In an ongoing effort to unravel the mysteries of DNA, I recently completed a class at UC Berkeley, “Introduction to Genetic Analysis.” This essay, “What is a Gene?” was part of my final. Although the question could easily pass as a Zen koan, I gave it a shot.
What is a Gene?
To paraphrase Nature reporter Helen Pearson, ‘gene’ is not your typical four-letter word. Unlike most four-letter words whose definitions are well understood, the definition of a gene remains elusive. The more scientists learn about genes, the more the definition seems to fray around the edges. A question such as ‘How many genes are in this organism?’ is difficult to answer conclusively without a consistent description. In 2006, one research group examined the results of 77 experiments counting the number of genes in the human genome; none produced the same result (Liolios et al, 2006 doi:10.1093/nar/gkj145). From the smallest virus with three functional genes to humans with approximately 22,000, counting genes is challenging.
With roots in Mendel’s research on garden peas, the term “gene” has evolved from its original definition of a “unit of inheritance” to one that reflects advances in molecular biology. A commonly accepted definition is that a gene is a region of nucleic acid that specifies an RNA or protein. This definition encompasses both single- and double-stranded DNA and RNA. Exons, coding regions of DNA and RNA that are translated into protein sequences, are found in most, but not all genes. To incorporate a finding that proteins can be produced from non-coding exon regions, some geneticists have added “flanking regulatory elements” to this definition (Pesole, 2008 doi:10.1016/j.gene.2008.03.010). This addition incorporates genetic curiosities such as the lac operon, which allows bacteria to digest lactose. Newer definitions may emphasize functional products—counting proteins or RNA—rather than specific DNA loci. More precise definitions that apply to specific types of organisms, e.g., eukaryotes, seem inevitable.
After the discovery of the structure of DNA by Watson and Crick, mechanisms describing DNA replication, transcription and translation quickly followed. DNA, which functions as a “parts list” of molecular information, stores an organism’s functional repertoire. The addition of molecular information to biology provided a physical basis for understanding heredity, which in turn led to the surprising finding that organisms share many genes in common. This commonality has provided insight into the evolution of various species. Through the lens of evolution, genes exist to convert the molecular information stored in DNA into self-sustaining multicellular organisms. Organisms with adaptive genes transmit their genetic information to the next generation to ensure the successful propagation of the species.
In 1955, the year Watson and Crick’s paper appeared, Einstein was asked to define “light quanta,” or what are now commonly called photons. His response was:
All these fifty years of conscious brooding have brought me no nearer to the answer to the question, ‘What are light quanta?’ Nowadays, every Tom, Dick and Harry thinks he knows it, but he is mistaken. (Born, 1971 The Born-Einstein Letters)
In the ensuing fifty years, particle physicists arrived at a consensus describing photons (the so-called Standard Model). In genetics, the results from the Human Genome Project in 2000 provide a foundation on which to build future results. A clearer answer to the question ‘What is a gene?’ is emerging. The answer to this question will provide more accurate interpretations of the similarities and differences between individuals and species.