Too many pairs: DNA, chromatin, and chromosomes

Some facts:

• Molecules of DNA are double-stranded, each strand a perfect complementary copy of the other.
• Humans have 23 pairs of chromosomes.
• Chromosomes are made of DNA.
• We have two copies of each gene.

Where do these two copies of each gene come from — the complementary DNA? Or the pairs of chromosomes? In fact, what is the relationship between DNA and chromosomes? These questions have proven thorny for students in the past, so I'll try here to describe the two different ways in which genetic information is duplicated in a cell.

1. Complementary copies of DNA strands

Molecules of DNA duplicate the information they carry. Each base in a DNA strand is bonded to its complement on the opposite strand: A bonds to T, C bonds to G. It’s like a backup mechanism: if something happens to one part of the strand, the other half is there with the complement of the information. So that’s the first way in which genetic information is paired. And the important part about this pairing is that the pairs are exact complements of each other, like mirror images: the information is duplicated precisely and does not vary.

Part of a DNA strand, demonstrating complementary bases in matching colors

This double-stranded molecule of DNA, then, is wrapped up tightly around proteins called histones, and this set of spools of DNA and histones all together is a material called chromatin.

Chromatin: light blue/green strands of DNA wrapped around bright blue histones.

2. Two copies of each chromosome

Chromosomes are made out of chromatin. In a lot of the pictures of chromosomes in which you can see the chromatin that makes it up, the chromatin looks sort of like yarn woven into a sweater. That’s a reasonable way to think of chromosomes: big structures (big enough that we can see them with a not-too-powerful microscope) made from this yarn-like chromatin.

Cartoon of chromosome made of yarn-like chromatin. (Image by Magnus Manske at Wikipedia.)

 A particular gene is always on a particular chromosome in a given species. For example, the gene for oxytocin, OXT, is always on chromosome 24 in dogs and chromosome 20 in humans. So your chromosomes are very orderly, each one containing a specific set of genes.

Humans have 23 pairs of chromosomes. Dogs have 39 pairs. In fact, Wikipedia has a whole page devoted to the number of pairs of chromosomes in different species. We think of chromosomes as looking like big X. The X is actually the two separate chromosomes in a pair, stuck together during the process of cell division. Usually those two arms of the X are separate in the cell.

Image by JWSchmidt at Wikipedia

In a pair of chromosomes, one chromosome is made of chromatin from one (double) strand of DNA and proteins, which you got from your mother; and the other chromosome is made of chromatin from another (double) strand of DNA and proteins, which you got from your father. So you have, for example, two copies of chromosome 20, one from your mother and one from your father.

Human chromosomes: 23 pairs.

These pairs of chromosomes are the second way in which your genetic information is paired. But this is very different from the exact copy pairing of strands of DNA. Your version of the OXT gene on the chromosome you got from your mother may be slightly different from your version of the OXT gene on the chromosome you got from your father. Where her version had a G-C, his version may have an A-T. (Or it may be just the same.)

DNA differences on two different copies of the same chromosome (see the difference highlighted in blue).

So we have two versions of each gene, one on each chromosome in a matched pair. For a particular gene, we may have two identical copies (in which case we are “homozygous” for that gene) or we may have two different versions (in which case we are “heterozygous” for that gene).

So, yes, we essentially have four instances of each gene in each cell. That’s four instances, but a maximum of two versions of the gene (the doubled instances on a double strand of DNA are always identical complements; it’s only when you compare instances between chromosomes that you may see differences).

In the minds of geneticists, it’s the two versions in the pair of chromosomes which really count. That’s the pair that could differ, after all. And that’s why you'll hear that we have “two” copies of each gene, even though the gene is paired both in the DNA and again between chromosomes.

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Myths in Biology: Mendel's Pea Flowers

At P.Z. Myers' blog, Pharyngula, he has a post on the subject of "myths" in biology, using the number of cell types in humans as an example. He cites Stephen J. Gould's famous article on fox terriers as an example of such myths and how they get incorporated in the science of biology.

