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Comparative genomics.

Hardison RC - PLoS Biol. (2003)

View Article: PubMed Central - PubMed

Affiliation: Center for Comparative Genomics and Bioinformatics at The Pennsylvania State University in University Park, Pennsylvania, USA. rch8@psu.edu <rch8@psu.edu>

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A complete genome sequence of an organism can be considered to be the ultimate genetic map, in the sense that the heritable characteristics are encoded within the DNA and that the order of all the nucleotides along each chromosome is known... However, knowledge of the DNA sequence does not tell us directly how this genetic information leads to the observable traits and behaviors (phenotypes) that we want to understand... Over such very large distances, the order of genes and the sequences regulating their expression are generally not conserved... At moderate phylogenetic distances (roughly 70–100 million years of divergence), both functional and nonfunctional DNA is found within the conserved DNA... These regions of conserved synteny have many genes from one human chromosome that match genes on a mouse chromosome, often in very similar orders... In most cases, the intron-exon structures are highly conserved... This extensive conservation in protein-coding regions may be expected, because many biochemical functions of humans should also be found in mouse... One class, occupying about 24% of the genome, is comprised of the repetitive elements that arose by transposition only on the human lineage... These particular insertions did not occur in mice, and thus they cannot align between human and mouse... As genome sequences from additional species are determined, the various possible explanations for this nonaligning, nonrepetitive DNA can be tested... The list includes several yeast species to compare with Saccharomyces cerevisiae, another Drosophila species and Anopheles to compare with Drosophila melanogaster, mouse to compare with human, and now C. briggsae to compare with C. elegans... Other approaches using multiple sequences from more closely related species substantially improve the resolving power of comparative genomics... Researchers may reasonably expect in the near future to have results of this comparative analysis readily available... By calibrating these results, such as estimated likelihoods of being under selection, likelihood of being a coding exon, etc., against known functional elements, the power of the comparative approaches should improve.

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Comparisons of Genomes at Different Phylogenetic Distances Are Appropriate to Address Different QuestionsA generalized phylogenetic tree is shown, leading to four different organisms, with A and D the most distantly related pairs. Examples of the types of questions that can be addressed by comparisons between genomes at the different distances are given in the boxes.
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pbio.0000058-g001: Comparisons of Genomes at Different Phylogenetic Distances Are Appropriate to Address Different QuestionsA generalized phylogenetic tree is shown, leading to four different organisms, with A and D the most distantly related pairs. Examples of the types of questions that can be addressed by comparisons between genomes at the different distances are given in the boxes.

Mentions: Different questions can be addressed by comparing genomes at different phylogenetic distances (Figure 1). Broad insights about types of genes can be gleaned by genomic comparisons at very long phylogenetic distances, e.g., greater than 1 billion years since their separation. For example, comparing the genomes of yeast, worms, and flies reveals that these eukaryotes encode many of the same proteins, and the nonredundant protein sets of flies and worms are about the same size, being only twice that of yeast (Rubin et al. 2000). The more complex developmental biology of flies and worms is reflected in the greater number of signaling pathways in these two species than in yeast. Over such very large distances, the order of genes and the sequences regulating their expression are generally not conserved. At moderate phylogenetic distances (roughly 70–100 million years of divergence), both functional and nonfunctional DNA is found within the conserved DNA. In these cases, the functional sequences will show a signature of purifying or negative selection, which is that the functional sequences will have changed less than the nonfunctional or neutral DNA (Jukes and Kimura 1984). Not only does comparative genomics aim to discriminate conserved from divergent and functional from nonfunctional DNA, this approach is also contributing to identifying the general functional class of certain DNA segments, such as coding exons, noncoding RNAs, and some gene regulatory regions. Examples of analyses at this distance include comparisons among enteric bacteria (McClelland et al. 2000), among several species of yeast (Cliften et al. 2001, 2003; Kellis et al. 2003), and between mouse and human (International Mouse Genome Sequencing Consortium 2002). The new comparison of the genomes of Caenorhabditis briggsae and Caenorhabditis elegans (Stein et al. 2003) falls in this category. In contrast, very similar genomes, such as those of humans and chimpanzees (separated by about 5 million years of evolution), are particularly apt for finding the key sequence differences that may account for the differences in the organisms. These are sequence changes under positive selection. Comparative genomics is thus a powerful and burgeoning discipline that becomes more and more informative as genomic sequence data accumulate.


Comparative genomics.

