Today’s New Reason To Believe

Posted by Fazale ‘Fuz’ Rana, Ph.D.

Human DNA Contamination Explains Away Genetic Evidence for Human-Neanderthal Interbreeding

You love her
She loves him
He loves somebody else
You just can’t win

-J. Geils Band, Love Stinks

My father had his share of idiosyncrasies. Even though he was a no-nonsense guy, he loved soap operas.

My dad was a nuclear physicist and a college professor. When I was a little kid, we lived on the campus of West Virginia Institute of Technology, where my father taught and served as the chairman of the physics department. He was well-known for instilling fear in the hearts of engineering students who took his classes. Yet, I remember him coming home every day at 2:00 p.m. for an hour to watch Days of Our Lives. He was totally caught up in the make-believe lives of the characters that resided in Salem.

It’s easy to get hooked on the intrigue of a soap opera, no matter how educated and sophisticated you are. I have been closely following a soap opera, of sorts, myself. Instead of being aired on network TV, this drama has unfolded in the pages of the scientific literature. Did Neanderthals and modern humans interbreed? I can hardly wait for the next episode of scientific discoveries to find out.

To date the wait has been well worth it. True to form for a good soap opera, a new study published in PLoS Genetics adds an interesting plot twist to the story.

Until this most recent work, it appeared that Neanderthals and humans had an on-again, off-again romance. Some studies suggest that the two creatures interbred; others indicate that they had nothing to do with each other.

The primary evidence for interbreeding between humans and Neanderthals comes from the fossil record. (See here, here, and here.) Though controversial, a few hominid finds appear to possess a mosaic of human and Neanderthal features, leading to the conclusion that they were Neanderthal-human hybrids. There is also some indirect genetic evidence for interbreeding as well.

On the other hand, analysis of mitochondrial DNA isolated from Neanderthals provides direct evidence that these two species did not hook up.

Preliminary results from studies of Neanderthal nuclear DNA have been much less clear cut, however (Science, November 16, 2007, p. 1068-1071). Analysis of nuclear DNA is potentially much more informative than mitochondrial DNA. One analysis of Neanderthal nuclear DNA sequences, conducted by a team from the Joint Genome Institute in the US, found no evidence for interbreeding. Another analysis, performed by researchers from the Max Plank Institute in Germany, however, noted some human genetic signatures in the Neanderthal genome, indicating that humans contributed to the Neanderthal gene pool.

To help understand why these two studies yielded disparate results, a team from the University of California, San Francisco, reanalyzed data from both studies. In principle, these two studies should have produced the same result, since both research teams were working with the same samples taken from a single Neanderthal specimen.

Reevaluation of the data from the two studies indicates that one of the research teams—the one that detected interbreeding—inadvertently introduced human DNA as a contaminant into the Neanderthal DNA, explaining why it appears that humans interbred with these hominids.

Alas, in a somewhat anticlimactic fashion, the sordid affair between Neanderthals and humans comes to an end. The scientific evidence increasingly indicates that Neanderthals and humans had nothing to do with one another.

We were friends
But now it’s the end of our love song…

-Dave Mason, We Just Disagree

For more on the relationship between humans and Neanderthals see Who Was Adam?

Junk DNA Plays an Important Role in Development

My wife enjoys looking for antiques (and, to my horror, buying them.) For Amy, antiques are priceless treasures. From my standpoint, these relics from the past are just old junk.

For a number of years, biochemists thought that a vast proportion of the genomes of most organisms consisted of old junk—DNA sequences that once had value, but were transformed into nonfunctional elements.

Evolutionary biologists consider the existence of “junk” DNA as one of the most potent pieces of evidence for biological evolution. According to this view, junk DNA results when undirected biochemical processes and random chemical and physical events transform a functional DNA segment into a useless molecular artifact. Junk pieces of DNA remain part of an organism’s genome solely because of its attachment to functional DNA. In this way, junk DNA persists from generation to generation.

Evolutionists also highlight the fact that in many instances identical (or nearly identical) segments of junk DNA appear in a wide range of related organisms. Frequently the identical junk DNA segments reside in corresponding locations in these genomes. For evolutionists, this clearly indicates that these organisms shared a common ancestor. Accordingly, the junk DNA segment arose prior to the time that the organisms diverged from their shared evolutionary ancestor. Evolutionists ask, “Why would a Creator purposely introduce nonfunctional, junk DNA at the exact location in the genomes of different, but seemingly related, organisms?”

