What is a gene?

Now: The Rest of the Genome
by Carl Zimmer

In this jungle of invading viruses, undead pseudogenes, shuffled exons and epigenetic marks, can the classical concept of the gene survive? It is an open question, one that Dr. Prohaska hopes to address at a meeting she is organizing at the Santa Fe Institute in New Mexico next March.

In the current issue of American Scientist, Dr. Gerstein and his former graduate student Michael Seringhaus argue that in order to define a gene, scientists must start with the RNA transcript and trace it back to the DNA. Whatever exons are used to make that transcript would constitute a gene. Dr. Prohaska argues that a gene should be the smallest unit underlying inherited traits. It may include not just a collection of exons, but the epigenetic marks on them that are inherited as well.

These new concepts are moving the gene away from a physical snippet of DNA and back to a more abstract definition. “It’s almost a recapture of what the term was originally meant to convey,” Dr. Gingeras said.

A hundred years after it was born, the gene is coming home.

Genome 2.0: Mountains Of New Data Are Challenging Old Views
by Patrick Barry

This complex interweaving of genes, transcripts, and regulation makes the net effect of a single mutation on an organism much more difficult to predict, Gingeras says.

More fundamentally, it muddies scientists’ conception of just what constitutes a gene. In the established definition, a gene is a discrete region of DNA that produces a single, identifiable protein in a cell. But the functioning of a protein often depends on a host of RNAs that control its activity. If a stretch of DNA known to be a protein-coding gene also produces regulatory RNAs essential for several other genes, is it somehow a part of all those other genes as well?

To make things even messier, the genetic code for a protein can be scattered far and wide around the genome. The ENCODE project revealed that about 90 percent of protein-coding genes possessed previously unknown coding fragments that were located far from the main gene, sometimes on other chromosomes. Many scientists now argue that this overlapping and dispersal of genes, along with the swelling ranks of functional RNAs, renders the standard gene concept of the central dogma obsolete.

Long Live The Gene

Offering a radical new conception of the genome, Gingeras proposes shifting the focus away from protein-coding genes. Instead, he suggests that the fundamental units of the genome could be defined as functional RNA transcripts.

Since some of these transcripts ferry code for proteins as dutiful mRNAs, this new perspective would encompass traditional genes. But it would also accommodate new classes of functional RNAs as they’re discovered, while avoiding the confusion caused by several overlapping genes laying claim to a single stretch of DNA. The emerging picture of the genome “definitely shifts the emphasis from genes to transcripts,” agrees Mark B. Gerstein, a bioinformaticist at Yale University.

Scientists’ definition of a gene has evolved several times since Gregor Mendel first deduced the idea in the 1860s from his work with pea plants. Now, about 50 years after its last major revision, the gene concept is once again being called into question.

Theory Suggests That All Genes Affect Every Complex Trait
by Veronique Greenwood

Over the years, however, what scientists might consider “a lot” in this context has quietly inflated. Last June, Pritchard and his Stanford colleagues Evan Boyle and Yang Li (now at the University of Chicago) published a paper about this in Cell that immediately sparked controversy, although it also had many people nodding in cautious agreement. The authors described what they called the “omnigenic” model of complex traits. Drawing on GWAS analyses of three diseases, they concluded that in the cell types that are relevant to a disease, it appears that not 15, not 100, but essentially all genes contribute to the condition. The authors suggested that for some traits, “multiple” loci could mean more than 100,000. […]

For most complex conditions and diseases, however, she thinks that the idea of a tiny coterie of identifiable core genes is a red herring because the effects might truly stem from disturbances at innumerable loci — and from the environment — working in concert. In a new paper out in Cell this week, Wray and her colleagues argue that the core gene idea amounts to an unwarranted assumption, and that researchers should simply let the experimental data about particular traits or conditions lead their thinking. (In their paper proposing omnigenics, Pritchard and his co-authors also asked whether the distinction between core and peripheral genes was useful and acknowledged that some diseases might not have them.)

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What do we inherit? And from whom?

Our parents don’t just give us our genetics. They also give us microbes. Add on top of that the factors of epigenetics and environment that our parents give us and it makes one wonder about the complexity of it all.

Microbes are fascinating. Our entire life is dependent on them. And they make up a large part of our body mass. They don’t just impact our health but also our moods and who knows what else.

Or consider parasites. There is the toxoplasmosis gondii parasite which can have major impact on mammalian psychology, at least for rats and humans. Like rabies, toxoplasmosis changes behavior of the infected in order to spread the infection to others. These little buggers literally control your mind. Conniving clever creatures!

This gives a whole other perspective to parasite load. Parasites are more common in warm regions. It isn’t accidental that some of the poorest countries are also the warmest, as their populations have higher parasite loads. This effects both physical and mental health, stunting development and lowering IQ, among much else.

We’ve barely even researched this area. Most microbes and parasites remain unstudied. We have no clue what they do, good or bad. Most of the genetic material we carry in our bodies isn’t human, and that isn’t even including RNA with its bacterial origins. That should give you pause.

Anyway, genetics are only around 2% of the human genome, the rest being so-called Junk DNA, but scientists have come to realize it serves other purposes. By the way, viruses living in us like to snip out pieces of our DNA and mix them up, just for shits and giggles.

What all of this might mean genetically and epigenetically (i.e., across generations) is entirely up in the air. We live in a fascinating time of ignroance and discovery. Genetic determinists can put that in their pipe and smoke it.

On a positive note, this inheritance isn’t fatalism, as much of it can be changed as an adult. In particular, it should be relatively easy to improve gut health. Just introduce new microbes. And new foods that they like. Be sure your microbes are happy!

‘The Diet Myth,’ ‘The Good Gut’ and ‘The Hidden Half of Nature’
By Sonia Shah, NYT

“Using the improved detection capacity of genetic sequencing techniques, scientists have discovered that 100 trillion microscopic creatures live in and on the body, influencing everything from the intensity of our immune responses and our moods to our dietary preferences and propensity to gain weight.”

‘Infectious Madness,’ by Harriet A. Washington
By Meghan O’Rourke, NYT

“Indeed, a handful of researchers are wondering whether mental illnesses are really caused by our immune system’s response to powerful microbial infections. As Harriet A. Washington reports in her new book, “Infectious Madness: The Surprising Science of How We ‘Catch’ Mental Illness,” some researchers in the field believe microbes may be responsible not only for clear-cut diseases like typhoid and tuberculosis, but also for mental illnesses such as anorexia, obsessive-­compulsive disorder and schizophrenia — but in a less tidy manner. As she reports, research has found that 10 to 20 percent of mental illnesses, including autism, are partly caused by pathogens.”