Molecular Clockwork And Related Theories

Molecular clocks, a complex topic central to current debates on human evolution, first came into prominence in paleoanthropology in the 1960’s. One well-known study by Vincent Sarich and Alan Wilson of the University of California (1967) measured the immunological reactions in primates and other animals to a control sample of the blood protein serum albumin. The differences, assumed due to a constant rate of evolution through mutations, were then plotted on a linear scale showing time elapsed since each species diverged from a common ancestor.

On the same principle, DNA, the genetic reproductive molecule, is often used for inter-species comparison. Assuming a constant rate of mutation or random replacement of amino-acid codes in DNA, the time elapsed between descent from a common ancestor can be calculated by comparing DNA segments from many different animal populations, from sharks to chimpanzees. With access to a large genetic data base and a computer program for “best fit” distance trees, evolutionary histories or phylogenies can be constructed independently of the often problematic, gap-filled fossil record.

Increasingly, evolutionary biologists have employed the relatively simple genetic makeup of mitochondrial DNA (mtDNA) as an efficient form of molecular clock. Mitochondria, energy-producing organelles in cells, have their own DNA strands which, limited in function to mitochondrial reproduction, are significantly shorter than those in the nucleus of a cell. Mutations in the simpler mitochondrial DNA occur much faster than in nuclear DNA, compressing more evolutionary generations into less time. Adding to the appeal of mtDNA for tracking evolutionary history has been the wide consensus that, after conception, only the egg’s mitochondria survive, and mtDNA is therefore inherited only through the maternal line.

During the past 15 years, extensive searches have been made through genetic records to find a “Mitochondrial Eve” of all modern humans. A widely-publicized 1987 study by Cann, Stoneking, and Wilson (the latter, also an author of the 1967 serum albumin study) used mtDNA comparisons of 147 people from Europe, Africa, Asia, Australia, and new Guinea to show all present human mtDNA is descended from a single African woman of about 200,000 years ago.

This has caused considerable controversy over issues beginning with the chancy workings of population genetics. Famines and other catastrophic events about 200,000 years ago could have caused genetic bottlenecks or constrictions, eliminating older human ancestral lines. Today’s retrospective survey of mtDNA would then show only surviving types, misleadingly suggesting the human species evolved at that later time (Weiss and Mann 1990). Also involved is the independent nature of mtDNA itself, evolving distinctly in each individual from the nuclear DNA which is the criteria of speciation.
Comparisons based on nuclear DNA, for example, reveal chimps and humans to be closer than does mtDNA, which shows more similarities between chimps and gorillas. Finally, recent evidence (discussed below) suggests the assumption that mtDNA is only passed through the female line may itself be faulty.

The Mitochondrial Eve theory also seems to many researchers to be at variance with the fossil record, which shows widespread hominid migrations and variation after 2 million years ago (myr), well documented for Homo erectus in China, Java, and the Black Sea by 1.8-1.6 myr, and Archaic Homo sapiens and Neanderthals after 0.6 myr. According to the Mitochondrial Eve theory, all non-African H. erectus and H. neanderthalensis populations are unrelated to the evolution of anatomically modern humans (H. s. sapiens). This directly contradicts the “Regional Continuity” model used by many paleoanthropologists. In spite of such controversies, the Mitochondrial Eve theory has considerable scientific adherence and popular recognition. A new study by South African researchers, for example, proposes the most ancient mtDNA belongs to “Bushwomen” or Khoisan people. Recent genetic studies in China, meanwhile, lend support to “out of Africa” theories.

As masses of data accumulate from the statistically-oriented studies of mitochondrial biology, it is becoming apparent that the required methodology of studying mtDNA is anything but straightforward. Currently under fire is the once-canonical view that mtDNA is inherited only through the mother, now challenged by a set of studies reported in Proceedings of the Royal Society (7 March 1999) by Erika Hagelberg of Cambridge University, and Adam Eyre-Walker, Noel Smith and John Maynard Smith of Sussex University. It has long been known that paternal mitochondria can sometimes penetrate the human egg and survive for several hours. While studies of mice and other organisms have actually shown recombination between male and female mtDNA, evidence of mtDNA recombination in human populations has been very elusive.