You want myths in biology? Pick up any introductory biology textbook and look up Mendel’s original experiments with garden pea plants. Look at the color illustration of the seven phenotypic characters Mendel supposedly tested. Is purple versus white flower color in the figure? Now, read Mendel’s paper describing the seven different characters in garden peas that he studied (you can find the original paper here, in the original German and in English translation). Is purple versus white flower color in the list of characters tested? Interesting…

Toward the end of the paper, Mendel mentions that in a later set of experiments he tested flower color and found the same ratios that he found with the original seven traits he tested. According to the paper, he tested “violett-rothe und weiss Blüthenfarbe” (i.e. “violet-red and white blossom color”), but this test was NOT in his original set of seven experiments, which are the ones always illustrated in biology textbooks.

So, when did biology textbooks start this particular myth? As far as I can tell it was in the first biology textbook with full color illustrations: William T. Keeton’s Biological Science, 2nd ed. The illustrator thought he could kill two birds with one stone by illustrating the technique used to ensure controlled fertilization (i.e. removing the stamens from the flowers using iris scissors) and purple and white flower color. Except that Mendel didn’t study purple versus white flower color in his original series of seven crosses.

Which pair of traits did Mendel actually study, but were replaced by purple versus white flowers in all introductory biology textbooks? The color of the seed-coat, in which gray-brown is dominant and white is recessive. According to Mendel’s original paper, gray-brown seed coats are associated with (what we would now refer to as linked with) “violet-red blossoms and reddish spots in the leaf axils,” but once again Mendel did NOT explicitly test purple versus white flower color in the experiments for which he is remembered, and for which the science of “Mendelian genetics” is named.

And why is the clearly incorrect list (and colored figure) of the seven traits Mendel supposedly studied included in every introductory biology textbook today? Because Keeton’s textbook was the most widely used textbook in biology for decades, so all of the other publishers simply copied what was in his textbook as a way of gaining market share.

Can this myth be corrected now? How many professors’ sets of lecture notes and PowerPoint slides would have to be changed to correct this mistake, and how many textbooks would need new illustrations that included the correct list of the seven traits, and how many people would complain about these changes, or (even worse) suggest that Mendel really did study purple and white flower color in his original series of seven experiments?

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As always, comments, criticisms, and suggestions are warmly welcomed!

--Allen

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Predictions for 2009

Human genomics

The Neanderthal genome will be fully sequenced. There will be no evidence of interbreeding with modern humans (although proponents of the multiregional model will remain unconvinced). By comparing this genome with ours, we may reconstruct the genome of archaic humans who lived almost a million years ago and who were ancestral to Neanderthals and modern humans.

Meanwhile, work will begin on sequencing the genome of early modern humans (10,000 – 40,000 years ago). This project should ultimately prove to be more interesting by showing us how much modern humans have evolved during their relatively short existence. We will probably find out that John Hawks erred on the low side in concluding that natural selection had changed 7% of the human genome over the past 40,000 years.

Darwin remembered

With the 150th anniversary of The Origin of Species, much will appear in 2009 about Charles Darwin and his life. We already know how he came up with his theory of evolution (Darwin salted away almost everything he wrote), although a few questions remain unanswered. What would he have done if he had lived longer? What did he have in mind for future projects?

Probably not much. He had said everything he wanted to say. The Origin of Species (1859) came out of a backlog that had built up in his mind during the previous twenty years. Then came The Descent of Man (1871), which used material left out of The Origin. Finally, The Expression of the Emotions in Man and Animals (1872) was largely a spin-off of The Descent. With this trilogy completed, he had little more to say. A younger Darwin might have addressed one of the dilemmas of evolution. How do selected characteristics perpetuate themselves? What keeps them from being blended away into non-existence with each generation of sexual reproduction? Darwin might have learned about another contemporary scientist, Gregor Mendel, and together the two of them might have proposed a particulate theory of genetics—more than thirty years before later evolutionists rediscovered Mendel’s work. The field of genetics would have developed much faster and, under Darwin’s guidance, may have avoided some of its later blind alleys (e.g., mutation pressure, saltationism, etc.).