Recent studies on junk DNA provide a response to this question—one that evolutionists find surprising, yet hard to deny. Junk DNA possesses function. (For a detailed discussion of some of these discoveries see Who Was Adam?

New work by scientists from Stanford University and the University of California, Santa Cruz on transposable elements provides added insight into the functional range of junk DNA.

Transposable elements (TE) are mobile pieces of DNA that have highly repetitive sequences. TEs duplicate themselves and then randomly insert into the genome, presumably creating junk DNA along the way.

Biochemists have noted, however, that when compared across organisms, the sequences of many TEs are nearly identical or conserved. Biochemists consider sequence conservation an indicator of function. To say it another way, TEs are not junk. If a DNA sequence is functional, any change to the sequence as a result of a mutation would potentially render it nonfunctional. In principle, lost function would compromise the fitness of the organism. And natural selection would weed it out of the population, conserving the DNA sequence.

Like my wife in an antique mall, the researchers from Stanford and UC, Santa Cruz surveyed 10,402 sequences in the human genome to gain better understanding of the function of TEs. It turns out that TEs control the activity of transcription factors. These proteins regulate gene expression. TEs also control developmental genes. These genes regulate the developmental process as organisms transform from an embryo into an adult form.

Interestingly, many of the functional TEs reside in gene deserts, vast regions in the genome devoid of genes. Based on this new research, it looks as if these genetic wastelands are replete with functional oases. In fact, one of the researchers noted that gene deserts are better described as “regulatory jungles.”

The recognition that junk DNA has function weakens the best argument for biological evolution and common descent. It also explains why identical junk DNA sequences occur in corresponding regions of the genomes of related organisms. The precise location of TEs is critical for these sequences to properly regulate gene activity.

Junk DNA appears to be a valuable antique reflecting the enduring design of a Divine Craftsman, and not a trinket destined for the trash.

DNA Researchers Uncover Evidence that Overlapping Genes Are Widespread in Mammal Genomes

I have never cared much for puzzles, but I know some people can’t get enough of them. (Although admittedly, I’ve gotten hooked on Sudoku.)

Whether you are a fan of the Sunday Puzzle or not, I have a word challenge for you. This game illustrates the concept of overlapping genes and hopefully will help you appreciate why I think biochemical systems represent the most profound evidence for intelligent design.

The Challenge

The rules for this game are straightforward. Come up with a sentence (or even a word) that will yield another meaningful sentence (or word) if the reading frame is shifted by either one or two letters to the right or left. For example:

Original sentence:

    The boy went to the store.

Reading frame shifted by one letter to the left:

    T heb oyw entt ot hes tore.

Reading frame shifted by two letters:

    Th ebo ywe ntto th est ore.

I have yet to come up with a sentence that works. Yet, solutions to this type of puzzle abound in the genomes of a wide range of organisms in the form of overlapping genes.

A Biochemistry Primer

Genes are segments of DNA that house the information the cell’s machinery uses to manufacture proteins.

Genes consist of a sequence of nucleotides (or genetic letters), abbreviated A, G, C, and T, linked together to form a molecular chain. The specific sequence of nucleotides dictates the amino acid sequence of the protein encoded by a particular gene.

The cell’s machinery builds proteins using twenty different amino acids. The specific amino acid sequence determines the way the protein chain folds into a complex and precise three-dimensional structure. The overall shape of the protein dictates its function.

The set of rules the cell’s machinery uses to relate the nucleotide sequence of a gene to the amino acid sequence of a protein is called the genetic code. The fundamental unit in the genetic code is a sequence of three nucleotides, referred to as a codon. There are sixty-four codons in the genetic code, since there are four different nucleotides found in DNA (4 ³ =64). The coding assignments of the genetic code are redundant in some cases, since sixty-four codons specify twenty amino acids. Some amino acids are signified by a single codon only. Other amino acids are connoted by several different codons.

To illustrate how the genetic code translates information stored in DNA into information functionally expressed by proteins, consider the short messenger RNA nucleotide sequence: UCU CCU GCA AUU CGU AU. (To make proteins, the cell’s machinery first copies the information housed in the gene by assembling a chain-like molecule called messenger RNA [mRNA]. Like DNA, mRNA consists of a sequence of nucleotides. The cell’s machinery uses the same nucleotides to make mRNA as DNA with one exception: U is used in place of a T.)

