Maintenance of functional equivalence during paralogous Hox gene evolution

Greer, Joy M.; Puetz, John; Thomas, Kirk R.; Capecchi, Mario R.

doi:10.1038/35001077

Cited by 236 publications

(181 citation statements)

References 29 publications

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“…However other Hox PG1-4 mutant phenotypes are very subtle indeed. This is likely due to partial redundancy between Hox paralogs, as has been shown most clearly for the PG3 genes (Greer et al, 2000). It also explains why no Hox mutants have been identified in zebrafish mutant screens to date: with the possible exception of the segmental defects associated with the mouse Hoxa1 mutant (reviewed in Morrison, 1998), no single Hox loss-of-function phenotype is likely to be severe enough to have been isolated in the morphology-or even marker-based screens performed in the zebrafish thus far.…”

Section: Hox Gene Function: Specifying Rhombomere Identity and Segmenmentioning

confidence: 83%

Constructing the hindbrain: Insights from the zebrafish

Moens¹,

Prince²

2002

Developmental Dynamics

197

179

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The hindbrain is responsible for controlling essential functions such as respiration and heart beat that we literally do not think about most of the time. In addition, cranial nerves projecting from the hindbrain control muscles in the jaw, eye, and face, and receive sensory input from these same areas. In all vertebrates that have been studied, the hindbrain passes through a segmented phase shortly after the neural tube has formed, with a series of seven bulges-the rhombomeres-forming along the anterior-posterior extent of the neural tube. Our current understanding of vertebrate hindbrain development comes from integrating data from several model systems. Work on the chick has helped us to understand the cell biology of the rhombomeres, whereas the power of mouse molecular genetics has allowed investigation of the molecular mechanisms underlying their development. This review focuses on the special insights that the zebrafish system has provided to our understanding of hindbrain development. As we will discuss, work in the zebrafish has elucidated inductive events that specify the presumptive hindbrain domain and has identified genes required for hindbrain segmentation and the specification of segment identities.

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Section: Hox Gene Function: Specifying Rhombomere Identity and Segmenmentioning

confidence: 83%

Constructing the hindbrain: Insights from the zebrafish

Moens¹,

Prince²

2002

Developmental Dynamics

197

179

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“…Here, a recurring theme is functional divergence through diverging gene expression rather than diverging biochemical function [59][60][61][62] . A case in point are the duplicate Hox genes Hoxa3 and Hoxd3 59 . The developmental defects found in loss-of-function mutations of either gene are very different.…”

Section: Vertebrate Diversificationmentioning

confidence: 99%

“…Hoxa3 mutants are defective in pharyngeal tissues, whereas Hoxd3 mutants show malformed cervical vertebrae 63,64 . Their biochemical functions appear identical, such that quantitative expression changes may be responsible for their functional differences 59 . Similarly, the coding regions of the duplicate mouse Hoxa1 and Hoxb1 genes are nearly identical, yet they have different functions in hindbrain development mediated by different spatiotemporal gene expression 62 .…”

Section: Vertebrate Diversificationmentioning

confidence: 99%

Gene duplications, robustness and evolutionary innovations

Wagner

2008

BioEssays

115

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Gene duplications, robustness and evolutionary innovations Gene duplications, robustness and evolutionary innovations AbstractMutational robustness facilitates evolutionary innovations. Gene duplications are unique kinds of mutations, in that they generally increase such robustness. The frequent association of gene duplications in regulatory networks with evolutionary innovation is thus a special case of a general mechanism linking innovation to robustness. The potential power of this mechanism to promote evolutionary innovations on large time scales is illustrated here with several examples. These include the role of gene duplications in the vertebrate radiation, flowering plant evolution and heart development, which encompass some of the most striking innovations in the evolution of life. Gene duplications, robustness, and evolutionary innovationsAndreas Wagner AbstractMutational robustness facilitates evolutionary innovations in biological systems. Gene duplications are unique kinds of mutations, in that they generally increase such robustness. The frequent association of gene duplications in regulatory networks with evolutionary innovation thus exemplifies a general mechanism linking innovation to robustness. I illustrate the potential power of this mechanism on large time scales with the role of gene duplications in the vertebrate radiation, flowering plant evolution, and heart development, which encompass some of the most striking innovations in the evolution of life. Mutational robustnessMutational robustness is a biological's system ability to withstand mutations. Such robustness exists on multiple levels of biological organization. A case in point are random mutagenesis experiments of various proteins. They suggest that only a small fraction of mutations affect protein function adversely. For instance, a study of the bacteriophage T4 lysozyme generated more than 2000 random amino acid changes in the protein. Only 16% of them affected lysozyme function 1 . Other examples come from regulatory gene networks, such as the molecular network specifying fruit fly segments. Such networks may tolerate much quantitative variation in interactions among network genes 2-5 . Examples at the highest level of organization include macroscopic traits. Even substantial genetic variation -ultimately caused by mutations -may leave such traits unchanged. Take the vulva of the nematode worms Caenorhabditis elegans and Pristionchus pacificus 6 . These organisms shared a common ancestor 200-300 million years ago. Their vulvae are very similar, yet the genetic and cellular networks producing them have diverged greatly. For example, whereas in C. elegans one specific cell -the anchor cell -induces vulva development, multiple gonadal cells are responsible for this induction in P. pacificus 7 . Similarly, the same key signaling molecules, such as Wnt, may play a positive role in the network for vulval induction in C. elegans, but a negative role in P. pacificus 8,9 . In sum, mutational robustness is everywhere, from proteins to or...

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“…One may even replace the coding sequence of the Drosophila genes by the coding sequence of PAX3, a mouse ortholog of paired (Xue and Noll, 1996). Recently, it has also been shown in mice that the coding sequence of a Hox gene can replace its trans-paralog on another complex without consequences (Greer et al, 2000), even if the two genes have completely different sequences and functions in development.…”

Section: Promoters and Regulation Of Expressionmentioning

confidence: 99%

The diversity of subunit composition in nAChRs: Evolutionary origins, physiologic and pharmacologic consequences

2002

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Nicotinic acetylcholine receptors are made up of homologous subunits, which are encoded by a large multigene family. The wide number of receptor oligomers generated display variable pharmacological properties. One of the main questions underlying research in molecular pharmacology resides in the actual role of this diversity. It is generally assumed that the observed differences between the pharmacology of homologous receptors, for instance, the EC 50 for the endogenous agonist, or the kinetics of desensitization, bear some kind of physiologic relevance in vivo. Here we develop the quite challenging point of view that, at least within a given subfamily of nicotinic receptor subunits, the pharmacologic variability observed in vitro would not be directly relevant to the function of receptor proteins in vivo. In vivo responses are not expected to be sensitive to mild differences in affinities, and several examples of functional replacement of one subunit by another have been unravelled by knockout animals. The diversity of subunits might have been conserved through evolution primarily to account for the topologic diversity of subunit distribution patterns, at the cellular and subcellular levels. A quantitative variation of pharmacological properties would be tolerated within a physiologic envelope, as a consequence of a near-neutral genetic drift. Such a "gratuitous" pharmacologic diversity is nevertheless of practical interest for the design of drugs, which would specifically tackle particular receptor oligomers with a defined subunit composition among the multiple nicotinic receptors present in the organism.

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Maintenance of functional equivalence during paralogous Hox gene evolution

Cited by 236 publications

References 29 publications

Constructing the hindbrain: Insights from the zebrafish

Constructing the hindbrain: Insights from the zebrafish

Gene duplications, robustness and evolutionary innovations

The diversity of subunit composition in nAChRs: Evolutionary origins, physiologic and pharmacologic consequences

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