Is our clock ticking at the right pace?

This week’s post is a guest contribution by Gustavo Bravo, who recently finished his Ph.D. at the Louisiana State University Museum of Natural Science , working on the systematics and diversification of the Neotropical bird family Thamnophilidae. 

A pervasive goal in evolutionary biology is to elucidate the history of living organisms on Earth. Because we are often interested in knowing when different lineages might have originated, we use different resources to date speciation events as accurately as possible. One of these tools is the “molecular clock”, which is a technique that relies on the rates of nucleotide (DNA) or amino acid (protein) change to infer the timing of events in the distant past. The idea behind the molecular clock is that over time a DNA fragment may accumulate mutations at a constant rate, or in “clock-like” fashion as it is commonly referred to. Therefore, the number of substitutions in a DNA fragment between two different organisms might be proportional to the amount of time since they diverged from each other.

There are two ways in which we can translate the number of substitutions between a pair of lineages into absolute dates. First, we can calibrate the clock against absolute times resulting from independent evidence such as fossil or geological dates. And secondly, we can measure directly the rate of mutation by comparing DNA or protein sequence data in present day organisms. Because the fossil record for some groups is incomplete and the dating of geological events remains controversial, some of those clocks are likely to produce inaccurate estimates of time.

For instance, in phylogenetic and biogeographic studies of Neotropical organisms the closure of the Isthmus of Panama is often taken as calibration point for the molecular clock (e.g. Weir 2008) assuming that it took place between around 3.5 mya (Coates and Obando 1996). A vast portion of our current knowledge on the biogeography and evolutionary history of these groups relies upon those clocks. However, recent geological data suggest that the closure of the canal might be much older than that (ca. 15 my; e.g. Farris et al. 2011), which would imply that many of the things we think we know are not entirely correct. A final consensus is far from being reached, but a case like this makes directly measuring mutation rates an interesting opportunity to look into the past. This is usually possible when studying evolution of organisms with short life spans and good population sizes (too bad it is almost impossible in many groups!).

In the field of human evolution, recent studies reexamined the fossil–calibrated molecular clock (split between apes and Old World monkeys) that we have been using over the last couple of decades (10-9 bp-1 year-1; Takahata et al. 1997) by producing genome-wide direct measurements of human mutation rates (reviewed by Scally and Durbin 2012 and Gibbons 2012). One of these studies estimated that there are, in average, 36 spontaneous mutations in babies (i.e. mutations not inherited from either parent), and when a mean generation time in humans of 25 years was assumed, it was possible to calculate a new molecular clock. All of these studies coincide in a molecular clock for humans slower than what we previously thought, and most studies coincide in a clock approximately half of our previous estimate (listen here to Science Podcast with A. Gibbons).

This new rate tells that human evolution has occurred at a much slower pace than we previously thought. Thus, it has interesting implications for knowing when key events in the history of humans took place. Not surprisingly, some of these new estimates are in agreement with information from the fossil record, whereas others are not. For instance, date estimates using the new mutation rate are in agreement with the fossil record regarding the Human-Neandertal split (400,000–600,000 ya) and the Out-of-Africa migration (90,000–130,000 ya), but disagree in the Human-orangutan split (34–46 mya vs. 9–13 mya) and in the Human–chimpanzee split (8–10 mya vs. 4.1–7 mya). Estimates based on the fossil–calibrated clock show an inverse pattern; they coincide with the fossil record in the Human-orangutan and Human–chimpanzee splits, and differ in the Human-Neandertal split and the Out-of-Africa migration.

This discordance could be explained by several reasons affecting the estimation of both molecular clocks. For instance, the use of only small regions of DNA, the lack of key fossils such as those for chimpanzees or gorillas, possible inaccurate dating of known fossils, or wrong identification of fossils of human ancestors could affect the estimates of the fossil-calibrated molecular clock. Likewise, the new molecular clock based on genome-wide mutation rates assumes that rates and generation times in humans correspond to those in chimpanzees and gorillas, and that they have remained constant over time. Regardless of what the actual cause of this discordance is, we are now one step closer to understanding human evolution.

The beauty of these new findings is that we have now more information and data to be tested and further evaluated. There is a lot of work to be done! We need to keep finding and studying fossils, we need to work on gathering genetic samples, we need to keep making our calculation of mutation rates more precise, and we need to keep making good use of new technologies. It is fascinating how we are often capable of broadening our perspectives on important questions of evolutionary biology, and at the same time realize that there is always something left to study. It never ceases to amaze me that biology is full of paradigm shifts that keep us highly entertained!


Coates A. G. & Obando J. A. 1996. The geologic evolution of the Central American isthmus. In: Evolution and Environment in Tropical America (eds Jackson J. B. C., Budd A. F., Coates A. G.), pp. 21–56. University of Chicago Press, Chicago, Illinois.

Farris, D.W., Jaramillo, C.A., Bayona, G.A., Restrepo- Moreno, S.A., Montes, C., Cardona, A., Mora, A., Speakman, R.J., Glasscock, M.D., Reiners, P., and Valencia, V., 2011, Fracturing of the Panamanian isthmus during initial collision with South America. Geology 39, 1007–1010

Gibbons, A. 2012. Turning Back the Clock: Slowing the Pace of Prehistory. Science 338, 189–191.

Scally, A. & Durbin, R. 2012. Revising the human mutation rate: implications for understanding human evolution. Nature Rev. Genet. 13, 745–753.

Takahata, N. & Satta, Y. 1997. Evolution of the primate lineage leading to modern humans: phylogenetic and demographic inferences from DNA sequences. Proc. Natl Acad. Sci. USA 94, 4811–4815.

Weir, J. T. & D. Schluter. 2008. Calibrating the avian molecular clock. Molecular Ecology 17: 2321–2328.

One comment on “Is our clock ticking at the right pace?

  1. Hird says:

    interesting post! this stuff hurts my brain. so we can directly estimate a parent -> offspring mutation rate (through whole genome sequencing) but how does that relate to a species level mutation rate? is it really as simple as (mutation rate/generation * generations/year = mutation rate/year)? i also wonder how conserved the mutation rate/generation is and on what (taxonomic or temporal) scale. dna replication is so cool!

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