Perhaps. But Darwin was unprepared for success. He had finally got to tell the world everything he had so long held back. And the world listened. From then on, a sense of emptiness took over, as if his remaining years were little more than an epilogue.

The Crisis?

The Second Great Depression will not begin in 2009. In any case, what scares me is not the prospect of a sudden drop in the standard of living. Rather, it’s that of a gradual decline to almost half its current value. That scenario is scarier and likelier. And it’s probably already started. For the past fifteen years, median wages have stagnated despite decent economic growth. What will happen when growth stays in the 0-2% range?

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New Definitions of a "Gene"

AUTHOR: RPM

SOURCE: Evolgen

COMMENTARY: Allen MacNeill

RPM at Evolgen has a new post about evolving definitions of a "gene". Here are my thoughts on the subject:

For years I have been teaching my students that a gene is a segment of DNA that codes for a single RNA molecule with a complementary sequence, regardless of whether that RNA molecule is translated or not. This definition takes into account the genes for the various rRNAs and tRNAs, which are not translated, and also other forms of non-translated RNA that have recently been discovered. By this definition, genes that code for mRNAs that are actually translated are distinguished as "structural genes," using terminology that was first developed to describe the Jacob-Monod model of the lactose operon. Using this same terminology, the gene that codes for the lactose repressor protein is a "regulatory gene," insofar as the repressor does not function in an "extrinsic" biochemical pathway, but rather participates in the regulation of other structural genes.

However, the distinction between "structural" and "regulatory" genes outlined above is insufficient to describe the various kinds of genetically significant DNA sequences now known. For example, it does not include regions of the DNA to which protein regulators bind, but which are not themselves transcribed. It also does not distinguish between RNAs that are translated into proteins (either enzymes or repressor/regulator proteins) and those that are transcribed into RNA but never translated (such as rRNA, tRNA, and the newer non-translated RNAs).

Given the foregoing, it appears to me that there are four (possibly five) functionally different kinds of DNA coding sequences:

(1) translatable sequences: those DNA sequences that are both transcribed into mRNA and later translated into proteins, regardless of function (these can be further subdivided into proteins that participate in non-DNA related biochemical pathways and those that directly regulate DNA, but those seem to me to be classifications of the proteins, not the DNA sequences that code for them);

(2) transcribable sequences: those DNA sequences that are transcribed into RNA (i.e. rRNA, tRNA, etc.), but are not later translated into proteins/polypeptide chains. Again, what the RNAs do after being transcribed is not a function of the DNA, but rather of the RNAs, and therefore should not really be used to classify DNA coding sequences;

(3) binding sequences: those DNA sequences that are not transcribed into RNA nor translated into protein, but which function as binding sites for regulatory molecules such as repressor proteins, homeotic gene products, etc. While such sequences do not code for the production of a transcribed or translated gene product, they still participate in the regulation of other genes by serving as regulatory binding sites; and

(4) non-binding sequences: those DNA sequences that are not transcribed into RNA, not translated into protein, nor function as binding sites for regulatory moelcules. Such sequences would include highly repetitive sequences, tandom repeats, "spacer DNA", pseudogenes, retroviral and transposon inserts (both "dead" and potentially "alive"), etc. This latter category could be further subdivided into "functional" non-coding/non-binding DNA sequences versus "non-functional/parastitic" non-coding/non-binding DNA sequences, depending on whether they arise as part of the functional architecture of the DNA (primarily of eukaryotes), or whether they arise as side-effects of the action of parasitic genetic elements, such as retroviruses or transposons.

There may be other categories of DNA sequences that have other functions, but right now I can't think of any. Therefore, this is how I intend to teach the concept of a "gene" to my students at Cornell from now on.

So much for the Beadle/Tatum "one gene, one enzyme" model, eh? And the classical Mendelian definition of "one gene, one phenotypic trait" is no longer viable as well...

--Allen

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