Datasets for evolutionary comparative genomics
© BioMed Central Ltd 2005
Published: 28 July 2005
Many decisions about genome sequencing projects are directed by perceived gaps in the tree of life, or towards model organisms. With the goal of a better understanding of biology through the lens of evolution, however, there are additional genomes that are worth sequencing. One such rationale for whole-genome sequencing is discussed here, along with other important strategies for understanding the phenotypic divergence of species.
Bioinformaticists and computational biologists working in the field of comparative genomics are largely dependent on datasets generated by others. Working with available data opens up desires for complementary datasets to fill knowledge gaps. In addition to writing grants for experimental laboratories and molecular biology supplies, one can also write an opinion piece to convince others to do some of the dirty work for you; this is what I am attempting to do here. Comparative genomics starts with sequencing. Many have suggested gaps in the tree of life, where additional genome projects will augment current knowledge, either to shorten long 'branches' on the tree of sequenced genomes or to complement existing genome projects. For example, there remain huge gaps in our knowledge of archaea. But with the faith that these gaps will ultimately be filled in, in this article I focus on alternative strategies for directing genomic resources so as to answer fundamental questions in evolution.
The tape of life
A whole class of genomic experiments can be hypothesized through what can be called the 'tape of life' question. Stephen J. Gould wrote in his book Wonderful Life , "Wind back the tape of life to the early days of the Burgess shale; let it play again from an identical starting point, and the chance becomes vanishingly small that anything like human intelligence would grace the replay". At the molecular level, the tape of life has been played in parallel. Different species have gone from a similar ancestral point to a similar derived phenotype. In these cases, are the same molecules and pathways driving the phenotypic evolution? Comparative genomics gives us unprecedented opportunities to answer such questions.
A few studies have tried to address the tape-of-life question through analysis of a single gene, such as the melanocortin-1 receptor (MC1R). This receptor plays a role in pigmentation and body/hair color, representing an obvious link between selectable genotype and phenotype. MC1R has been demonstrated to be under such selective pressure in various birds  and mammals . In another set of studies, the transcription factor Pitx1, involved in hindlimb formation, has been implicated in parallel evolution of morphologically very distinct types of stickleback fish . At a genomic level, there are whole classes of experiments that can be proposed where phenotypic evolution is the driving force.
Rapid phenotypic evolution
Examination of the tape-of-life question or rapid phenotypic evolution does not need to involve entire genome sequencing. Large-scale full-length cDNA [12, 13] and upstream promoter sequence can be generated more cheaply but contains much of the relevant functional information. The molecular basis for changes in coding sequence function, gene expression, and possibly alternative splicing is likely to be contained within such data. Ultimately, population-level data in the form of single nucleotide polymorphisms (SNPs) linked to biogeography will also be desirable, to shed light on the process of speciation.
In addition to coding-sequence evolution, changes in alternative splicing patterns and gene-expression levels and patterns can also contribute to lineage-specific diversification. Large-scale inter-specific datasets that characterize relative splice-site usage or splice-variant frequencies would be valuable. An initial study comparing alternative splicing patterns in mouse, rat, and human led to the conclusion that alternative splice variants, like gene duplicates, have been used as a testbed for evolutionary novelty .
Changes in gene expression have become the leading candidates as drivers of evolutionary novelty, dating back to Allan Wilson's attempt to explain the phenotypic divergence between human and chimpanzee . Pioneering work on the evolution of regulatory networks in echinoderms has pointed to a major role for changes in the expression of key regulatory proteins during development in driving morphological change . A systematic examination of gene-expression changes in higher primates has also been presented . The molecular variation in the human population that affects gene expression that is subject to the diversifying selection and fixation seen in inter-specific studies is also being characterized  and can be related to chimpanzee sequences in a bid to understand lineage-specific evolution. Extending this in a well controlled study across larger portions of the tree of life (initially at the inter-specific level) is warranted.
Both relative gene-expression levels and relative alternative splicing levels are continuous variables, unlike sequences that are discretely A, C, G or T. There are methods for reconstructing such values over a phylogenetic tree and parsing changes onto branches, coupled to a reconstruction of the regulatory sequences that govern such processes (see, for example, ). The power of harnessing phylogenetic information not only provides an understanding of the molecular basis for organismal phenotypic divergence but can also be used to reduce the background 'noise' in attempts to understand basic principles of transcriptional regulation, mRNA splicing, and protein folding and function [19, 20].
Even within the completed genomes that we already have, there are many unknown genes. Phylogenetic focusing (systematically attempting to sequence such genes from closely related species) will help us understand how they evolved, their function, and the evolution of novel genes in general. This can also be applied to rare protein structures, in order to understand the process of neostructuralization by searching for phylogenetic intermediates that provide a 'missing link' sequence. Phylogenetic focusing will be greatly aided by the establishment of local DNA banks containing genomic DNA from regionally specific species. This will also aid nations and their regions in understanding local biodiversity.
Ohno , and subsequently Lynch and Conery , proposed a major role for gene duplication in the generation of evolutionary novelty. Wilson and Davidson and colleagues have done the same for gene expression [15, 16]; the Lee lab has done the same for alternative splicing . All are probably right to some degree, as evolution is opportunistic and different regulatory mechanisms have potential different selectable outcomes. Generating datasets that enable us to integrate such knowledge and output better models (also drawing on work in population genetics, structural genomics, and systems biology) will allow a better understanding of biology, with evolution at its core. This article aims to continue a dialog between experimental and computational researchers towards the aim of a better understanding of genomes, and to encourage experimentalists to provide the community with even more varieties of genomic data.