Now such evidence appears to have been found in a mtDNA research project led by Erika Hagelberg on the tiny island of Nguna, in the archipelago of Vanuatu in Melanesia (west of Polynesia including the Solomon Islands and Fiji). Studying human migrations, Hagelberg and her colleagues were analyzing hundreds of people from Papua-New Guinea and Melanesia. MtDNA samples on Nguna Island showed, as expected, three main population groups from colonizations over thousands of years. But in all three there also occurred a single mutation previously only known from one northern European. Hagenberg and her colleagues (1999) think it highly improbable for such a rare mutation event to occur repeatedly in such an isolated location. A more likely explanation would be recombination between different mitochondrial DNA types.

Similar conclusions were drawn by Adam Eyre-Walker and his colleagues at Sussex University, from statistical analysis of “homeoplasies,” common mutations in mitochondrial proteins that occur in seemingly distinct lineages around the world. Assuming maternal inheritance only of mtDNA, these were thought to be “hypervariable” sites where mutations occurred with high frequency. Review of some European and African mtDNA sequences by Eyre-Walker et al., however, show no evidence that these sites are particularly variable over all lineages. Most of these mutations were found in only a limited geographic area, suggesting they occurred rarely and then spread locally by recombination, which appears a far more likely cause of the homeoplasies.

Such findings, if upheld, seriously complicate the basis of using mtDNA to provide straightforward genetic lines, such as assumed in the Mitochondrial Eve hypothesis. The surprising homogeneity in the mtDNA of modern humans interpreted, in the Mitochondrial Eve hypothesis, as resulting from a recent common ancestor, may simply show the dilution of mutations caused by the recombination of mtDNA.

Even occasional mixing of maternal and paternal genes would make it uncertain whether new traits in two different human lineages are due to two independent mutations or to the transfer of a mutation from one lineage to another by recombination. Recombinations could also add to or erase changes from mutations, thus blurring, as Hagelberg's team points out, the differences between mtDNA lineages. This would make any past evaluations of human history using mtDNA, including the Mitochondrial Eve theory, subject to cautious reinterpretation. This most directly impacts the time scale of Mitochondrial Eve, and seriously weakens the value mtDNA mutation rates as a molecular clock. Recombination with paternal mtDNA causing some variation in mtDNA would make its mutation rate much lower than biologists thought. Eyre-Walker notes Eve may have lived twice as long ago as current estimates.

The controversial recombination factor is providing new directions for research and interpretation. In 1997, Svante Pääbo of the Max Planck Institute of Evolutionary Anthropology in Leipzig retrieved Neanderthal DNA over 50,000 years old, which he determined to have not contributed in any way to the mtDNA of modern humans. But the possibility of recombination suggests to Erika Hagelberg that Neanderthals might be more closely related to modern humans than Pääbo’s mtDNA data shows. Pääbo partially agrees, but feels recombination has not yet been effectively proven. MtDNA shows Neanderthals equally distant from both modern Europeans, whom they may be ancestral to, and unrelated populations.

Further research on mtDNA evolution should serve to identify and eliminate the specific genes which mutate at abnormally fast or slow rates. Jody Hey and Eugene Harris of Rutgers University suggest that future work should increasingly concentrate on the more complex nuclear genes. A recent study by Hey and Harris (1999) on the mutation rate of PDHA1 genes in the X Chromosome, thought to have a steady rate of mutation, has identified two populations at least 200,000 years old ancestral to modern humans. To determine the mutation rate of the gene, these were compared to the differences between human and chimpanzee PDHA1 genes, diverging at least 5-6 million years ago. They found that prior to 200,000 years ago, one form of this gene existed only in Africa and led to types only in modern Africans. Another existed only outside of Africa with one variant found in some modern Africans and another which split ca. 200,000 years ago into two haplotypes found in non-Africans.

