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dc.contributor.authorMaxwell, Evan K.
Schnitzler, Christine E.
Havlak, Paul
Putnam, Nicholas H.
Nguyen, Anh-Dao
Moreland, R. Travis
dc.date.accessioned 2017-08-17T19:19:41Z
dc.date.available 2017-08-17T19:19:41Z
dc.date.issued 2014
dc.identifier.citation Maxwell, Evan K., Schnitzler, Christine E., Havlak, Paul, et al.. "Evolutionary profiling reveals the heterogeneous origins of classes of human disease genes: implications for modeling disease genetics in animals." BMC Evolutionary Biology, 14, (2014) BioMed Central: https://doi.org/10.1186/s12862-014-0212-1.
dc.identifier.urihttps://hdl.handle.net/1911/97336
dc.description.abstract Background: The recent expansion of whole-genome sequence data available from diverse animal lineages provides an opportunity to investigate the evolutionary origins of specific classes of human disease genes. Previous studies have observed that human disease genes are of particularly ancient origin. While this suggests that many animal species have the potential to serve as feasible models for research on genes responsible for human disease, it is unclear whether this pattern has meaningful implications and whether it prevails for every class of human disease. Results: We used a comparative genomics approach encompassing a broad phylogenetic range of animals with sequenced genomes to determine the evolutionary patterns exhibited by human genes associated with different classes of disease. Our results support previous claims that most human disease genes are of ancient origin but, more importantly, we also demonstrate that several specific disease classes have a significantly large proportion of genes that emerged relatively recently within the metazoans and/or vertebrates. An independent assessment of the synonymous to non-synonymous substitution rates of human disease genes found in mammals reveals that disease classes that arose more recently also display unexpected rates of purifying selection between their mammalian and human counterparts. Conclusions: Our results reveal the heterogeneity underlying the evolutionary origins of (and selective pressures on) different classes of human disease genes. For example, some disease gene classes appear to be of uncommonly recent (i.e., vertebrate-specific) origin and, as a whole, have been evolving at a faster rate within mammals than the majority of disease classes having more ancient origins. The novel patterns that we have identified may provide new insight into cases where studies using traditional animal models were unable to produce results that translated to humans. Conversely, we note that the larger set of disease classes do have ancient origins, suggesting that many non-traditional animal models have the potential to be useful for studying many human disease genes. Taken together, these findings emphasize why model organism selection should be done on a disease-by-disease basis, with evolutionary profiles in mind.
dc.language.iso eng
dc.publisher BioMed Central
dc.rightsThis article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0
dc.title Evolutionary profiling reveals the heterogeneous origins of classes of human disease genes: implications for modeling disease genetics in animals
dc.type Journal article
dc.citation.journalTitle BMC Evolutionary Biology
dc.subject.keywordModel organism selection
Human disease genes
Evolutionary genetics
Comparative genomics
dc.citation.volumeNumber 14
dc.identifier.digital Evolutionary_profiling
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.1186/s12862-014-0212-1
dc.identifier.pmcid PMC4219131
dc.identifier.pmid 25281000
dc.type.publication publisher version
dc.citation.articleNumber 212


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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Except where otherwise noted, this item's license is described as This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.