October 20, 2002 | David F. Coppedge

Genes Are Not Telling the Whole Story

A growing realization is dawning on geneticists: there is more going on in DNA than previously imagined.  Now that whole genomes are becoming available, scientists are eagerly trying to understand how the genetic code (genotype) produces a full-grown organism (phenotype), like a fruit fly or human.  The interesting stuff in DNA used to be the genes, but two recent stories are showing that other players in the nucleus may have much more to do with the outcome than just the genes that code for proteins (09/08/2005, 09/23/2005).
(1)  A study from UC San Diego has, once again, showed the functional value of “junk DNA”.  Peter Andolfatto found large differences in non-coding DNA between closely-related species of fruit flies (Drosophila).  These differences appear to be important to the flies, perhaps in maintaining their genetic integrity.  He speculated that these non-coding regions may, therefore, have evolutionary importance.  Andolfatto, who published his findings in Nature,1 explained the change in focus:

Protein evolution has traditionally been emphasized as a key facet of genome evolution and the evolution of new species,” says Andolfatto.  “The degree of protein sequence similarity between humans and chimpanzees, and other closely-related but morphologically distinct taxa, has prompted several researchers to speculate that most adaptive differences between taxa are due to changes in gene regulation and not protein evolution.  My results lend support to this view by demonstrating that regulatory changes have been of great importance in the evolution of new Drosophila species.”   (Emphasis added in all quotes.)

Andolfatto et al. found that about 50% of the non-coding DNA appeared to be under negative selection (i.e., evolutionary conservation), and other parts appeared to be under positive selection (although determining this is a statistical comparison of nucleotide substitutions to polymorphisms, not a linking of variations to actual fitness benefits).  This appears to be a “double whammy” against Kimura’s neutral theory of evolution, said Alexey S. Kondrashov, in the same issue of Nature,2 who said about this study, “Fruitfly genome is not junk.”  He began his analysis with a fairy tale that has been debunked:

Once upon a time, the world seemed simple when viewed through the eyes of evolutionary biologists.  All genomes were tightly controlled by various forms of natural selection.  DNA encoded functional genes, and most mutations that occurred were rejected through negative selection.  Those exceptional mutations that were beneficial substituted for the original gene variant (allele) and spread through the evolving populations by positive selection.  And polymorphisms – where several alleles coexist within a population – were maintained by yet another, balancing, form of selection.

Though Kondrashov is not ready to conclude that higher vertebrates are lacking in junk DNA and neutral mutations, or that Kimura’s neutral theory has been debunked outside of fruit flies, he draws one important conclusion from the new study: “It is truly amazing how little we know quantitatively about mutation and selection in the genomes of even the most well-studied organisms.”  See also Science Daily summary of this story.
(2) A separate study – closer to us humans – also found a big surprise in our DNA.  Ten years ago researchers were talking about “the human genome” as if there were a commonly-shared genetic code among us all.  While that is still largely true, scientists have been stunned by the amount of individual variation.  Erika Check, writing in Nature,3 explained:

Exactly one year ago this week, scientists announced that they had finished the ‘Book of Life’.  The complete sequence of the human genome had been painstakingly reduced to an ordered list of letters representing the four bases of DNA.  This text was believed to be virtually identical for every person on Earth – and the major differences between individuals, such as hair colour, were said to be the equivalent of typographical errors, no longer than a single letter.  The next major task for scientists was to find out which of these tiny differences can cause disease.
    But even as the ink was drying on the complete sequence, some researchers were questioning whether there was really such a thing as the definitive edition of the Book of Life.  By skim-reading individual genomes, these scientists were finding bizarre and unexpected irregularities.  In some people, whole paragraphs of the text were duplicated, whereas in others, large passages were missing, or even printed backwards.  These major revisions turned up in all kinds of people, including many who seemed healthy and normal.  Suddenly, it seemed possible that there was actually no standard version of the Book of Life, and researchers wondered whether we are all much more different from each other than they had thought.

These discoveries of major individual genetic differences, which began to surface in 2002 and 2003, have grown.  Scientists were “freaked out” to find different numbers of copies of genes in different people, and then to find whole sections missing or written backwards in normal-looking people was almost unbelievable.  So far these seem to affect 3.5% of the genome – a bigger portion than the oft-alleged differences between humans and chimpanzees.  (Those differences have grown, also, in the realization that non-coding elements and regulatory processes play a much more significant role than previously thought.)  Some of the differences may be matters of life or death – susceptibility to disease, or ability to adapt to certain environments, but many of them seem to provide no obvious phenotypic advantage or disadvantage, and all humans are clearly interfertile still.  What all this means is a matter of intense debate.  Erika Check concludes, “For now, the realization that we are all reading from individual texts has already altered scientists’ understanding of humanity – and of the library of unique volumes that makes up the human race.”

1Peter Andolfatto, “Adaptive evolution of non-coding DNA in Drosophila,” Nature 437, 1149-1152 (20 October 2005) | doi: 10.1038/nature04107.
2Alexey S. Kondrashov, “Evolutionary biology: Fruitfly genome is not junk,” Nature 437, 1106 (20 October 2005) | doi: 10.1038/4371106a.
3Erika Check, “Human genome: Patchwork people,” Nature 437, 1084-1086 (20 October 2005) | doi: 10.1038/4371084a.

Neo-Darwinism was built on a pre-genomic, simplistic view of inheritance.  It, and its successors, can no longer pretend to account for the new complexities of genetics that are coming to light.
    More recently, evolutionists have attempted to arrange organisms into phylogenetic trees based on sequence similarities of this or that gene.  This is like focusing on individual trees and missing the forest.  There is much more than just genes and their protein products accounting for our individual differences.  If the genes are just pawns of regulatory processes, who is regulating the regulators?  How does a mature individual arise from the complex sequence of developmental processes that know which genes to switch on at the right times?
    In times of intellectual ferment such as this, it is unfair to grant sole authority for explanations to one team, the Darwin Bulldogs, that has repeatedly struck out.  Manager Charlie would never have predicted the curve balls that the nature would pitch at them.  Bluffing confidence and armchair strategies have proven inadequate.  Let design science come to bat.

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Categories: Genetics, Human Body

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