The Ash Twins Blog

The NYTimes has two worthwhile articles about genetics on two consecutive days. The first, “The Rest of the Genome,” discusses non-DNA inheritance:

…several different proteins may be produced from a single stretch of DNA. Most of the molecules produced from DNA may not even be proteins, but another chemical known as RNA. The familiar double helix of DNA no longer has a monopoly on heredity. Other molecules clinging to DNA can produce striking differences between two organisms with the same genes. And those molecules can be inherited along with DNA…

Scientists discovered that when a cell produces an RNA transcript, it cuts out huge chunks and saves only a few small remnants. (The parts of DNA that the cell copies are called exons; the parts cast aside are introns.) Vast stretches of noncoding DNA also lie between these protein-coding regions. The 21,000 protein-coding genes in the human genome make up just 1.2 percent of that genome.

One of the biggest of these projects is an effort called the Encyclopedia of DNA Elements, or Encode for short. Hundreds of scientists are carrying out a coordinated set of experiments to determine the function of every piece of DNA in the human genome…

Encode’s results reveal the genome to be full of genes that are deeply weird, at least by the traditional standard of what a gene is supposed to be…

A single so-called gene, for example, can make more than one protein. In a process known as alternative splicing, a cell can select different combinations of exons to make different transcripts… Several studies now show that almost all genes are being spliced. The Encode team estimates that the average protein-coding region produces 5.7 different transcripts. Different kinds of cells appear to produce different transcripts from the same gene.

Even weirder, cells often toss exons into transcripts from other genes. Those exons may come from distant locations, even from different chromosomes…

…the genome is also organized in another way, one that brings into question how important genes are in heredity. Our DNA is studded with millions of proteins and other molecules, which determine which genes can produce transcripts and which cannot. New cells inherit those molecules along with DNA. In other words, heredity can flow through a second channel…

All of the molecules that hang onto DNA, collectively known as epigenetic marks, are essential for cells to take their final form in the body. As an embryo matures, epigenetic marks in different cells are altered, and as a result they develop into different tissues. Once the final pattern of epigenetic marks is laid down, it clings stubbornly to cells. When cells divide, their descendants carry the same set of marks…

When an embryo begins to develop, the epigenetic marks that have accumulated on both parents’ DNA are stripped away. The cells add a fresh set of epigenetic marks in the same pattern that its parents had when they were embryos.

This process turns out to be very delicate. If an embryo experiences certain kinds of stress, it may fail to lay down the right epigenetic marks.

In 1944, for example, the Netherlands suffered a brutal famine. Scientists at the University of Leiden recently studied 60 people who were conceived during that time. In October, the researchers reported that today they still have fewer epigenetic marks than their siblings. They suggest that during the 1944 famine, pregnant mothers could not supply their children with the raw ingredients for epigenetic marks…

… Matthew Amway of Washington State University and his colleagues found that exposing pregnant rats to a chemical for killing fungus disrupted the epigenetic marks in the sperm of male embryos. The embryos developed into adult rats that suffered from defective sperm and other disorders, like cancer. The males passed down their altered epigenetic marks to their own offspring, which passed them down to yet another generation.

Last year Dr. Amway and his colleagues documented an even more surprising effect of the chemical. Female rats exposed in the womb avoided mating with exposed male rats. The scientists found this preference lasted at least three generations…

…RNA guides, like the RNA molecules in ribosomes, do not fit the classical concept of the gene. Instead of giving rise to a protein, these RNA molecules immediately start to carry out their own task in the cell…

Although only 1.2 percent of the human genome encodes proteins, the Encode scientists estimate that a staggering 93 percent of the genome produces RNA transcripts…

Only about 4 percent of the noncoding DNA in the human genome shows signs of having experienced strong natural selection. Some of those segments may encode RNA molecules that have an important job in the cell. Some of them may contain stretches of DNA that control neighboring genes. Dr. Haussler suspects that most of the rest serve no function.

“Most of it is baggage being dragged along,” he said…

Mutations can make it impossible for a cell to make a protein from a gene. Scientists refer to such a disabled piece of DNA as a pseudogene. Dr. Gerstein and his colleagues estimate that there are 10,000 to 20,000 pseudogenes in the human genome. Most of them are effectively dead, but a few of them may still make RNA molecules that serve an important function. Dr. Gerstein nicknames these functioning pseudogenes “the undead.”…

Much of the baggage in the genome comes not from dead genes, however, but from invading viruses. Viruses repeatedly infected our distant ancestors, adding their DNA to the genetic material passed down from generation to generation. Once these viruses invaded our genomes, they sometimes made new copies of themselves, and the copies were pasted in other spots in the genome. Over many generations, they mutated and lost their ability to move.

“Our genome is littered with the rotting carcasses of these little viruses that have made their home in our genome for millions of years,” Dr. Haussler said…

Yet some of these invaders have evolved into useful forms. Some stretches of virus DNA have evolved to make RNA genes that our cells use. Other stretches have evolved into sites where our proteins can attach and switch on nearby genes. “They provide the raw material for innovation,” Dr. Haussler said.

The second piece, “In a Novel Theory of Mental Disorders, Parents’ Genes Are in Competition,” presents an innovative theory of autistic and schizophrenic symptoms:

Their idea is, in broad outline, straightforward. Dr. Crespi and Dr. Badcock propose that an evolutionary tug of war between genes from the father’s sperm and the mother’s egg can, in effect, tip brain development in one of two ways. A strong bias toward the father pushes a developing brain along the autistic spectrum, toward a fascination with objects, patterns, mechanical systems, at the expense of social development. A bias toward the mother moves the growing brain along what the researchers call the psychotic spectrum, toward hypersensitivity to mood, their own and others’. This, according to the theory, increases a child’s risk of developing schizophrenia later on, as well as mood problems like bipolar disorder and depression.

The idea of inter-gene competition is familiar to geneticists, but identifying autism solely with the sperm and schizophrenia solely with the egg struck me as totally implausible. The article later presents the following as evidentiary support for the theory:

Those with the genetic disorder called Angelman, or “happy puppet,” syndrome practically dance through the day, have difficulty communicating and are demanding of caregivers. Those born with a genetic problem known as Prader-Willi syndrome are placid, compliant and as youngsters low maintenance.

Yet these two disorders, which turn up in about one of 10,000 newborns, stem from disruptions of the same genetic region on chromosome 15. If the father’s genes dominate in this location, the child develops Angelman syndrome; if the mother’s do, the result is Prader-Willi syndrome, as Dr. Haig and others have noted. The former is associated with autism, and the latter with mood problems and psychosis — just as the new theory predicts.

I am skeptical of this apparent correlation between which parent’s genes “dominate” and autistic/schizophrenic symptoms. It is unclear from the article whether this means dominance/recessiveness or something else. It might make sense on some intuitive folk-psychology level, but it is just wholly implausible to infer this mechanism from the intuition that autistm is maleness and schizophrenia is femaleness.