Finagle’s Constant is whimsically defined as “that quantity which, when added to, subtracted from, multiplied by, or divided by the answer you got, gives you the answer you should have gotten.” One of the best examples in modern science is the so-called “Molecular Clock” hypothesis in evolutionary theory.
In Current Biology, Michael S. Y. Lee and Simon Y. W. Ho teach the uninitiated about the wizardry that goes into molecular clocks. First, a bit of history.
In the 1960s, several groups of scientists, including Emile Zuckerkandl and Linus Pauling, had noted that proteins experience amino acid replacements at a surprisingly consistent rate across very different species. This presumed single, uniform rate of genetic evolution was subsequently described using the term ‘molecular clock’. Biologists quickly realised that such a universal pacemaker could be used as a yardstick for measuring the timescale of evolutionary divergences: estimating the rate of amino acid exchanges per unit of time and applying it to protein differences across a range of organisms would allow deduction of the divergence times of their respective lineages…. [Emphasis added]
Remember this: at first, biologists assumed they had discovered a reliable timepiece. Great, they thought; now we can watch Darwin’s tree of life unfold over time. This new clock would show the sequence of great transformations: when animals emerged from the sea, when flowering plants blossomed on land, and when the ancestors of great whales began swimming. Unfortunately, as with many things in biology, complications soon set in.
In the 50 years since, leaps in genomic sequencing technology and new computational tools have revealed a more complex and interesting reality: the rates of genetic change vary greatly across the tree of life. The term ‘molecular clock’ is now used more broadly to refer to a suite of methods and models that assess how rates of genetic evolution vary across the tree of life, and use this information to put an absolute timescale on this tree. Modern molecular clocks are thus critical to inferring evolutionary timescales and understanding the process of genetic change. Analyses of genomic data using clock models that accommodate variation in evolutionary rates have shed new light on the tree of life, as well as the organismal and environmental factors driving genetic change along its branches. However, some major theoretical, empirical and computational challenges remain.
It’s not a clock then. It’s not reliable. The genetic changes tick at wildly different rates. Ah, but the promise of “shedding light” on evolution was too tempting to let it go. With a few tweaks and new assumptions — a little finagling — molecular clocks might still prove useful. We’ll just give the variations an impressive-sounding name. How about “rate heterogeneity”?
Modern molecular clocks can handle various forms of evolutionary rate heterogeneity. Rates can vary across different parts of the genome (site effects), across taxa (lineage effects), and across time (here termed ‘epoch effects’).
Moving along, Ho and Lee engage in some rationalizations for stretching, compressing, and force-fitting wildly different clock rates into Darwin’s tree. It’s reminiscent of naughty Johnny telling more and more lies to back up the first one.
An extra layer of interest and complexity emerges when two or more sources of rate heterogeneity interact. Site and lineage effects interact when different genes have different patterns of rate variability across taxa (Figure 2D). Mitochondrial DNA has greatly accelerated rates of evolution in snakes and dragon lizards compared with typical lizards, but nuclear DNA shows no such trend. Genomic analyses suggest that such interactions are widespread. Selection might be relaxed on particular genes in particular taxa and thus lead to rapid molecular evolution. For example, the genes coding for tooth enamel are no longer under stabilizing selection in toothless mammals such as anteaters and sloths. Thus, those genes evolve much more rapidly in these lineages, but this pattern is not seen for most other genes. Such complex patterns of rate variation can be accommodated using partitioned clock models, where different portions of the genome are recognized as evolving according to separate clocks or ‘pacemakers’.
There is one fixed star that keeps the finaglers on target: the fossil record. It reliably shows the divergence times and patterns over evolutionary history. But wait. Wasn’t the molecular clock supposed to be the yardstick for the fossil record? Which clock is calibrating which?
Molecular clocks are vital to reconstructing the detailed timescale and branching pattern of the tree of life, especially in soft-bodied groups that have left few or no fossils. In turn, this can shed light on how major evolutionary events have been influenced by Earth history. However, the use of inappropriate clock models or erroneous calibrations can produce highly misleading estimates of evolutionary timescales. These issues have led to vigorous debates about the timing and drivers of major evolutionary events, including the origins of animal phyla, the ordinal divergences of birds and mammals or the radiation of flowering plants.
The “origins of animal phyla” — this brings them to the Cambrian explosion. As an example of many spectacular differences between molecular clocks and fossil-record clocks, Ho and Lee point to molecular estimates that put the emergence of animal phyla “a billion years ago — nearly twice the age of the explosion of animal fossils in Cambrian rocks.” Now what to do? Evolutionists tried to compress the rates as far as they could, but it wasn’t enough.
These results were at least partly driven by failure to account for lineage effects: genetic change generally occurs more slowly in vertebrates than in invertebrates, but early molecular analyses extrapolated the slow vertebrate evolutionary rate across the entire animal tree. This caused the estimates of animal divergence times to be stretched deep into the Precambrian. Subsequent analyses with better models of rate variation and more carefully chosen calibrations moved the initial radiation of animals to a later time — into the early Ediacaran period, when the world was gripped by several massive glaciation events (‘snowball earth’). Nevertheless, this still precedes the first definitive metazoan fossils by tens of millions of years.
One pattern does emerge; molecular divergence times are generally older than fossil divergence times. But with flexible clocks, how can one know which to rely on? The situation resembles the folk tale about the town crier who set his watch by the church bell, only to find out the bell ringer calibrated his tolling by the town crier’s call.
The fixed star on which both methods rely is actually neither one: it is the assumption of Darwin’s tree of life. With that in mind, watch this:
One intriguing but largely untested suggestion is that molecular evolution might occur much more rapidly during evolutionary radiations, leading to big genetic divergences in short time intervals. This would be likely to cause current clock models to overestimate divergence ages…. The link between higher rates of evolution and evolutionary success might prove to be more general, and relevant for phenotypic as well as genetic traits.
Mr. slow-and-gradual Darwin might be scandalized by the notion that evolution could be rapid, but he would be gratified to know that finagling a few assumptions can leave his tree intact.
In sum, what we were told would provide empirical evidence for evolution actually has morphed into a set of assumptions and methods to calculate different Finagle’s Constants for each part of Darwin’s tree, in order to keep the picture from getting falsified. Empiricism must yield to that requirement.
Lee and Ho end by saying, “we can choose to identify and analyse only the genes that display the most desirable of evolutionary timescales.” On the other hand, “Instead, more room for improvement might lie in developing better models of rate variation and refining our knowledge and use of calibrations.” Each animal, each lineage, each gene, and each epoch are now going to need their own calibration method, based on what is needed to keep the Tree of Life from falling. “For these reasons, molecular clocks will continue to play a key role in shaping our understanding of the evolution of life and the genes that code for it.”
For more on problems with the molecular clock hypothesis, see here on the Cambrian explosion, Casey Luskin on placental mammals and biogeography, and Stephen Meyer’s analysis of “lightning-fast evolution” to explain the Cambrian enigma.
Image credit: © sv_photo — stock.adobe.com.