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Split gene theory
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Split gene theory
The split gene theory offers an explanation for the origin of eukaryotic introns. It suggests that random primordial DNA sequences would only permit short (< 600bp) open reading frames (ORFs) due to frequent stop codons. The short ORFs could have contained the short protein-coding exons observed in eukaryotic genes, whereas the intervening sequences with numerous stop codons could have formed long non-coding introns. In this introns-first framework, the spliceosomal machinery evolved due to the necessity to join exons into longer protein-coding sequences, and intron-less bacterial genes were derived from split eukaryotic genes through the loss of introns. The theory was introduced by Periannan Senapathy.
The theory provides solutions for the origin of split gene architecture, including exons, introns, splice junctions, and branch points from random genetic sequences. It also provides possible solutions for the origin of the spliceosomal machinery, the nuclear boundary, and the eukaryotic cell from prebiotic chemistry.
This theory led to the Shapiro–Senapathy algorithm, which provides a methodology for detecting splice sites in eukaryotic DNA, and has been used to find splice site mutations that cause hundreds of diseases.
The split gene theory 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 multiple eukaryotic genomes originated independently from a primordial pool of split genes. 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. Senapathy's theory would require a coincidence to explain their existence. Senapathy's theory cannot explain the strong evidence for common descent (homology, universal genetic code, embryology, fossil record.)
Genes of all organisms, except bacteria, consist of short protein-coding regions (exons) interrupted by long sequences (introns). When a gene is expressed, its DNA sequence is copied into a "primary RNA" sequence by the enzyme RNA polymerase. Then the "spliceosome" machinery physically removes the introns from the RNA copy of the gene by the process of splicing, leaving only a contiguously connected series of exons, which becomes messenger RNA (mRNA). This mRNA is now read by the ribosome, which produces the encoded protein. Thus, although introns are not physically removed from a gene, a gene's sequence is read as if introns were not present.
Exons are usually short, with an average length of about 120 bases (e.g. in human genes). Intron lengths vary widely from 10 to 500,000, but exon lengths have an upper bound of about 600 bases in most eukaryotes. Because exons code for protein sequences, they are important for the cell, yet constitute only ~2% of the sequences. Introns, in contrast, constitute 98% of the sequences but seem to have few crucial functions, except for enhancer sequences and developmental regulators in rare instances.
Until Philip Sharp and Richard Roberts discovered introns within eukaryotic genes in 1977, it was believed that the coding sequence of all genes was always in one single stretch, bounded by a single long ORF. The discovery of introns was a profound surprise, which instantly brought up the questions of how, why and when the introns came into the eukaryotic genes.
It soon became apparent that a typical eukaryotic gene was interrupted at many locations by introns, dividing the coding sequence into many short exons. Also surprising was that the introns were long, as long as hundreds of thousands of bases. These findings prompted the questions of why many introns occur within a gene (for example, ~312 introns occur in the human gene TTN), why they are long, and why exons are short.
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Split gene theory
The split gene theory offers an explanation for the origin of eukaryotic introns. It suggests that random primordial DNA sequences would only permit short (< 600bp) open reading frames (ORFs) due to frequent stop codons. The short ORFs could have contained the short protein-coding exons observed in eukaryotic genes, whereas the intervening sequences with numerous stop codons could have formed long non-coding introns. In this introns-first framework, the spliceosomal machinery evolved due to the necessity to join exons into longer protein-coding sequences, and intron-less bacterial genes were derived from split eukaryotic genes through the loss of introns. The theory was introduced by Periannan Senapathy.
The theory provides solutions for the origin of split gene architecture, including exons, introns, splice junctions, and branch points from random genetic sequences. It also provides possible solutions for the origin of the spliceosomal machinery, the nuclear boundary, and the eukaryotic cell from prebiotic chemistry.
This theory led to the Shapiro–Senapathy algorithm, which provides a methodology for detecting splice sites in eukaryotic DNA, and has been used to find splice site mutations that cause hundreds of diseases.
The split gene theory 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 multiple eukaryotic genomes originated independently from a primordial pool of split genes. 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. Senapathy's theory would require a coincidence to explain their existence. Senapathy's theory cannot explain the strong evidence for common descent (homology, universal genetic code, embryology, fossil record.)
Genes of all organisms, except bacteria, consist of short protein-coding regions (exons) interrupted by long sequences (introns). When a gene is expressed, its DNA sequence is copied into a "primary RNA" sequence by the enzyme RNA polymerase. Then the "spliceosome" machinery physically removes the introns from the RNA copy of the gene by the process of splicing, leaving only a contiguously connected series of exons, which becomes messenger RNA (mRNA). This mRNA is now read by the ribosome, which produces the encoded protein. Thus, although introns are not physically removed from a gene, a gene's sequence is read as if introns were not present.
Exons are usually short, with an average length of about 120 bases (e.g. in human genes). Intron lengths vary widely from 10 to 500,000, but exon lengths have an upper bound of about 600 bases in most eukaryotes. Because exons code for protein sequences, they are important for the cell, yet constitute only ~2% of the sequences. Introns, in contrast, constitute 98% of the sequences but seem to have few crucial functions, except for enhancer sequences and developmental regulators in rare instances.
Until Philip Sharp and Richard Roberts discovered introns within eukaryotic genes in 1977, it was believed that the coding sequence of all genes was always in one single stretch, bounded by a single long ORF. The discovery of introns was a profound surprise, which instantly brought up the questions of how, why and when the introns came into the eukaryotic genes.
It soon became apparent that a typical eukaryotic gene was interrupted at many locations by introns, dividing the coding sequence into many short exons. Also surprising was that the introns were long, as long as hundreds of thousands of bases. These findings prompted the questions of why many introns occur within a gene (for example, ~312 introns occur in the human gene TTN), why they are long, and why exons are short.