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Human, mouse shared common ancestor 75 million years ago
Mouse and human genome rearrangements occurred more commonly than previously believed.
A LEADING expert in computational biology at the University of California, San Diego (UCSD) estimates that it took many more evolutionary genome rearrangements than previously thought — both large and small — to account for differences in the human and mouse genomes.
In the journal Nature, Pavel Pevzner of Jacobs School of Engineering and other scientists in the 31-institution Mouse Genome Sequencing Consortium published a near-final genetic blueprint of a mouse, together with the first comparative analysis of the mouse and human genomes.
In a companion paper published in Genome Research journal, Pevzner and Glenn Tesler, project scientist, analyse human-mouse genome rearrangements for insights about the evolution of mammals, and outline their development of a new algorithm to differentiate macro and micro-level genome rearrangements.
Their conclusion: although the mouse and human genomes are very similar, genome rearrangements occurred more commonly than previously believed, accounting for the evolutionary distance between human and mouse from a common ancestor 75 million years ago.
"The human and mouse genome sequences can be viewed as two decks of cards obtained by re-shuffling from a master deck — an ancestral mammalian genome," said Pevzner. "And in addition to the major rearrangements that shuffle large chunks of the gene pool, our research confirmed another process that shuffles only small chunks."
"We now estimate over 245 major rearrangements that represent dramatic evolutionary events," added Tesler.
Biologists and medical doctors study two kinds of rearrangements: clinical and evolutionary. Clinical rearrangements are manifested as a rather common chromosomal abnormality, associated with such diseases as Down syndrome, cancer, and infertility. Many healthy individuals also carry an asymptomatic chromosomal rearrangement.
Evolutionary genome rearrangements, on the other hand, have occurred only about once or twice every million years in the course of mammalian evolution.
"While clinical rearrangements affect a single individual, evolutionary rearrangements affect all individuals in a particular species and lead to speciation, for example, to separation of human and mouse lineages," explained Pevzner.
"The human and mouse genome sequences can be viewed as two decks of cards obtained by re-shuffling from a master deck an ancestral mammalian genome."
Because the mouse carries virtually the same set of genes as the human but can be used in laboratory research, information about the mouse genome will allow scientists to test experimentally and learn more about the function of human genes, leading to better understanding of human disease and improved treatments and cures.
Said Pevzner: "If clinical and evolutionary rearrangements are well related (which is still an open question), then studying evolution could yield insights about cancer and infertility, and vice versa."
In Nature, scientists comparing human and mouse genomes found that more than 90 per cent of the mouse genome could be lined up with a region on the human genome. That is because the gene order in the two genomes is often well preserved over large stretches, called `conserved synteny.'
In fact, the mouse genome could be parsed into some 350 segments, or chapters, for which there is a corresponding chapter in the human genome.
For example, chromosome 3 of the mouse genome has chapters from human chromosomes 1, 3, 4, 8 and 13, and chromosome 16 of the mouse has chapters from human chromosomes 3, 21, 22 and 16. Although virtually all the human and mouse sequences can be aligned at the level of large chapters, only 40 percent of the mouse and the human sequences can be lined up at the level of sentences and words.
Even within this 40 percent, there has been considerable editing, as evolution relentlessly tinkers with the genome. The change is so great in most places that only with very sensitive tools can scientists discern the relationships.
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