Milford Wolpoff of the University of Michigan, a long-time opponent of the oversimplified use of molecular clocks (1988), supports the recent findings of Hey and Harris. If this evidence is not to make “Out-of-Africa II” theories obsolete, they may nevertheless need to evolve significantly themselves, to accommodate Asian and European populations originating in Africa but leaving considerably earlier than 100,000 to 200,000 years ago.

[References: Cann, R.L., M. Stoneking and A.C. Wilson, Nature 325, 1987; Eyre-Walker, A., N.H. Smith, and J. Maynard Smith, Proc. Royal Society B, 1999, Vol.266, pp.477-483. Hagelberg, E. et al., Proc.Royal Society B, 1999 (vol 266, p. 485), Hey, J. and E. Harris, Proc. Natl. Academy of Sciences, 16 Mar. 1999; Ji et al., Nature 398, 1999; Kumar, S. and S.B. Hedges, Nature 392,1998; Merriweather, D.A. and F.A. Kaestle, Science 285, 1999; Sarich, V.M. and A.C. Wilson, Proc. Natl. Academy of Sciences 58, 1967; Weiss, M.L. and A.E. Mann, 1990, Human Biology and Behavior, Scott, Foresman; Wolpoff, M.H., et al, Science 241, 1988]

I wrote a short paper last year for a Course I took for my own edification.

It is elementary stuff, but some FReepers migh appreciate a few excerpts only.

I am no expert, but I found the subject to be fascinating. I am not trying to pass myself off as an Acedemic. I just like the subject, and below is a bit of what I put together. Some of (likely most of it) it obviously "lifted" from the Internet.

Mitochondria are small energy-producing organelles found in cells. Surprisingly, mitochondria have their own DNA molecules, entirely separate from our nuclear DNA. Most cells contain between 500 and 1000 copies of the mtDNA molecule, which makes it a lot easier to find and extract than nuclear DNA. In humans the mtDNA genome consists of about 16,000 base pairs (far shorter than our nuclear DNA), and has been completely sequenced. What makes mtDNA particularly interesting is that, unlike nuclear DNA which is equally inherited from both father and mother, mtDNA is inherited only from the mother, because all our mitochondria are descended from those in our mother's egg.

The DNA in mitochondria was first discovered in 1963. In that year, researchers discovered that mitochondria have their own DNA or "blueprint" (mtDNA), which is different than the nuclear DNA (nDNA) found in the cells' nucleus. It was noted that the mtDNA was distinct from the nuclear DNA found in the nucleus of cells. It is now believed that mitochondria contain their own DNA because millions of years ago they were once independent living organisms similar to today’s bacteria. ....

By comparing mutations in the DNA of people who live in different parts of the world, geneticists are developing new theories about how humans populated the Earth. The evidence points to a common African origin. Much of the work has been based upon maternal lines. The DNA of present-day Africans is more diverse than that of people of other continents, indicating that humans have lived there the longest. Traces of ancient African genes can be found in everyone living today....^.

The discovery of Mitochondrial DNA has lead to numerous new hypothesis concerning the nature and history of humans. Researchers have discovered many new paths which are currently being followed. Some of these R&D programs are hoped will help in a greater understanding of metabolic processes in animals including humans. As the work continues news articles concerning progress can be found abundantly on the World Wide Web....

I've become increasingly suspicious of theories based on DNA analysis.

I agree, especially when they are based on MtDNA alone. (I am not a scientist or anything, just very interested in the subject).

Try this scenario: Neandertal man meets Homo Sapiens woman, recently arrived from Africa. He really likes her legs, finding them to be far more attractive than the short, stocky, Neandertal women's legs. Her skin color is also very exotic. Homo Sapiens woman likes Neandertal man; those huge biceps and forearms, the red hair, and the bulging muscles really turn her on. Neandertal man and Homo Sapiens woman have children.

