Going beyond the gene

kw: book reviews, nonfiction, genetics, epigenetics, twin studies

You meet a pair of identical twins. They seem really, really identical: they may be dressed the same, they have the same mannerisms, hair style, voice and speech pattern, and so forth. Give it time. Over many experiences you'll learn to tell them apart. One has a mole on the cheek the other doesn't have, or they like different bands or kinds of music or subjects at school. The time will come that you wonder why you ever confused them.

They are a lot alike, truly. But why aren't they more identical? Identical twins arise when a single egg, or an embryo at a very early stage, splits in half. The two individuals that are born are thus a clone (did you know "clone" is a collective noun?)—their genetics are identical. Now, in their lifetimes, each will pick up random mutations, and as many as 100 of these will affect their sex cells and be passed on to their offspring. That's two or three heritable mutations per year of life. Such a mutation may explain the mole on one cheek. But some differences that occur cannot be so simply explained. Are they purely due to random environmental differences (this is the nurture hypothesis)?

Tim Spector researches twins. In his book Identically Different: Why We Can Change Our Genes, he discusses many interesting cases that show just how different the members of a twin clone can be, in spite of having "exactly the same genes." I have a quibble about the book's subtitle. In one way, it is quite accurate, but in another it is very misleading. That is, this is a book about epigenetics, and the mechanisms of epigenetics do make changes to genes, and such changes are often heritable. However, the ACGT sequences are not changed, and epigenetic changes are reversible. A more accurate (but clumsier) subtitle would be Why We Can Change Which of Our Genes are Used.

In all the hoopla surrounding the completion of the Human Genome Project a decade ago, it was not mentioned that we knew nothing about why cells differentiated into tissues. Every cell in your body has the same DNA, the same genes. What makes the cells in the cornea of the eye transparent and silent, while muscle cells are dark brownish red and can quickly change shape? The difference is in which portions of DNA, that is, which genes (and, it is quite certain, which sections of "noncoding DNA" that some folks used to call "junk DNA") are actually used and which are not, by that cell. Tissues differentiate by epigenetically silencing many genes.

Two mechanisms make temporary modifications to DNA to prevent or allow certain genes to operate: methylation and histone modification. Look them up for more detail. In short, methylation can happen quickly, as can demethylation. In methylation a number of -CH3 groups are attached to a section of DNA, which jams the DNA-to-RNA copying mechanism so that gene is not expressed (i.e., not used). In demethylation, they are removed and the gene is active again. In histone modification, larger chemical groups get attached to the "spool" proteins that help DNA wind up so it will fit in the cell nucleus. Some modifications slow down the unspooling needed so the gene can be used, or stop it entirely. This is a slower process. But both kinds of modifications can last a long time, and both kinds can affect sex cells and be passed on to offspring. That means that some changes in DNA expression that occur in your lifetime can be inherited by your children.

This means that Larmarck was partly right! He is widely lampooned for having a "wrong" hypothesis for evolution. Yet we find he was not entirely wrong. In one "natural experiment" described in the book, some of the Dutch people were systematically starved during World War II, during a period of a few months. During that time and for some months afterward, babies were born. Babies of starving mothers were small and grew up smaller than ordinary. What is of interest here is, their own children were also smaller. The effect could be traced several generations in some families. Epigenetic changes that occurred during development in the womb affected the size of children and grandchildren, taking 3-4 generations to be reversed.

In areas that two twins are quite ordinary, they are likely to be very similar. In other areas, not so. For example, a number of twins are discussed in which one member is homosexual and the other is not. In some of these cases, the non-gay twin had tried out homo-sex and didn't like it, and remained heterosexual thereafter. The author considers that the tendency to be attracted to one's own sex is under genetic influence, but that a minor epigenetic difference can push a person one way or the other, in how they are going to live as a result. It is well known that in a prison situation about half of male inmates practice homo-sex (not always so willingly), but there is the other half that do not, and apparently put up sufficient resistance when pressed to avoid it altogether. Most of the half who do so practice, never do "on the outside". They prefer female partners, and resort to male partners only when that's all that is available.

Among "identical" twins, then, there is surprising variability. Sometimes they have different eye colors, more frequently they pursue different careers and may seek out different kinds of marriage partners. One may be musical and the other not. In a late chapter, the author discusses an apparent tendency in nature to maximize diversity. It is a kind of hedge against an uncertain future. This is seen in inbred laboratory mice. They have been inbred on purpose, so as to be a near-clone with many members. Yet in any litter, their personalities differ: one is the boldest, another the shyest, and others more or less active or greedy when eating. Natural epigenetic changes seem to assure that as conditions change, one or a few will be better able to take advantage, or to survive.

Now, can we really, on purpose, make epigenetic changes that will affect our children? One way is to make a radical change in your habits of eating and exercise. If you boost your exercise a great deal, your kids may not be a great deal more muscular, but they might find it easier to "get muscles". For more subtle matters, drug companies are very interested in compounds that will promote either methylation or demethylation of target genes that affect the outcome of a disease or birth defect. It may even be possible to modify our alimentary flora (the bacteria that live inside us, some 10 to 100 trillion of them). The internal flora of a slender person differ from those of an obese person. One doctor is experimenting with "fecal transplants" (an enema of the germs from someone else's bowel), which have cured some people of irritable bowel syndrome, and may be able to change how efficiently food is used. That could make a dent in someone's obesity, if their digestion became much less efficient! It is hard to say at this point, though, if this is an epigenetic change, or if having a different internal population just makes things work differently without epigenetics being involved.

The book is a portent of future things. There may one day be ways to tinker with our epigenetics to make us healthier and happier. Just how much of this we want to take advantage of, is anyone's guess. What seems strange or even threatening to this generation will be commonplace to the next.