regions of a gene such as enhancers do not necessarily have to be close to the coding sequence on the linear molecule because the intervening DNA can be looped out to bring the gene and its regulatory region into proximity. Similarly, a gene's introns can be much larger than its exons. Regulatory regions can even be on entirely different chromosomes and operate in trans to allow regulatory regions on one chromosome to come in contact with target genes on another chromosome. Early work in molecular genetics suggested the concept that one gene makes one protein. This concept (originally called the one gene-one enzyme hypothesis) emerged from an influential 1941 paper by George Beadle and Edward Tatum on experiments with mutants of the fungus Neurospora crassa. Norman Horowitz, an early colleague on the Neurospora research, reminisced in 2004 that "these experiments founded the science of what Beadle and Tatum called biochemical genetics. In actuality they proved to be the opening gun in what became molecular genetics and all the developments that have followed from that". The one gene-one protein concept has been refined since the discovery of genes that can encode multiple proteins by alternative splicing and coding sequences split in short section across the genome whose mRNAs are concatenated by trans-splicing. A broad operational definition is sometimes used to encompass the complexity of these diverse phenomena, where a gene is defined as a union of genomic sequences encoding a coherent set of potentially overlapping functional products. This definition categorizes genes by their functional products (proteins or RNA) rather than their specific DNA loci, with regulatory elements classified as gene-associated regions. Overlap between genes It is also possible for genes to overlap the same DNA sequence and be considered distinct but overlapping genes. The current definition of an overlapping gene is different across eukaryotes, prokaryotes, and viruses. In Eukaryotes they have recently been defined as "when at least one nucleotide is shared between the outermost boundaries of the primary transcripts of two or more genes, such that a DNA base mutation at the point of overlap would affect transcripts of all genes involved in the overlap." In Prokaryotes and Viruses they have recently been defined as "when the coding sequences of two genes share a nucleotide either on the same or opposite strands." Gene expression In all organisms, two steps are required to read the information encoded in a gene's DNA