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español (castellano)

variation is not the deviation of the norm. variation is the norm.

 

why do we not all get sick, express disease, or respond to treatment in the same way?

why non-mutagenic chemicals can make us and our unexposed descendants susceptible to obesity?

why can salamanders regenerate their legs but neither frogs nor us can?

why animals have a lot more distinctive cell types than plants?

why colonies of identical individuals in the same environment are phenotypically heterogenous?

why same-sex dizygotic twins are less identical than same-sex monozygotic twins?

why is the number of species per taxa non-uniform?

why do species differ in their response to invasions, their susceptibility to become domesticated or good research model systems, their ability to form social structures, or their risk of becoming extinct?

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although these questions seem unrelated, they all exemplify the intrinsic ability biological systems have to vary. in spite of the far-reaching influence the study of the ultimate causes of biological variation might have, the knowledge on the mechanisms of biological variability is still very limited and disorganized.

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what do we have in common that makes us different?

 

the long-term goal of my research program is to contribute to a better understanding of the mechanisms of biological variability, i.e., the propensity of biological systems to vary. more specifically, my research program spans big data analysis, and theoretical and empirical projects to interrogate multiple levels of biological organization, e.g., molecules, genomes, nuclei, cells, tissues, individuals, populations, species, or communities, with three main goals:

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  1. to identify the ultimate units of biological variation, and the mechanisms and the properties of biological systems that directly participate in or bias the causation of such variation.

  2. to determine how biological variation is propagated through levels of organization resulting in phenotypic heterogeneity.

  3. to apply such knowledge:

    • to study the spatiotemporal dynamics of populations and communities.

    • to study the etiology and expression of human diseases.

    • to existing and new productive processes that use biological systems, from classical agriculture, to more modern biotechnology, bioengineering or synthetic biology.

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active areas of research within the logic framework for the causation of biological variation

which is the ultimate unit of variation?

genetic

non-genetic

which is the ultimate source of variation?

intrinsic

extrinsic

for example:

DNA methylation deamination

DNA break and its repair

DNA replication errors

for example:

position-effect variegation

transcription errors

translation errors

folding errors

for example:

radiation-induced DNA damage

for example:

phenotypic plasticity

biased genetic variation

geno-evo-regen

hjDNA-based capacitance model

trans-generational plasticity

chromatin compaction-based gene expression heterogeneity

no

yes

yes

no

is variation propagable through generations?

biased genetic variation. the study of biases in the distribution of genomic traits with regard to pertinent knowledge for the organization, expression, and evolution of genomes, and the nuclear dynamics of somatic and germ cells permits identifying potential mechanisms for the causation of genetic variation. in the past, i studied DNA sequence evolution with regard to chromosome location, gene order evolution with regard to potential functional constraints, and germ line subnuclear localization and DNA break repair preferences, and RNA-based gene duplications with regard to germ line subnuclear localization and DNA break repair preferences. 

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  1. Díaz-Castillo C. Females and males contribute in opposite ways to the evolution of gene order in Drosophila. PLoS One. 2013;8(5):e64491. 

  2. Díaz-Castillo C, Ranz JM. Nuclear chromosome dynamics in the Drosophila male germ line contribute to the nonrandom genomic distribution of retrogenes. Mol Biol Evol. 2012;29(9):2105-8.

  3. Díaz-Castillo C, Ranz JM. Recent progress on the identity and characterization of factors that shape gene organization during eukaryotic evolution. Fly (Austin). 2012;6(3):158-61.

  4. Díaz-Castillo C, Xia XQ, Ranz JM. Evaluation of the role of functional constraints on the integrity of an ultraconserved region in the genus Drosophila. PLoS Genet. 2012;8(2):e1002475.

  5. Ranz JM, Díaz-Castillo C, Petersen R. Conserved gene order at the nuclear periphery in Drosophila. Mol Biol Evol. 2012;29(1):13-6.

  6. Díaz-Castillo C, Golic KG. Evolution of gene sequence in response to chromosomal location. Genetics. 2007;177(1):359-74.

 

chromatin compaction-based gene expression heterogeneity. it is known that gene expression can be particularly noisy for genes located in highly compacted chromosome regions or heterochromatin. in the past, i studied gene expression heterogeneity dynamics with regard to those changes in chromatin organization naturally occurring between sexes or for dedifferentiating cells, and those driven by the exposure to environmental chemicals.