As I understand it, there would be NO record of Neandertal man in the MtDNA of their offspring. If I am wrong, please correct me. This is one of the largest areas where I have a problem with the Mitochondrial Eve Theory. This is also one reason that I have a problem with the theories that state that the Neandertal is a genetic dead-end, seeing as they are also based on MtDNA. It is strictly a maternal record.

Thanks for your addition.

"I wrote a short paper last year for a Course I took for my own edification."

LOL. Last year for my own edification, I earned a certificate for heating and air conditioning. I sure learned a lot about air conditioning. I was prompted when my AC went out, the AC guy came for 20 minutes and charged me $257.00. I can make minor repairs to my own AC now, and, I know the 'riddle' of all the gasses now. Everyone should be moving toward R-134a, it doesn't contain any HFC's and can be purchased without a license.

I've become increasingly suspicious of theories based on DNA analysis.

I think 'suspicious' is a little too strong, 'cautious' would be the word I'd use.

Dr. Wolpoff, in this apparent 2001 article, seems to be muddying the water by raising doubts about mtDNA to bolster the multi-regional hypothesis that he, along with Alan G. Thorne, helped originate.

While we don't thoroughly understand the workings of DNA and mutations, we've got a pretty good handle on it. So caution would the proper guide when dealing with this data.
In the intervening 5 years there's little evidence that's turned up to support the multi-regionalists, and a great deal that supports Out-of-Africa II hypothesis.

My take on this article is this is 5 year old argument by FUD - Fear Uncertainty Doubt.

Just my opinion of course.

Carleton Coon was the originator of the multiregional hypothesis. There is much to support it...

From a Wolpoff article in Scientific American:

If a worldwide invasion and complete replacement of all native peoples by Eve's descendants actually took place we would expect to find at least some archeological traces of the behaviors that made them successful. Yet examining the archeology of Asia, we can find none. For instance, whereas, the hand axe was a very common artifact in Africa, the technologies of eastern Asia did not include that technology either before or after the Eve peiod.

Just one important fact to muddy the OOA hypothesis...

Carleton Coon was the originator of the multiregional hypothesis. ...

True enough. But his 4/5 lines of H. erectus merging into single H. sapiens sapiens didn't appeal to many. And the (undeserved IMO) charges of racism prompted folks like Gooch and Wolpoff to revise it.

So far the most promising evidence is the remains of 'Portugal boy', showing charateristics of neaderthal and modern saipens. However a sapiens x neanderthal hybrid explains this find better than an erectus x neaderthal off-spring.

For instance, whereas, the hand axe was a very common artifact in Africa, the technologies of eastern Asia did not include that technology either before or after the Eve peiod.

-- Dr. Wolpoff - article in Scientific American

"The Acheulian tradition of tool making spread from Africa into Southwest Asia by 1.4 million years ago and reached southern Europe by at least 600,000 years ago. Until recently, the lack of hand axes at Zhoukoudian and other East Asian Homo erectus sites suggested that the Acheulian tradition did not reach that far. It was thought likely that the same functions that hand axes performed in the west were being performed in the far East by other kinds of tools, perhaps made of bamboo. However, 24 sites in Southern China have now been found to contain Acheulian hand axes dating back about 800,000 years."

-- Early Human Culture - Tool Making

"On December 6, 2005, an opening ceremony for an international symposium on “The Palaeolithic Archaeology in Baise Basin and the Early Human Migrations and Evolutions in the Old Word” was held at Baise City, Guangxi Zhuang Autonomous Region, China. This symposium has invited more than 40 distinguished specialists from Britain, France, United States, German, South Africa, Spain, Israel, India and China.

Since its first discovery in 1973, the Palaeolithic stone tools in Baise, particularly the so-called “Baise handaxe”, have drawn broad attentions from scholars worldwide. Excavations were conducted in the 1980s, followed by multi-disciplinary research projects in the 1990s. Among the challenging academic issues are the early hominids and their cultural features in the Old World, the formation process of red earth in south China, environmental changes, and the living environment of early humans. ..."

-- The Palaeolithic Archaeology in Baise Basin and the Early Human Migrations and Evolutions in the Old Word

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