November 1996 / Accepted: 8 May 1997     

Rate variation during molecular evolution: creationism and the cytochrome c molecular clock

Molecular clocks based upon amino acid sequences in proteins have played a major role in the clarification of evolutionary phylogenies. Creationist criticisms of these methods sometimes rely upon data that might initially seem to be paradoxical. For example, human cytochrome c differs from that of an alligator by 13 amino acids but differs by 14 amino acids from a much more closely related primate, Otolemur garnettii. The apparent anomaly is resolved by taking into consideration the variable substitution rate of cytochrome c, particularly among primates. This paper traces some of the history of extensive research into the topic of rate heterogeneity in cytochrome c including data from cytochrome c pseudogenes.     

Human-macaque comparisons illuminate variation in neutral substitution rates

Background  

The evolutionary distance between human and macaque is particularly attractive for investigating local variation in neutral substitution rates, because substitutions can be inferred more reliably than in comparisons with rodents and are less influenced by the effects of current and ancient diversity than in comparisons with closer primates. Here we investigate the human-macaque neutral substitution rate as a function of a number of genomic parameters.     

A survey of nuclear ribosomal internal transcribed spacer substitution rates across angiosperms: an approximate molecular clock with life history effects

Background  

A full understanding of the patterns and processes of biological diversification requires the dating of evolutionary events, yet the fossil record is inadequate for most lineages under study. Alternatively, a molecular clock approach, in which DNA or amino acid substitution rates are calibrated with fossils or geological/climatic events, can provide indirect estimates of clade ages and diversification rates. The utility of this approach depends on the rate constancy of molecular evolution at a genetic locus across time and across lineages. Although the nuclear ribosomal internal transcribed spacer region (nrITS) is increasingly being used to infer clade ages in plants, little is known about the sources or magnitude of variation in its substitution rate. Here, we systematically review the literature to assess substitution rate variation in nrITS among angiosperms, and we evaluate possible correlates of the variation.     

Approximate methods for estimating the pattern of nucleotide substitution and the variation of substitution rates among sites

We propose two approximate methods (one based on parsimony and one on pairwise sequence comparison) for estimating the pattern of nucleotide substitution and a parsimony-based method for estimating the gamma parameter for variable substitution rates among sites. The matrix of substitution rates that represents the substitution pattern can be recovered through its relationship with the observable matrix of site pattern frequences in pairwise sequence comparisons. In the parsimony approach, the ancestral sequences reconstructed by the parsimony algorithm were used, and the two sequences compared are those at the ends of a branch in the phylogenetic tree. The method for estimating the gamma parameter was based on a reinterpretation of the numbers of changes at sites inferred by parsimony. Three data sets were analyzed to examine the utility of the approximate methods compared with the more reliable likelihood methods. The new methods for estimating the substitution pattern were found to produce estimates quite similar to those obtained from the likelihood analyses. The new method for estimating the gamma parameter was effective in reducing the bias in conventional parsimony estimates, although it also overestimated the parameter. The approximate methods are computationally very fast and appear useful for analyzing large data sets, for which use of the likelihood method requires excessive computation.      

No variation and low synonymous substitution rates in coral mtDNA despite high nuclear variation

Background  

The mitochondrial DNA (mtDNA) of most animals evolves more rapidly than nuclear DNA, and often shows higher levels of intraspecific polymorphism and population subdivision. The mtDNA of anthozoans (corals, sea fans, and their kin), by contrast, appears to evolve slowly. Slow mtDNA evolution has been reported for several anthozoans, however this slow pace has been difficult to put in phylogenetic context without parallel surveys of nuclear variation or calibrated rates of synonymous substitution that could permit quantitative rate comparisons across taxa. Here, I survey variation in the coding region of a mitochondrial gene from a coral species (Balanophyllia elegans) known to possess high levels of nuclear gene variation, and estimate synonymous rates of mtDNA substitution by comparison to another coral (Tubastrea coccinea).     

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.     

