pathway and several other complex biochemical systems such as the mechanism of the bacterial flagella. Bethe contends that these complex biochemical systems cannot be broken down into a series of (forward or backward) steps subject to Darwinian evolution. He maintains that their evolution is totally inexplicable in terms of standard evolutionary theory or indeed any scientific theory. Bethe’s solution is either radical or hopelessly archaic depending on your point of view; he proposes that the existence of complex biochemical systems is due to God’s intervention in the evolution of life on Earth.
A third problem for the standard evolutionary theory is the apparent existence of a heretical type of mutation. Standard neoDarwinian evolutionary theory predicts that mutations occur randomly with no respect to the direction of evolutionary change. Natural selection provides the direction of evolution by selecting hosts with beneficial mutations; but those mutations are generated randomly. This does not mean that all sites in DNA have the same mutation rate. In fact we know that there are regions in most chromosomes that are highly mutable (probably due to their local chemical environment, or because they bind mutation-promoting proteins). However, it does mean that the mechanisms that introduce mutations into DNA are presumed not to know which bases are likely to generate advantageous mutations if they mutate.
Nonetheless, when John Cairns of the Harvard School of Public Health in Boston set out to test this reasonable premise he found things were not quite so simple. Cairns incubated cells of the common gut bacterium E. coli in conditions where a single mutation could rescue them from starvation. He used an E. coli lac- strain deficient in an enzyme called β-galactosidase (β-gal) needed for the cells to eat lactose (milk sugar). He then fed the cells on a diet of only lactose. Without β-gal he expected all the cells to starve. In fact it takes a lot to kill E. coli by starvation, mostly the cells just shut up shop and go into what is called a stationary phase, where either they don’t replicate or only very slowly. E. coli cells can survive for many weeks in this stationary phase.
Cairns fed a parallel culture of E. coli cells on yeast extract, which the cells could eat without need for the β-gal enzyme. The standard neoDarwinian theory would predict that the mutation lac- → lac+, to generate a fully functional β-gal enzyme, should occur at the same rate for the cells fed on yeast extract, compared with cells on the starvation diet of lactose. The only difference should be that, for the cells fed only on lactose, the mutation would rescue them from starvation; whereas the mutation would be irrelevant for the cells happily feeding on the yeast extract. What Cairns actually found was a much higher rate of lac- → lac+ mutation when the cells had only lactose to eat. Cairns examined other genes but their rate of mutation was unchanged by starvation, indicating that the phenomenon was not caused by a general increase in mutation rate.
These adaptive mutations suggested that a starving cell could sense that it was starving and somehow choose the gene it needed to mutate to save itself from starvation. Cairns’ paper describing adaptive mutations was published in Nature in 19884, unleashing a storm of controversy. The difficulty was that there was no known mechanism which could allow the environment of a living cell to influence the targeting of DNA mutations. The direction of information flow in the cell is from DNA through RNA to protein and outwards to the environment. There is currently no known mechanisms by which information can flow backwards from the environment to DNA to account for these mutations.
Since 1988, hundreds of publications have appeared that have either supported or denied the phenomenon of adaptive mutations. Adaptive mutations have been proposed to occur in many types of bacteria as well as more complex yeast and animal cells and have even been implicated in cancer. One of the most impressive demonstrations of the phenomenon was by Barry Hall of Rochester University who demonstrated that two sites just a few bases apart on the same DNA molecule could be subject to widely different mutation rates, dependent on whether or not those mutations were adaptive5. Whatever their mechanisms, adaptive mutations appear to be able to bias the mutational process to favour certain genetic changes.
I must emphasize that though there may be some doubt concerning the mechanisms involved in evolutionary change (and there are likely to be many), this should not be confused with any doubt concerning the process of evolution itself. There is overwhelming molecular evidence that all modern species have evolved from earlier species. Indeed, there is considerable evidence that we have all evolved from a single ancestral cell. Let us next examine the probable nature of that common ancestor.
THE PROTO-CELL
Molecular evolutionary studies have established the existence of the major domains, but what kind of creature was the ancestor of the Archaea, eubacteria and eukaryotes: the proto-cell? That there was indeed a single common ancestor of all cellular life is indicated by the number of features we all have in common (DNA, RNA, ribosomes, the genetic code); but what did that proto-cell look like? How did it live?
We can make an estimate of how many genes the proto-cell is likely to have possessed by counting the number of genes found in all three domains of life. The simplest explanation for the presence of common genes is that they reflect a common inheritance from the proto-cell. Scientists who have examined genes from each of the three domains estimate that there are eight hundred to a thousand ancient conserved regions (ACRs) in modern proteins.6
Surprisingly perhaps, eight hundred to a thousand genes is a little more than the number of genes present in the genome of a living bacterium, Mycoplasma genitalium. This organism causes non-gonoccocal urethritis (inflammation of the urethra which is not gonorrhoea) and respiratory infections in humans, and has the smallest known genome of any living creature. Its entire chromosome of 580,070 DNA bases has been sequenced and found to code for only four hundred and seventy proteins. However, this microbe is not really a free-living organism – it lacks the enzymes necessary to make many essential biochemicals. It barely manages to replicate under very cosseted laboratory conditions. It is actually a highly evolved parasite that relies on our cells to do much of its biosynthetic hard work. It is not a feasible proto-cell. Nevertheless we will accept a lower estimate of about five hundred genes as the minimum number of genes likely to have been present in the last common ancestor of all cellular life, the proto-cell.
But what was the proto-cell like? We can approach this question by examining the characteristics of the deepest branches of the rRNA tree. For instance, the deepest branching Archaea are thermophilic bacteria that breathe sulfur compounds. The deepest branches of the eubacterial domain are thermophilic (heat-loving), sulfur-utilizing photosynthetic bacteria; suggesting that the proto-eubacterium was an anaerobic photosynthetic cell. Most researchers do not think it likely that photosynthesis evolved very early in life. It is a highly complex reaction that requires the co-operative action of many enzymes. The more ancestral characteristics are likely to be closer to the Archaea that use the energy of sulfur compounds directly to fix carbon dioxide. On this basis, the likely characteristics of the proto-cell were probably similar to the Archaea, suggesting it lived in a hot, sulfurous, oxygen-free environment and it used sulfur to fix carbon dioxide.
But when did the proto-cell live? Do the conditions we have described correspond to the likely environment where it emerged?
THE FIRST FOSSILS
The first undisputed evidence of life is in rocks about three and a half billion years old. Large circular structures called stromatolites (from the Greek meaning ‘stony carpet’) are present in fine-grained flint-like sedimentary rock7 called chert. Some of these rocks contain curious white concentric rings about a metre across. Nobody knew the origin of these structures
