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Genomics (Comparative)

dna organisms sequences genome

The study of an organism's total complement of genetic material, called its genome, has become indispensable for shedding light on its biochemistry, physiology, and patterns of inheritance. Even more can be gained by comparing the genomes of multiple organisms to discern how their DNA sequences have changed over evolutionary time. This technique has become increasingly valuable with the explosion of genome sequencing activity in recent years. Today, hundreds of complete or near-complete genome sequences, ranging from simple microbes to human, have been deposited in scientific databases around the world.

All life on Earth has a common history, reflected by its common biochemical basis in DNA. Different organisms vary in their DNA sequences, of course, but perhaps not so much as one might think. Some of the genes controlling very basic biological tasks, such as the mechanism by which DNA is transcribed into RNA to code the proteins that determine function, originate with the Archaea, microorganisms believed to be the most direct descendants of the first living things. The genome of the humble mouse is 85 % identical to our own. Our closest relatives, the chimpanzees, differ from us genetically by only about 1%, a testimony to the incredible power of a relatively small amount of DNA.

The degree of disparity in the genomes of different organisms reflects their phylogenetic relationship; that is, their relative distances from one another and position on the branches of life's "family tree". Evolutionary biologists use this information to determine whether organisms are descended from a common ancestor, and at what point the different lineages divided. If the same gene is present in two organisms, they are presumed to have a common ancestor. The more the DNA sequences have changed since that point, the longer the two species have been evolving independently.

An example of the use of this technique was the comparison in the late 1990s of DNA from Neanderthal remains, modern humans and chimpanzees. The analysis yielded the conclusion that modern humans almost certainly did not descend directly from Neanderthals, as had once been thought, but rather shared a common ancestor with this earlier hominid.

Although the evidence is preliminary and far from conclusive, published reports of genome analysis in late 2002 provided evidence that early migrant populations of humanoids may have been able to intermix with established or indigenous humanoid populations to a greater degree than previously believed.

Genome analysis helps to distinguish physical similarities derived from common ancestry from those that have evolved separately in response to a similar environment, a phenomenon called convergent evolution. An example of convergent evolution can be seen in the fauna of Australia, where marsupials diverged to fill ecological niches dominated by placental mammals on other continents. As a result, Australia has marsupial mice, marsupial wolves, and kangaroos, which are the marsupial equivalent of deer and antelopes.

Comparative genomics has a vital role to play in research contributing to human health. The mouse is a useful model organism for biomedical research because of the similarities of its genome to that of humans. At the same time, unlike humans, the well-studied mouse has been bred over time into genetically identical strains, and its environment may be strictly controlled. These factors combine to reduce the potential sources of uncertainty about what might be causing a given result.

Almost every human gene has an exact counterpart in the mouse, despite the fact that the chromosomes are arranged differently. The differences in the species arise primarily not from the identity of the genes, but from the exact sequences that make them up, resulting in a change in the proteins that are built when the DNA is transcribed. Sequence changes reflect mutations that may have had an effect on the organism's ability to survive and reproduce, the driving force of evolution by natural selection. When scientists find a mutation in a mouse gene that is associated with the trait they are studying, they look for a similar DNA sequence in humans to find the corresponding human gene.

Comparing the billions of nucleotides that make up organisms' DNA sequences to tease out sequences with similar functions requires powerful database search engines and sophisticated software. The task is complex, and fraught with the possibility of error. First, since the sequence of a given gene is not expected to be identical between species, scientists must determine how close a match is close enough. In many cases throughout evolutionary history, genes have become duplicated, and then their functions diverge. Researchers look for relationships between genes in such a lineage just as they seek to place related organisms in a phylogenetic tree. A large proportion of genetic material, called "selfish DNA", has no apparent function in the organism at all, but rather exists merely to propagate itself from one generation to the next. The rigorous requirements for sequence analysis have given rise to a specialized discipline called bioinformatics, combining high-throughput computing with an extensive knowledge of biology.

Resources

Books

Beurton, Peter, Raphael Falk, Hans-Jörg Rheinberger., eds. The Concept of the Gene in Development and Evolution. Cambridge, UK: Cambridge University Press, 2000.

Lewin, B. Genes. 7th. ed. New York, Oxford University Press Inc., 2000

Periodicals

Fraser, C.M., J. Eisen, R.D. Fleischmann, K.A. Ketchum, and S. Peterson. "Comparative Genomics and Understanding of Microbial Biology." Emerging Infectious Diseases 6, no. 5 (September-October 2000).

Veuille, E. "Genetics and the evolutionary process." C. R. Acad. Sci III 323, no.12 (December 2000):1155–65.


Sherri Chasin Calvo

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