Extensive variation in synonymous substitution rates in mitochondrial genes of seed plants

Background  

It has long been known that rates of synonymous substitutions are unusually low in mitochondrial genes of flowering and other land plants. Although two dramatic exceptions to this pattern have recently been reported, it is unclear how often major increases in substitution rates occur during plant mitochondrial evolution and what the overall magnitude of substitution rate variation is across plants.     

Calibrating molecular estimates of substitution rates and divergence times in birds

Many evolutionary studies of birds rely on the estimation of molecular divergence times and substitution rates. In order to perform such analyses, it is necessary to incorporate some form of calibration information: a known substitution rate, radiometric ages of heterochronous sequences, or inferred ages of lineage splitting events. All three of these techniques have been employed in avian molecular studies, but their usage has not been entirely satisfactory. For example, the 'traditional' avian mitochondrial substitution rate of 2% per million years is frequently adopted without acknowledgement of the associated uncertainty. Similarly, fossil and biogeographic information is almost always converted into an errorless calibration point. In both cases, the resulting estimates of divergence times and substitution rates will be artificially precise, which has a considerable impact on hypothesis testing. In addition, using such a simplistic approach to calibration discards much of the information offered by the fossil record. A number of more sophisticated calibration methods have recently been introduced, culminating in the development of probability distribution-based calibrations. In this article, I discuss the use of this new class of methods and offer guidelines for choosing a calibration technique.     

Adaptive significance of a circadian clock: temporal segregation of activities reduces intrinsic competitive inferiority in Drosophila parasitoids

Most organisms show self-sustained circadian oscillations or biological clocks which control their daily fluctuations in behavioural and physiological activities. While extensive progress has been made in understanding the molecular mechanisms of biological clocks, there have been few clear demonstrations of the fitness value of endogenous rhythms. This study investigated the adaptive significance of circadian rhythms in a Drosophila parasitoid community. The activity rhythms of three sympatric Drosophila parasitoids are out of phase, the competitively inferior parasitoid species being active earlier than the superior competitor. This temporal segregation appears at least partially determined by endogenous periods of the clock which also vary between species and which correlate the time of activity. This earlier activity of the inferior competitor significantly reduces its intrinsic competitive disadvantage when multiparasitism occurs, thus suggesting that natural selection acting on the phase of the rhythm could substantially deviate the endogenous period from the optimal ca. 24 h period. This study demonstrates that temporal segregation of competing species could be endogenously controlled, which undoubtedly favours their coexistence in nature and also shows how natural selection can act on biological clocks to shape daily activity patterns.     

The biological clock: the bodyguard of temporal homeostasis

In order for any organism to function properly, it is crucial that it be table to control the timing of its biological functions. An internal biological clock, located, in mammals, in the suprachiasmatic nucleus of the hypothalamus (SCN), therefore carefully guards this temporal homeostasis by delivering its message of time throughout the body. In view of the large variety of body functions (behavioral, physiological, and endocrine) as well as the large variety in their preferred time of main activity along the light:dark cycle, it seems logical to envision different means of time distribution by the SCN. In the present review, we propose that even though it presents a unimodal circadian rhythm of general electrical and metabolic activity, the SCN seems to use several sorts of output connections that are active at different times along the light: dark cycle to control the rhythmic expression of different body functions. Although the SCN is suggested to use diffusion of synchronizing factors in the rhythmic control of behavioral functions, it also needs neuronal connections for the control of endocrine functions. The distribution of the time-of-day message to neuroendocrine systems is either directly onto endocrine neurons or via intermediate neurons located in specific SCN targets. In addition, the SCN uses its connections with the autonomic nervous system for spreading its time-of-day message, either by setting the sensitivity of endocrine glands (i.e., thyroid, adrenal, ovary) or by directly controlling an endocrine output (i.e., melatonin synthesis). Moreover, the SCN seems to use different neurotransmitters released at different times along the light: dark cycle for each of the different connection types presented. Clearly, the temporal homeostasis of endocrine functions results from a diverse set of biological clock outputs.     

