Time-dependent rates of molecular evolution

Abstract

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.

The origins of the enigmatic Falkland Islands wolf

“…The accuracy of molecular divergence date estimates is directly related to the quality of calibration data, and their proximity to the date of interest. In this regard, the use of deep fossil calibration points has been shown to be inappropriate for intra-specific and recent inter-specific divergences 18,19 , such as those within Dusicyon. The radiocarbon dates associated with the ancient sequences of D. avus provide much closer calibration points to the late Pleistocene events under consideration than the early canid fossils used in Slater et al 7 , and importantly do not suffer from the same uncertainty over taxonomic identification and phylogenetic position.…”

“…To examine the problems caused by the temporal dependency of molecular dates, we performed molecular dating analyses using either internal (radiocarbon), or external (fossil), dates. The advantages of using internal calibrations to study recent evolutionary events are well established 18,19 , and given a divergence event thought to be late Pleistocene (natural dispersal) or Holocene (human dispersal), the internal radiocarbon dates for D. avus appear far more appropriate than external fossil dates of 4-32 Ma (with largely unknown error margins) and uncertain taxonomic/ phylogenetic position.…”

“…However, even if this date estimate was approximately accurate, the colonization event could have been considerably older or younger than this depending on the demographic history, any subsequent lineage extinctions 16 , and the relationship between the FIW and unsampled mainland relatives 17 . Furthermore, the use of external fossil calibrations to date recent events is known to be problematic due to the temporal dependency of molecular rates 18,19 . Either way, while the estimated 330 ka date and wide error margins (70-640 ka) clearly predates human arrival, it provided little evidence as to how the FIW might have colonized the islands.…”

Increased mitochondrial mutation frequency after an island colonization: positive selection or accumulation of slightly deleterious mutations?

“…However, it has been suggested that there is a time dependence of substitution rates that can influence the estimation of the age of splitting events [2]. More recently separated populations show generally higher rates, while rates between long separated populations (greater than 1 Myr) converge to a lower level.…”

Estimating time to the most recent common ancestor (TMRCA): comparison and application of eight methods

“…However, we highlight the possibility that the choice of mutation rates can bias the estimation of divergence time, especially as (1) evolutionary rates may actually be time dependent and (2) the evolutionary rate estimate can depend on the timescale of measurement. 29 A comprehensive characterization of time-dependent biases in evolutionary rate is likely to be important but regretfully beyond the scope of the current study.…”