The split gene theory is a theory of the origin of introns, long non-coding sequences in eukaryotic genes between the exons. The theory holds that the randomness of primordial DNA sequences would only permit small (< 600bp) open reading frames (ORFs), and that important intron structures and regulatory sequences are derived from stop codons. In this introns-first framework, the spliceosomal machinery and the nucleus evolved due to the necessity to join these ORFs (now "exons") into larger proteins, and that intronless bacterial genes are less ancestral than the split eukaryotic genes. The theory originated with Periannan Senapathy.
The theory provides solutions to key questions concerning the split gene architecture, including split eukaryotic genes, exons, introns, splice junctions, and branch points, based on the origin of split genes from random genetic sequences. It also provides possible solutions to the origin of the spliceosomal machinery, the nuclear boundary and the eukaryotic cell.
This theory led to the Shapiro–Senapathy algorithm, which provides the methodology for detecting the splice sites, exons and split genes in eukaryotic DNA, and which is the main method for detecting splice site mutations in genes that cause hundreds of diseases.
Split gene theory requires a separate origin of all eukaryotic species. It also requires that the simpler prokaryotes evolved from eukaryotes. This completely contradicts the scientific consensus about the formation of eukaryotic cells by endosymbiosis of bacteria. In 1994, Senapathy wrote a book about this aspect of his theory - The Independent Birth of Organisms. It proposed that all eukaryotic genomes were formed separately in a primordial pool. Dutch biologist Gert Korthoff criticized the theory by posing various problems that cannot be explained by a theory of independent origins. He pointed out that various eukaryotes need nurturing and called this the boot problem, in that even the initial eukaryote needed parental care. Korthoff notes that a large fraction of eukaryotes are parasites. Senapathys theory would require a coincidence to explain their existence. Senapathys theory cannot explain the strong evidence for common descent (homology, universal genetic code, embryology, fossil record.)