- Gould SJ: Wonderful Life: The Burgess Shale and the Nature of History. 1989, New York: W.W. Norton & CompanyGoogle Scholar
- Mundy NI, Badcock NS, Hart T, Scribner K, Janssen K, Nadeau NJ: Conserved genetic basis of a quantitative plumage trait involved in mate choice. Science. 2004, 303: 1870-1873. 10.1126/science.1093834.PubMedView ArticleGoogle Scholar
- Nachman MW, Hoekstra HE, D'Agostino SL: The genetic basis of adaptive melanism in pocket mice. Proc Natl Acad Sci USA. 2003, 100: 5268-5273. 10.1073/pnas.0431157100.PubMedPubMed CentralView ArticleGoogle Scholar
- Shapiro MD, Marks ME, Peichel CL, Blackman BK, Nereng KS, Jonsson B, Schluter D, Kingsley DM: Genetic and developmental basis of evolutionary pelvic reduction in threespine sticklebacks. Natur. 2004, 428: 717-723. 10.1038/nature02415.View ArticleGoogle Scholar
- Liu FG, Miyamoto MM, Freire NP, Ong PQ, Tennant MR, Young TS, Gugel KF: Molecular and morphological supertrees for eutherian (placental) mammals. Science. 2001, 291: 1786-1789. 10.1126/science.1056346.PubMedView ArticleGoogle Scholar
- Hatfield JR, Samuelson DA, Lewis PA, Chisholm M: Structure and presumptive function of the iridocorneal angle of the West Indian manatee (Trichechus manatus), short-finned pilot whale (Globicephala macrorhynchus), hippopotamus (Hippopotamus amphibius), and African elephant (Loxodonta africana). Vet Opthalmol . 2003, 6: 35-43. 10.1046/j.1463-5224.2003.00262.x.View ArticleGoogle Scholar
- Salzburger W, Meyer A: The species flocks of East African cichlid fishes: recent advances in molecular phylogenetics and population genetics. Naturwissenschaften. 2004, 91: 277-290. 10.1007/s00114-004-0528-6.PubMedGoogle Scholar
- Stiassny MLJ, Meyer A: Cichlids of the rift lakes. Sci Am. 1999, 64-69.Google Scholar
- DOE Joint Genome Institute - Why Sequence Cichlid Fish?. [http://www.jgi.doe.gov/sequencing/why/CSP2006/cichlids.html]
- Kurten B: The evolution of the polar bear, Ursus maritimus. Acta Zoologica Fennica. 1964, 108: 1-26.Google Scholar
- Talbot SL, Shields GF: A phylogeny of the bears (Ursidae) inferred from complete sequences of three mitochondrial genes. Mol Phylogenet Evol. 1996, 5: 567-575. 10.1006/mpev.1996.0051.PubMedView ArticleGoogle Scholar
- Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H, Kondo S, Nikaido I, Osato N, Saito R, Suzuki H, et al: Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNA. Nature. 2002, 420: 563-573. 10.1038/nature01266.PubMedView ArticleGoogle Scholar
- Crawford DL: Functional genomics does not have to be limited to a few select organisms. Genome Biol. 2001, 2: interactions1001.1-1001.2. 10.1186/gb-2001-2-1-interactions1001.View ArticleGoogle Scholar
- Modrek B, Lee CJ: Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and/or loss. Nature Genet. 2003, 34: 177-180. 10.1038/ng1159.PubMedView ArticleGoogle Scholar
- King MC, Wilson AC: Evolution at two levels in humans and chimpanzees. Science. 1975, 188: 107-116.PubMedView ArticleGoogle Scholar
- Hinman VF, Nguyen AT, Cameron RA, Davidson EH: Developmental gene regulatory network architecture across 500 million years of echinoderm evolution. Proc Natl Acad Sci USA. 2003, 100: 13356-13361. 10.1073/pnas.2235868100.PubMedPubMed CentralView ArticleGoogle Scholar
- Enard W, Khaitovich P, Klose J, Zollner S, Heissig F, Giavalisco P, Nieselt-Struwe K, Muchmore E, Varki A, Ravid R, et al: Intra- and interspecific variation in primate gene expression patterns. Science. 2002, 296: 340-343. 10.1126/science.1068996.PubMedView ArticleGoogle Scholar
- Rockman MV, Wray GA: Abundant raw material for cis-regulatory evolution in humans. Mol Biol Evol. 2002, 19: 1991-2004.PubMedView ArticleGoogle Scholar
- Rossnes R, Eidhammer I, Liberles DA: Phylogenetic reconstruction of ancestral character states for gene expression and mRNA splicing data. BMC Bioinformatics. 2005, 6: 127-10.1186/1471-2105-6-127.PubMedPubMed CentralView ArticleGoogle Scholar
- Fukami-Kobayashi K, Schreiber DR, Benner SA: Detecting compensatory covariation signals in protein evolution using reconstructed ancestral sequences. J Mol Biol. 2002, 319: 729-743. 10.1016/S0022-2836(02)00239-5.PubMedView ArticleGoogle Scholar
- Ohno S: Evolution by Gene Duplication. 1970, Berlin: SpringerView ArticleGoogle Scholar
- Lynch M, Conery JS: The origins of genome complexity. Science. 2003, 302: 1401-1404. 10.1126/science.1089370.PubMedView ArticleGoogle Scholar