Was natural selection at work?

RIVERSIDE, Calif. (www.ucr.edu) -- A team of biochemists from UC Riverside published a paper in the June 11 issue of the Journal of Molecular Biology that gives one explanation for why humans and primates are so closely related genetically, but so clearly different biologically and intellectually.

It is an established fact that 98 percent of the DNA, or the code of life, is exactly the same between humans and chimpanzees. So the key to what it means to be human resides in that other 2 percent.

According to Achilles Dugaiczyk, professor of Biochemistry at UCR, one important factor resides in something called Alu DNA repeats, sometimes called "junk DNA." These little understood sections of DNA are volatile, and prone to sudden mutations, or genomic rearrangements. At times the results are beneficial in that they give rise to new proteins or an altered gene regulation. Sometimes the mutations result in the growth of a cancer tumor, or some other genetic defect.

The team, which also included Rosaleen Gibbons, Lars J. Dugaiczyk, Thomas Girke, Brian Duistermars and Rita Zielinski, identified over 2,200 new human specific Alu DNA repeats that are absent from the chimpanzee and most likely other primates.

"The explosive expansion of the DNA repeats and the resulting restructuring of our genetic code may be the clue to what makes us human," Dugaiczyk said. “During the same amount of time, humans accumulated more genetic novelties than chimpanzees, making the human/chimpanzee genetic distance larger than that between the chimpanzee and gorilla.”

Metaphorically speaking, Dugaiczyk said, “Humans and primates march to the rhythm of a drum that looks identical; the same size, shape and sound. But, the human drum beats faster.”

This chemical analysis of DNA structures also showed something else. The spread of the Alu DNA repeats was written into the chemistry of human chromosomes. The process was not random, Dugaiczyk said, and it was not subject to an environmental "natural selection," separating winners and losers as theorized by Darwin.

I question Dugaiczyk's assertion that the spread of Alu repeats was not selected for. Perhaps each repeat's appearance was not selected for. But possibly a mechanism that increased the rate at which Alu repeats accumulated was selected for. Another possibility is that they were selected for in order to move genes around to make certain genes easier to get to for transcription. If the ancestors of humans were under heavier selective pressure once they broke off from chimps then that may have selected for more large scale rearrangements of the 3-D shape of chromosomes in order to allow changes in frequencies of expression of various genes.

Perhaps what the meaning that Dugaiczyk is trying getting to across is being lost by the short length of the press release. Does he think these Alu repeats are having no effect on phenotype and that they represent a spreading of parasitical DNA sequences? It is not clear.

"We are not contending that natural selection does not exist, but that in this instance it is a chemical process within human chromosomes that explains why humans have an explosive expansion of DNA repeats, and primates do not," Dugaiczyk said.

A chemical process? Mediated by enzymes perhaps? What caused those enzymes to start causing more Alu repeats? Did a genetic mutation make Alu repeats more likely to be generated in the germ line? Or did humans come under other selective pressures that by accident were at odds with selecting against accumulation of junk repeat sequences?

Determining the genetic differences between humans and primates is important for several reasons, Dugaiczyk said, including advancing knowledge about how life developed and evolved on earth. Other benefits include making it easier to identifying human predisposition to genetic disease, by comparing humans with other primate species. A third possible benefit is to underline the importance of protecting endangered primate species.

Another advantage to doing comparisons of genetic differences both between and within species is that we can discover the advantages and disadvantages of each variation for the purpose of future genetic engineering. Replace some of one's own parts with better parts. Or create offspring with a collection of advantages that no single human possesses today.

I question whether we really know enough about how many genetic differences there are between species or which ones are most important. Just within the human species the recent discovery of lots of large copy variations (LCVs) effectively more than doubled the previous estimate of how many genetic variations there are between individual humans.

TORONTO -- Scientists at The Hospital for Sick Children (Sick Kids), Brigham and Women's Hospital (BWH) and Harvard Medical School (HMS) have made the unexpected discovery that significant differences can exist in the overall content of DNA and genes contained in individual genomes. These findings, which point to possible new explanations for individual uniqueness as well as why disease develops, are published in the September 2004 issue of the scientific journal Nature Genetics (available online August 1, 2004).

"Using new genome scanning technologies, we serendipitously found stretches of DNA sometimes hundreds of thousands of chemical bases (nucleotides) long that were present or absent in the genomes of healthy individuals. These large-scale copy variations, or LCVs, frequently overlap with genes and could explain why people are different," said Dr. Stephen Scherer, co-principal investigator of the study, a Sick Kids senior scientist, and an associate professor in the Department of Molecular and Medical Genetics at the University of Toronto.

"At first we were astonished and didn't believe our results because for years we had been taught that most variation in DNA was limited to very small changes. Then we heard the Harvard group was making similar observations and ultimately we combined our data and came to the same conclusion," added Dr. Scherer.

Early information from the Human Genome Project indicated that the DNA in the genome of any two individuals is 99.9 per cent identical with the 0.1 per cent variation arising primarily from some three million single nucleotide changes scattered amongst the chromosomes. The new data from the Sick Kids and Harvard groups revealed 255 regions (comprising more than 0.1 per cent) of the genome where large chunks of DNA are present in different copy numbers between individuals. Over 50 per cent of these alterations lead to changes in gene numbers and at least 14 regions overlapped with known sites associated with human disease.

Since discoveries of genetic differences between humans of this order of magnitude are being found at this stage in the game any estimates about which genetic variations are most responsible for making us different from other primates should be seen as tentative guesses at this point. Those estimates may be based on false assumptions about how many and what kinds of genetic variations any two species have. There may be yet more genetic variations waiting to be discovered and some of the regions now thought to contain junk DNA may be serving some as-yet-undiscovered regulatory purposes.

For more on the significance of the LCV discovery see Godless Capitalist's coverage as well as The Personal Genome's coverage.