How Many Genes Do Humans Have?

In February 2001, two largely independent draft versions of the human genome were published. Both studies estimated that there are 30,000 to 40,000 genes in the human genome, roughly one-third the number of previous estimates. More recently scientists estimated that there are less than 30,000 human genes. However, we still have to make guesses at the actual number of genes, because not all of the human genome sequence is annotated and not all of the known sequence has been assigned a particular position in the genome. So, how do scientists estimate the number of genes in a genome? For the most part, they look for tell-tale signs of genes in a DNA sequence. These include: open reading frames, stretches of DNA, usually greater than 100 bases, that are not interrupted by a stop codon such as TAA, TAG or TGA; start codons such as ATG; specific sequences found at splice junctions, a location in the DNA sequence where RNA removes the non-coding areas to form a continuous gene transcript for translation into a protein; and gene regulatory sequences. This process is dependent on computer programs that search for these patterns in various sequence databases and then make predictions about the existence of a gene.

From One Gene–One Protein to a More Global Perspective Only a small percentage of the 3 billion bases in the human genome becomes an expressed gene product. However, of the approximately 1 percent of our genome that is expressed, 40 percent is alternatively spliced to produce multiple proteins from a single gene. Alternative splicing refers to the cutting and pasting of the primary mRNA transcript into various combinations of mature mRNA. Therefore the one gene–one protein theory, originally framed as "one gene–one enzyme", does not precisely hold. With so much DNA in the genome, why restrict transcription to a tiny portion, and why make that tiny portion work overtime to produce many alternate transcripts? This process may have evolved as a way to limit the deleterious effects of mutations. Genetic mutations occur randomly, and the effect of a small number of mutations on a single gene may be minimal. However, an individual having many genes each with small changes could weaken the individual, and thus the species. On the other hand, if a single mutation affects several alternate transcripts at once, it is more likely that the effect will be devastating—the individual may not survive to contribute to the next generation. Thus, alternate transcripts from a single gene could reduce the chances that a mutated gene is transmitted.