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.)

2 thoughts on “What is a gene?

  1. Re this last quote- not just diseases, but complex traits in general may have this bizarre, mostly unknown soup method of being built from all along the genome, while also allowing environmental impact in nearly completely unknown ways through epigenetic and other processes. We know height and general intelligence (g) are this way. This insight puts new, greater pressure on genetic engineering, as the term genetic has gene at its core, with what turn out to be integral gross assumptions about SNPs that can be cut and pasted to specific ends. The work to modify the vast majority of corn, soybeans, cotton and other crops has been based on gene-based thinking about resisting insects and herbicides in specific ways. From a recent study, http://medcraveonline.com/APAR/APAR-08-00300.pdf , “Despite the numerous and overall benefits of genetically engineered crops, the questions raised by unwanted and unpredictable consequences about their safety concerns that may harm human, animal, and/or the ecosystem health require a long-term and a case-by-case transparent assessment before releasing the biotech crops into the food chain.” This on top of the risks we already should be considering, even assuming the ‘hard little ball’ theory of genes worked fine, i.e., “improving specific plant phenotypes through either mutagenesis in conventional breeding or transgenesis in GM crops may cause stress and weaken plant stress responses by altering the expression of untargeted genes…consumption of Bt corn byproducts reduced growth and increased mortality of Nontarget stream insects…the rise of glyphosate-resistant weed species as a result of GMO evolution…”

    Integral complexity keeps raising its head, needing a say across the whole spectrum of human concerns and being shunted aside. We have to be more forthright and more explicit about the massive relative difference between the modern liberal and conservative approaches to complexity in general, a fundamental neurological and philosophic difference. Complexity is the way our increasing, insurmountable interdependency reveals itself. The left-brained, don’t-worry-be-happy method of management is poised to kill us all.

    • “…require a long-term and a case-by-case transparent assessment before releasing the biotech crops into the food chain.”

      That is why I have such a strong attitude toward precautionary principle. This relates to my not being radical by personality, even as the times I live in lead me to radical thoughts. And this relates to why, in certain ways, I can be more ‘conservative’ than most conservatives.

      I actually worry about conserving, as did those like Thomas Paine. It is this sense of how precious is the world, a world we don’t fully understand and that is built on an ancient heritage (of genetics, epigenetics, and microbiome; of biosphere, ecosystems, and natural resources; et cetera) that shouldn’t be taken for granted.

      “The left-brained, don’t-worry-be-happy method of management is poised to kill us all.”

      Yep. As research shows, conservatives at least claim to be happier, not that self-reports are all that reliable. I suspect that in a sense conservatives are genuinely happier, if only for being more oblivious to the world around them. Other research shows that conservatives are less sensitively aware of their environments and other people, which allows them to be better focused and successful (or at least more obedient) within the established system.

      The problem is that reality is more complex than conservative ideology allows. And modern American conservatism has sacrificed the one saving grace of the conservative mind, that is the sense of precaution. Conservatism has become entirely unmoored from any real sense of the world, past or present. The conservative mind has become lost in dark fantasies of a haunted moral imagination.

      Asking an ideologically-entrenched conservative (especially those with authoritarian tendencies) to understand complex systems, from biology to climatology, is an almost impossible task. It’s hard enough dealing with crypto-conservative ‘liberals’ with their Jekyll and Hyde personalities.

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