Morphomics: The Genetics of Developmental Anatomy

Modularity in evolution: Some low-level questions

Altenberg, L. 2005 In. Callebaut, W., Rasskin-Gutman, D., eds. Modularity : Understanding the Development and Evolution of Complex Natural Systems, Ch. 5, pp. 1-32. Boston : MIT Press.

Abstract

Intuitive notions about the advantages of modularity for evolvability run into the problem of how we parse the organism into traits. In order to resolve the "question of multiplicity", there needs to be a way to get the human observer out of the way, and define modularity in terms of physical processes. I will offer two candidate ideas towards this resolution: 1-the dimensionality of phenotypic variation, and 2-the causal screening off of phenotypic variables by other phenotypic variables.  With this framework, the evolutionary advantages that have been attributed to modularity do not derive from modularity per se. Rather, they require that there be an "alignment" between the spaces of phenotypic variation, and the selection gradients that are available to the organism. Modularity may facilitate such alignment, but it is not sufficient; the appropriate phenotype-fitness map in conjunction with the genotype-phenotype map is also necessary for evolvability.

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Comment

This challenging 32-page theoretical paper introduces the term "morphomics." Altenberg takes on Plato’s problem of how to "carve nature at its joints" and advocates a search for underlying structure to explain the multiplicity of phenotypic variations seen in organisms. "Modularity" in genotype-phenotype interaction is one such way for this to occur because "if genetic changes tend to map to changes in a small number of phenotypic traits, then the genome can respond to selection on those traits alone," enhancing "evolvability." As environments changed through time directional selection acted on the modular genome to evolve into new ways of responding phenotypically, a process Altenberg terms "constructional selection." Altenberg’s model provides a theoretical basis for understanding homeotic gene function, segmental anatomy, and embryology within a framework of evolutionary biology.

Gene regulatory networks in the evolution and development of the heart.

Olson, EN, 2006. Science 313 :1922-1927.

Abstract

The heart, an ancient organ and the first to form and function during embryogenesis, evolved by the addition of new structures and functions to a primitive pump. Heart development is controlled by an evolutionary conserved network of transcription factors that connect signaling pathways with genes for muscle growth, patterning, and contractility. During evolution, this ancestral gene network was expanded through gene duplication and co-option of additional networks. Mutations in components of the cardiac gene network cause congenital heart disease, the most common human birth defect. The consequences of such mutations reveal the logic of organogenesis and the evolutionary origins of morphological complexity.

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Comment

This paper provides an “evo-devo” overview of heart development with a discussion of many of the important genes and gene networks involved in heart embryogenesis and heart defects.

Bridging the gap between anatomy and molecular genetics for an improved understanding of congenital heart disease.

Reamon-Buettner, S., K. Spanel-Borowski, J. Borlak 2006 Annals of Anatomy188 :213-220.

Abstract

Birth defects are the leading cause of infant mortality and malformations in congenital heart disease (CHD) and are among the most prevalent and fatal of birth defects. Yet the molecular mechanisms leading to CHD are complex and the causes of the cardiac malformations observed in humans are still unclear. In recent years, the pivotal role of certain transcription factors in heart development has been demonstrated, and gene targeting of cardiac-specific transcription factor genes in animal models has provided valuable insights into heart anomalies. Nonetheless results in these models can be species specific, and in humans, germline mutations in transcription factor genes can only account for some cases of CHD. Furthermore, most patients do not have family history of CHD. There is, therefore, a need for a better understanding of the mechanisms in both normal cardiac development and the formation of malformations. The combining of expertise in cardiac anatomy, pathology, and molecular genetics is essential to adequately comprehend developmental abnormalities associated with CHD. To help elucidate genetic alterations in affected tissues of malformed hearts, we carried out genetic analysis of cardiac-specific transcription factor genes from the Leipzig collection of formalin-fixed malformed hearts. Working with this morphologically well-characterized archival material not only provided valuable genetic information associated with disease, but enabled us to put forward a hypothesis of somatic mutations as a novel molecular cause of CHD. Knowledge of cause and disease mechanism may allow intervention that could modify the degree of cardiac malformations or development of new approaches for prevention of CHD.

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Comment

A useful summary of the major genes known to mediate heart development. The authors find that somatic mutations characterize a sample of preserved malformed hearts and posit this mechanism to account in part for congenital heart disease.