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  1. Chamorro-Garcia R*, Díaz-Castillo C*, Shoucri BM, Kach H, Leavitt R, Shioda T, Blumberg B. Ancestral perinatal obesogen exposure results in a transgenerational thrifty phenotype in mice. Nat Commun. 2017;8(1):2012. (*Equal contribution) 

  2. Díaz-Castillo C. Transcriptome dynamics along axolotl regenerative development are consistent with an extensive reduction in gene expression heterogeneity in dedifferentiated cells. PeerJ. 2017;5:e4004.

  3. Díaz-Castillo C. Theorizing about gene expression heterogeneity patterns after cell dedifferentiation and their potential value for regenerative engineering. In: Gardiner DM, editor. Regenerative engineering and developmental biology: principles and applications. CRC Press series in regenerative engineering. Boca Raton: Taylor & Francis/CRC Press; 2017. p. 351-60.

  4. Díaz-Castillo C. Evidence for a sexual dimorphism in gene expression noise in metazoan species. PeerJ. 2015;3:e750.

 

hjDNA-based capacitance model. although junk (j)DNA is a very controversial concept, it is unquestionable the involvement of individual jDNA elements in the causation of genetic variation. recently, i proposed the heterochromatin junk (hj)DNA-based capacitance model, which spans organization levels to explain how the inherent ability to vary shown by the jDNA in large repositories of heterochromatin promotes phenotypic heterogeneity, and how the ultimately hjDNA-based phenotypic heterogeneity permits natural populations thriving in variable environments and modulates genetic variation phenotypic exposure. since there are large differences in the genomic content of hjDNA between sexes in the same species and between species, i have used the hjDNA-based capacitance model to explain the sexual dimorphism for evolutionary trends for sex-biased gene expression, for gene expression and phenotypic heterogeneities, and for biological dispersal, and differences between species for genetic diversification driving speciation and cell specialization.

 

  1. Díaz-Castillo C. Regeneration: Why junk DNA might matter. PeerJ Preprints. 2018;6:e27255v1.

  2. Díaz-Castillo C. Same-sex twin pair phenotypic correlations are consistent with human Y chromosome promoting phenotypic heterogeneity. Evolutionary Biology. 2018;45(3):248-58.

  3. Díaz-Castillo C. Junk DNA and Genome Evolution. eLS. Chichester: John Wiley & Sons, Ltd; 2017. 

  4. Díaz-Castillo C. Junk DNA contribution to evolutionary capacitance can drive species dynamics. Evolutionary Biology. 2017;44(2):190-205.

  5. Díaz-Castillo C. Evidence for a sexual dimorphism in gene expression noise in metazoan species. PeerJ. 2015;3:e750.

 

geno-evo-regen (genomic determinants of the evolution of regeneration). in spite of being one of the oldest natural phenomena under study and its biomedical importance, what makes certain species able or unable to regenerate missing parts is largely a mystery. an intriguing observation that has not been yet conveniently pursued is that species with remarkable regenerative abilities such as salamanders or planarians tend to have genomes loaded with jDNA, whereas species for taxa with limited regenerative abilities such as birds or nematodes tend to have jDNA-poor genomes. recently, i used existing knowledge on the role of jDNA as genome evolution facilitator and its non-random chromosome and nuclear distributions to speculate about ways through which the variation in jDNA genomic content might end up enhancing or limiting regenerative responses.

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  1. Díaz-Castillo C. Regeneration: Why junk DNA might matter. PeerJ Preprints. 2018;6:e27255v1.

 

transgenerational plasticity. it is increasingly acknowledged that our phenotypes can reflect past environmental exposures of our ancestors, i.e., transgenerational plasticity. however, it is currently unclear how this happens mechanistically. in collaboration with the laboratory of Bruce Blumberg at UCI, i performed integrative analyses of adipose DNA methylome and transcriptome, and sperm chromatin accessibility with regard to nuclear architecture proxies for mice ancestrally exposed to the obesogen tributyltin (TBT). we proposed that great-great-grand-descendants of mice exposed to TBT are predisposed to obesity because of a transgenerationally propagable alteration of the nuclear architecture.

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  1. Díaz-Castillo C*, Chamorro-Garcia R*, Shoucri BM, Shioda T, Blumberg B. Mode of transgenerational propagation of chromatin organization alterations caused by the ancestral exposure to the obesogen tributyltin. (*Equal contribution; In preparation)

  2. Chamorro-Garcia R*, Díaz-Castillo C*, Shoucri BM, Kach H, Leavitt R, Shioda T, Blumberg B. Ancestral perinatal obesogen exposure results in a transgenerational thrifty phenotype in mice. Nat Commun. 2017;8(1):2012. (*Equal contribution)

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