Genetic and molecular variation in the RpII215 region of Drosophila melanogaster

Molecular Genetics and Genomics - The RpII215 region of the X chromosome of Drosophila melanogaster was investigated to identify genetic functions and correlate these with the known molecular...     

In search of clinal variation in the period and clock timing genes in Australian Drosophila melanogaster populations

Clinal variation for repeat number in the Thr-Gly region of the period circadian timing gene in Drosophila melanogaster was described in Europe and has subsequently been used as evidence of thermal selection on period alleles. To test for clinal variation in this gene along the east coast of Australia, the period polymorphism was scored on flies from multiple samples collected repeatedly over a 5-year interval, along with variation at another circadian rhythm locus, clock. For period, there was no consistent evidence of clinal variation in the 17 and/or 20 repeat alleles, although when average allele length was examined a weak consistent clinal pattern was detected. For clock there was no evidence of clinal variation in the two most common alleles or in average repeat size. These data are inconsistent with the reported patterns in Europe and suggest that clinal variation in timing genes needs to be re-examined in this region.     

Size and shape heritability in natural populations of Drosophila mediopunctata: temporal and microgeographical variation

‘Traditional morphometrics’ allows us to decompose morphological variation into its major independent sources, identifying them usually as size and shape. To compare and investigate the properties of size and shape in natural populations of Drosophila mediopunctata, estimating their heritabilities and analysing their temporal and microgeographic changes, we carried out collections on seven occasions in Parque Nacional do Itatiaia, Brazil. In one of these collections, we took samples from five different altitudes. Measurements were taken from wild caught inseminated females and up to three of their laboratory‐reared daughters. Through a principal component analysis, three major sources of variation were identified as due to size (the first one) and shape (the remaining two). The overall amount of variation among laboratory flies was about half of that observed among wild flies and this reduction was primarily due to size. Shape variation was about the same under natural and artificial conditions. A genetic altitudinal cline was detected for size and shape, although altitude explained only a small part of their variation. Differences among collections were detected both for size and shape in wild and laboratory flies, but no simple pattern emerged. Shape variation had high heritability in nature, close to or above 40% and did not vary significantly temporally. Although on the overall size heritability (18 ± 6%)was significant its estimates were not consistent along months – they were non‐significant in all but one month, when it reached a value of 51 ± 11%. Overall, this suggests that size and shape have different genetic properties. This revised version was published online in July 2006 with corrections to the Cover Date.     

Spatial and temporal variation of microbial respiration rates in a blackwater stream

1. The extent of spatial and temporal variation of microbial respiration was determined in a first-order, sand-bottomed, blackwater stream on the coastal plain of south-eastern Virginia, U.S.A.
2. Annual mean respiration rates (as g O₂ m^–3 h^–1) differed significantly among substrata: leaf litter, 12.9; woody debris, 2.4; surface sediment, 0.8; hyporheic sediment, 0.4; water column, 0.003. Rates associated with wood were higher than those with leaves when expressed per unit surface area.
3. Highest respiration rates on leaves, wood and in the water column occurred during the summer, whereas rates in the sediments were greatest during the late autumn and winter. Water temperature, as well as particulate organic matter and nitrogen content of the substrata, was correlated positively with respiration rates.
4. A stepwise multiple regression showed that temperature and nitrogen content together explained 88% of the variation in respiration rates of leaves and wood. In contrast, particulate organic matter content and nitrogen content explained 89–90% of the variation in respiration in the sediments. Although water temperature was a significant factor in the sediment multiple regressions, its addition as an independent variable improved the regression models only slightly.
5. Annual mean respiration in the stream channel, based on the proportional amount of respiration occurring associated with each type of substratum during each month, was 1.1 kg O₂ m^–2 yr^–1. Seventy per cent of respiration in the stream occurred in the hyporheic zone, 8–13% occurred in the surface sediment, leaf litter or woody debris, and < 1% occurred in the water column. Approximately 16% of total detritus, or 40% of non-woody detritus, stored in the stream during the year was lost to microbial respiration.