Long-term Substitution Rates Research Articles

Temperature predicts the rate of molecular evolution in Australian Eugongylinae skinks.

Temperature differences over time and space have been hypothesized to cause variation in the rate of molecular evolution of species, but empirical evidence is mixed. To further test this hypothesis, we utilized a large exon-capture sequence data of Australian Eugongylinae skinks, exemplifying a radiation of temperature-sensitive ectotherms spanning a large latitudinal gradient. The association between temperature (and other species traits) and long-term substitution rate was assessed based on 1268 sequenced exons of 44 species pairs from the Eugongylinae subfamily using regression analyses. Temperature is the strongest, positively correlated predictor of variation in substitution rate across the Australian Eugongylinae. It explains 45% of variation in synonymous substitution rate, and 11% after controlling for all the other factors. Synonymous substitution rate is also negatively associated with body size, with a 6% variation explained by body size after controlling for the effects of temperature. Other factors are not associated with synonymous substitution rate after controlling for temperature. Overall, this study points to temperature as a strong predictor of the molecular evolution rate in the Eugongylinae subfamily, and demonstrates the power of large-scale exonic data to identify correlates of the rate of molecular evolution.

Ancient Endogenous Pararetroviruses in Oryza Genomes Provide Insights into the Heterogeneity of Viral Gene Macroevolution.

Endogenous viral sequences in eukaryotic genomes, such as those derived from plant pararetroviruses (PRVs), can serve as genomic fossils to study viral macroevolution. Many aspects of viral evolutionary rates are heterogeneous, including substitution rate differences between genes. However, the evolutionary dynamics of this viral gene rate heterogeneity (GRH) have been rarely examined. Characterizing such GRH may help to elucidate viral adaptive evolution. In this study, based on robust phylogenetic analysis, we determined an ancient endogenous PRV group in Oryza genomes in the range of being 2.41–15.00 Myr old. We subsequently used this ancient endogenous PRV group and three younger groups to estimate the GRH of PRVs. Long-term substitution rates for the most conserved gene and a divergent gene were 2.69 × 10−8 to 8.07 × 10−8 and 4.72 × 10−8 to 1.42 × 10−7 substitutions/site/year, respectively. On the basis of a direct comparison, a long-term GRH of 1.83-fold was identified between these two genes, which is unexpectedly low and lower than the short-term GRH (>3.40-fold) of PRVs calculated using published data. The lower long-term GRH of PRVs was due to the slightly faster rate decay of divergent genes than of conserved genes during evolution. To the best of our knowledge, we quantified for the first time the long-term GRH of viral genes using paleovirological analyses, and proposed that the GRH of PRVs might be heterogeneous on time scales (time-dependent GRH). Our findings provide special insights into viral gene macroevolution and should encourage a more detailed examination of the viral GRH.

Global Rate Variation in Bony Vertebrates.

This study investigated long-term substitution rate differences using three calibration points, divergences between lobe-finned vertebrates and ray-finned fish, between mammals and sauropsids, and between holosteans (gar and bowfin) and teleost fish with amino acid sequence data of 625 genes for 25 bony vertebrates. The result showed that the substitution rate was two to three times higher in the stem branches of lobe-finned vertebrates before the mammal-sauropsid divergence than in amniotes. The rate in the stem branch of ray-finned fish before the holostean-teleost fish divergence was also a few times higher than the holostean rate, whereas it was similar to or somewhat slower than the teleost fish rate. The phylogenetic relationship of coelacanth and lungfish with tetrapod was difficult to determine because of the short interval of the divergences. Considering the high rate in the stem branches, the divergences of coelacanth and lungfish from the stem branch were estimated as 408–427 Ma and 399–414 Ma, respectively, with the interval of 9–13 Myr. With the external calibration of the mammal-sauropsid split, the estimated times for ordinal divergences within eutherian mammals tend to be smaller than those in previous studies that used the calibration points within the lineage, with deeper divergences before the Cretaceous–Paleogene boundary and shallower ones after the boundary. In contrast the estimated times within birds were larger than those of previous studies, with the divergence between Galliformes and Anseriformes ∼80 Ma and that between Galloanserae and Neoaves 110 Ma.