Hardison RC - PLoS Biol. (2003)

Comparisons of Genomes at Different Phylogenetic Distances Are Appropriate to Address Different QuestionsA generalized phylogenetic tree is shown, leading to four different organisms, with A and D the most distantly related pairs. Examples of the types of questions that can be addressed by comparisons between genomes at the different distances are given in the boxes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC261895&req=5

pbio.0000058-g001: Comparisons of Genomes at Different Phylogenetic Distances Are Appropriate to Address Different QuestionsA generalized phylogenetic tree is shown, leading to four different organisms, with A and D the most distantly related pairs. Examples of the types of questions that can be addressed by comparisons between genomes at the different distances are given in the boxes.
Mentions: Different questions can be addressed by comparing genomes at different phylogenetic distances (Figure 1). Broad insights about types of genes can be gleaned by genomic comparisons at very long phylogenetic distances, e.g., greater than 1 billion years since their separation. For example, comparing the genomes of yeast, worms, and flies reveals that these eukaryotes encode many of the same proteins, and the nonredundant protein sets of flies and worms are about the same size, being only twice that of yeast (Rubin et al. 2000). The more complex developmental biology of flies and worms is reflected in the greater number of signaling pathways in these two species than in yeast. Over such very large distances, the order of genes and the sequences regulating their expression are generally not conserved. At moderate phylogenetic distances (roughly 70–100 million years of divergence), both functional and nonfunctional DNA is found within the conserved DNA. In these cases, the functional sequences will show a signature of purifying or negative selection, which is that the functional sequences will have changed less than the nonfunctional or neutral DNA (Jukes and Kimura 1984). Not only does comparative genomics aim to discriminate conserved from divergent and functional from nonfunctional DNA, this approach is also contributing to identifying the general functional class of certain DNA segments, such as coding exons, noncoding RNAs, and some gene regulatory regions. Examples of analyses at this distance include comparisons among enteric bacteria (McClelland et al. 2000), among several species of yeast (Cliften et al. 2001, 2003; Kellis et al. 2003), and between mouse and human (International Mouse Genome Sequencing Consortium 2002). The new comparison of the genomes of Caenorhabditis briggsae and Caenorhabditis elegans (Stein et al. 2003) falls in this category. In contrast, very similar genomes, such as those of humans and chimpanzees (separated by about 5 million years of evolution), are particularly apt for finding the key sequence differences that may account for the differences in the organisms. These are sequence changes under positive selection. Comparative genomics is thus a powerful and burgeoning discipline that becomes more and more informative as genomic sequence data accumulate.

View Article: PubMed Central - PubMed

Affiliation: Center for Comparative Genomics and Bioinformatics at The Pennsylvania State University in University Park, Pennsylvania, USA. rch8@psu.edu <rch8@psu.edu>

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

A complete genome sequence of an organism can be considered to be the ultimate genetic map, in the sense that the heritable characteristics are encoded within the DNA and that the order of all the nucleotides along each chromosome is known... However, knowledge of the DNA sequence does not tell us directly how this genetic information leads to the observable traits and behaviors (phenotypes) that we want to understand... Over such very large distances, the order of genes and the sequences regulating their expression are generally not conserved... At moderate phylogenetic distances (roughly 70–100 million years of divergence), both functional and nonfunctional DNA is found within the conserved DNA... These regions of conserved synteny have many genes from one human chromosome that match genes on a mouse chromosome, often in very similar orders... In most cases, the intron-exon structures are highly conserved... This extensive conservation in protein-coding regions may be expected, because many biochemical functions of humans should also be found in mouse... One class, occupying about 24% of the genome, is comprised of the repetitive elements that arose by transposition only on the human lineage... These particular insertions did not occur in mice, and thus they cannot align between human and mouse... As genome sequences from additional species are determined, the various possible explanations for this nonaligning, nonrepetitive DNA can be tested... The list includes several yeast species to compare with Saccharomyces cerevisiae, another Drosophila species and Anopheles to compare with Drosophila melanogaster, mouse to compare with human, and now C. briggsae to compare with C. elegans... Other approaches using multiple sequences from more closely related species substantially improve the resolving power of comparative genomics... Researchers may reasonably expect in the near future to have results of this comparative analysis readily available... By calibrating these results, such as estimated likelihoods of being under selection, likelihood of being a coding exon, etc., against known functional elements, the power of the comparative approaches should improve.

Show MeSH