    Position:   123
                UCU CCU GCA AUU CGU AU

If the cell’s biochemical apparatus uses a reading frame that begins at the first position, the resulting protein will have the sequence: serine-proline-alanine-isoleucine-arginine, since UCU signifies serine, CCU signifies proline, etc. If the reading frame starts at the second position in the nucleotide sequence, an entirely different protein will be generated with the sequence: leucine-leucine-glutamine-phenylalanine-valine. Shifting the reading frame to the third nucleotide position yields a peptide with the sequence: serine-cysteine-asparagine-serine-tyrosine.

As evinced by this example, there are only three possible reading frames for a nucleotide sequence. Three very different proteins can be encoded by a single nucleotide sequence, simply by shifting the reading frame by either 1 or 2 nucleotides.

Biochemists believe that in most cases only one reading frame is used in living systems, and the nonoverlapping, “one gene, one protein” relationship holds. This expectation stems from repeated observations that when a gene’s reading frame shifts as a result of a mutation, it almost always leads to catastrophic results. These so-called frameshift mutations result when nucleotides are accidentally inserted or deleted from a gene. And, as made evident in the above example with the model nucleotide sequence, a frameshift produces a protein with a radically different amino acid sequence. The mutant protein almost always is nonfunctional junk.

Frameshift mutations stand in contrast to substitution mutations, which involve the replacement of one nucleotide with another. This type of mutation merely replaces the one amino acid in the polypeptide chain with another. All other amino acids remain unchanged. Substitution mutations can be catastrophic, but more often than not these types of errors have limited, if any, effect on protein function because the gene’s reading frame hasn’t changed.

Overlapping Genes

But in some cases two reading frames are used, and two genes overlap onto the same nucleotide sequence. In the late 1970s biochemists studying the bacteriophage fX174 (a virus that infects the bacterium, Escherichia coli) made a startling discovery: the genome of this bacteriophage directs the production of more proteins than it should, based on the size of its DNA. Researchers resolved this paradox when they demonstrated that some of the fX174 genes overlap (for example, see Nature 264 1976: 34-41).

This conclusion was quite unsettling at that time. Biochemists had considered the relationship “one gene, one protein” to be absolute and a cornerstone of molecular biology. Since the work on the bacteriophage fX174 genome biochemists have identified overlapping genes in other viruses, as well as in bacteria, insects, fish, and mammals. In each case, overlapping genes are read by the cell’s machinery using a different reading frame.

Researchers noted that in most cases overlapping genes occur in some of the smallest, most compact genomes in nature (viruses and parasitic bacteria, like Mycoplasma genitalium.) The prevailing thinking was that the occurrence of overlapping genes in more-complex creatures was a rarity because they represent a costly arrangement for the organism. Mutations to one gene also mutate the overlapping partner.

A new study challenges this biochemical orthodoxy. A team of American and European scientists uncovered evidence that overlapping genes may well be widespread in mammal genomes. They point out that:

the skepticism surrounding eukaryotic dual coding is unwarranted: rather than being artifacts, overlapping reading frames are often hallmarks of fascinating biology.

This study provides motivation for molecular biologists to search for more examples of overlapping genes in mammals and other complex organisms. The new expectation is that more and more examples will be found.

The apparent widespread occurrence of overlapping genes doesn’t make much sense from an evolutionary perspective, because of the cost they represent to the organism. This cost is only worth it if there is a rationale for overlapping genes. The research team notes that the overlapping genes they uncovered seem to be involved in biochemical multitasking.

Even though it is not a direct analogy to the overlapping genes found in the genome of organisms, the “overlapping sentence” word challenge highlights how difficult it is to come up with a sequence of letters (or in biochemical systems: nucleotides and amino acids) that house overlapping messages, even when an intelligent agent diligently seeks out a solution. Yet, solutions to this biochemical conundrum seem to abound throughout nature. For me, the only explanation for overlapping genes is the work of a Creator. It’s hard to imagine how undirected evolutionary processes could produce overlapping genes.

For more reasons why biochemical information points to the work of a Creator, see Fazale Rana, “FYI: ID in DNA,” Facts for Faith (issue 8, 2002).