Towards inferring the global movement of beak and feather disease virus

Beak and feather disease virus (BFDV) is a circular single-stranded DNA virus that causes psittacine beak and feather disease. We analysed 184 publically available BFDV full genomes to infer both the approximate geographical origin of the most recent common ancestor (MRCA) of these sequences and past BFDV long-range migrations using a Bayesian phylogeographic analyses. While the analysed BFDV sequences were sampled over too brief a period to ensure a strong enough temporal signal for accurate long-term substitution rate estimation, we were nevertheless able to identify Australia as the most likely location of the MRCA; A finding consistent with historical records of BFDV incidence. We additionally identified various trans-global BFDV movements including a number from Europe to regions of the world where psittacines are naturally found. This is concerning because it suggests that any BFDV variants that might emerge in captive European birds could directly threaten wild psittacine populations.

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.

Genomic fossils calibrate the long-term evolution of hepadnaviruses.

Author SummaryPaleovirology is the study of ancient viruses and the way they have shaped the innate immune system of their hosts over millions of years. One way to reconstruct the deep evolution of viruses is to search for viral sequences “fossilized” at different evolutionary time points in the genome of their hosts. Besides retroviruses, few virus families are known to have deposited molecular relics in their host's genomes. Here we report on the discovery of multiple fragments of viruses belonging to the Hepadnaviridae family (which includes the human hepatitis B viruses) fossilized in the genome of the zebra finch. We show that some of these fragments infiltrated the germline genome of passerine birds more than 19 million years ago, which implies that hepadnaviruses are much older than previously thought. Based on this age, we can infer a long-term avian hepadnavirus substitution rate, which is a 1,000-fold slower than all short-term substitution rates calculated based on extant hepadnavirus sequences. These results call for a reevaluation of the long-term evolution of Hepadnaviridae, and indicate that some exogenous hepadnaviruses may still be circulating today in various passerine birds.

Molecular clocks: when timesare a-changin'

The molecular clock has proved to be extremely valuable in placing timescales on evolutionary events that would otherwise be difficult to date. However, debate has arisen about the considerable disparities between molecular and palaeontological or archaeological dates, and about the remarkably high mutation rates inferred in pedigree studies. We argue that these debates can be largely resolved by reference to the "time dependency of molecular rates", a recent hypothesis positing that short-term mutation rates and long-term substitution rates are related by a monotonic decline from the former to the latter. Accordingly, the extrapolation of rates across different timescales will result in invalid date estimates. We examine the impact of this hypothesis with respect to various fields, including human evolution, animal domestication and conservation genetics. We conclude that many studies involving recent divergence events will need to be reconsidered.

Time Dependency of Molecular Rate Estimates and Systematic Overestimation of Recent Divergence Times

Studies of molecular evolutionary rates have yielded a wide range of rate estimates for various genes and taxa. Recent studies based on population-level and pedigree data have produced remarkably high estimates of mutation rate, which strongly contrast with substitution rates inferred in phylogenetic (species-level) studies. Using Bayesian analysis with a relaxed-clock model, we estimated rates for three groups of mitochondrial data: avian protein-coding genes, primate protein-coding genes, and primate d-loop sequences. In all three cases, we found a measurable transition between the high, short-term (< 1-2 Myr) mutation rate and the low, long-term substitution rate. The relationship between the age of the calibration and the rate of change can be described by a vertically translated exponential decay curve, which may be used for correcting molecular date estimates. The phylogenetic substitution rates in mitochondria are approximately 0.5% per million years for avian protein-coding sequences and 1.5% per million years for primate protein-coding and d-loop sequences. Further analyses showed that purifying selection offers the most convincing explanation for the observed relationship between the estimated rate and the depth of the calibration. We rule out the possibility that it is a spurious result arising from sequence errors, and find it unlikely that the apparent decline in rates over time is caused by mutational saturation. Using a rate curve estimated from the d-loop data, several dates for last common ancestors were calculated: modern humans and Neandertals (354 ka; 222-705 ka), Neandertals (108 ka; 70-156 ka), and modern humans (76 ka; 47-110 ka). If the rate curve for a particular taxonomic group can be accurately estimated, it can be a useful tool for correcting divergence date estimates by taking the rate decay into account. Our results show that it is invalid to extrapolate molecular rates of change across different evolutionary timescales, which has important consequences for studies of populations, domestication, conservation genetics, and human evolution.