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A solution to Darwin's 'mystery of the mysteries' emerges from the dark matter of the genome
October 27, 2009SEATTLE - Biological species are often defined on the basis of reproductive isolation. Ever since Darwin pointed out his difficulty in explaining why crosses between two species often yield sterile or inviable progeny (for instance, mules emerging from a cross between a horse and a donkey), biologists have struggled with this question. New research into this field by basic scientists at Fred Hutchinson Cancer Research Center, published online Oct. 22 in Science Express, suggests that the solution to this problem lies within the "dark matter of the genome": heterochromatin, a tightly packed, gene-poor compartment of DNA found within the genomes of all nucleated cells.
"Speciation is one of the most fascinating, unsolved problems in biology," said Harmit Malik, Ph.D., an associate member of the Hutchinson Center's Basic Sciences Division and corresponding author of the paper.
Malik and first author Joshua Bayes, Ph.D., a former graduate student in the Malik lab, focused on understanding the cellular function of a particular fruit fly (Drosophila) gene dubbed Odysseus. The gene is so named because of its ability to cause havoc and male sterility when introduced into the genome of another species. Odysseus is a gene that is derived from a transcription factor, and it was long believed to be a protein that turned on expression of other genes in Drosophila testis.
Odysseus also had been previously shown to rapidly evolve in its DNA-binding domain. Based on this observation, Bayes and Malik reasoned that Odysseus must interact with some rapidly evolving DNA in the genome. They tested the hypothesis, first proposed by Malik and Hutchinson Center colleague Steven Henikoff, Ph.D., that such hybrid-sterility proteins may bind repetitive satellite DNA in heterochromatin. Such repeats are believed to evolve rapidly due to an "arms-race" for preferential transmission during the process of forming an egg, whereby only one of four chromosomes is non-randomly chosen to be included into the egg.
Consistent with this hypothesis, Bayes found that Odysseus proteins localize to heterochromatic DNA found next to centromeres and on gene-poor chromosomes, which leads to their decondensation. Dramatically, the hybrid-sterility-associated Odysseus from one species showed additional localization to the Y chromosome of the other species. Through experiments in cell lines and transgenic flies, Bayes further showed that Odysseus localization has rapidly evolved during recent evolution, evidence of the "arms-race" that drives rapid evolution of satellite DNA repeats. Altered expression and localization has profoundly deleterious consequences for the process of sperm formation, a process that remains a mystery and is under active study in the Malik lab.
The finding that rapidly evolving heterochromatin may underlie this phenomenon also ties in with other work in Malik's lab that explores how "mismatches" originating from rapid evolution of DNA and proteins could lead to chromosome segregation defects and aneuploidy events that are sometimes precursors in transitions to cancer.
Fred Hutchinson Cancer Research Center
Odysseus also had been previously shown to rapidly evolve in its DNA-binding domain. Based on this observation, Bayes and Malik reasoned that Odysseus must interact with some rapidly evolving DNA in the genome. They tested the hypothesis, first proposed by Malik and Hutchinson Center colleague Steven Henikoff, Ph.D., that such hybrid-sterility proteins may bind repetitive satellite DNA in heterochromatin. Such repeats are believed to evolve rapidly due to an "arms-race" for preferential transmission during the process of forming an egg, whereby only one of four chromosomes is non-randomly chosen to be included into the egg.
Consistent with this hypothesis, Bayes found that Odysseus proteins localize to heterochromatic DNA found next to centromeres and on gene-poor chromosomes, which leads to their decondensation. Dramatically, the hybrid-sterility-associated Odysseus from one species showed additional localization to the Y chromosome of the other species. Through experiments in cell lines and transgenic flies, Bayes further showed that Odysseus localization has rapidly evolved during recent evolution, evidence of the "arms-race" that drives rapid evolution of satellite DNA repeats. Altered expression and localization has profoundly deleterious consequences for the process of sperm formation, a process that remains a mystery and is under active study in the Malik lab.
The finding that rapidly evolving heterochromatin may underlie this phenomenon also ties in with other work in Malik's lab that explores how "mismatches" originating from rapid evolution of DNA and proteins could lead to chromosome segregation defects and aneuploidy events that are sometimes precursors in transitions to cancer.
Fred Hutchinson Cancer Research Center
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Heterochromatin: Webster's Timeline History, 1952 - 2007 by Icon Group International (Author) Webster's bibliographic and event-based timelines are comprehensive in scope, covering virtually all topics, geographic locations and people. They do so from a linguistic point of view, and in the case of this book, the focus is on "Heterochromatin," including when used in literature (e.g. all authors that might have Heterochromatin in their name). As such, this book represents the largest compilation of timeline events associated with Heterochromatin when it is used in proper noun form. Webster's timelines cover bibliographic citations, patented inventions, as well as non-conventional and alternative meanings which capture ambiguities in usage. These furthermore cover all parts of speech (possessive, institutional usage, geographic usage) and contexts, including pop culture, the arts,... |
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CHROMOSOMES OF ANTELOPE SQUIRRELS (GENUS AMMOSPERMOPHILUS): A SYSTEMATIC BANDING ANALYSIS OF FOUR SPECIES WITH UNUSUAL CONSTITUTIVE HETEROCHROMATIN. by J. & J. Mazrimas Mascarello (Author), Plates (Illustrator) | |
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Silencing, Heterochromatin and DNA Double Strand Break Repair by Kevin D. Mills (Author) The field of DNA repair is vast and advancing rapidly. Silencing, Heterochromatin and DNA Double Strand Break Repair probes the relationship of DNA break repair and silent heterochromatin, using budding yeast as a model. The primary research presented in this book represents some of the most important work in this new field of inquiry. |
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Heterochromatin: Molecular and Structural Aspects by Ram Sagar Verma (Editor) Ram Verma has assembled ten distinguished contributors to survey what is currently known about the relationship of the structure of DNA to its role in the function and expression of genes. The crucial role of heterochromatin in the organization of chromosomes is thoroughly explored in this resulting landmark edited volume. Cytogeneticists and other geneticists, molecular biologists, cytologists, biochemists and their advanced students will also find this an invaluable reference source. |
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RNA Interference (Current Topics in Microbiology and Immunology) by Patrick J. Paddison (Author), Patrick J. Paddison (Editor), Peter K. Vogt (Editor) In the last few years the major effect that RNAi has had in invertebrate systems like C.elegans and drosophila is beginning to take hold in mammalian systems through both single gene knockdown experiments and genome-scale screens. In the next decade, there will no doubt be both notable successes and failures as we attempt to apply this genetic tool to various biological problems for the first time in academia and industry. Through the introduction of RNAi, mammalian systems have finally gained admittance to the pantheon of model genetic systems. |
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Protein Complexes that Modify Chromatin. Current Topics in Microbiology and Immunology, No. 274 by Jerry L. Workman (Editor) This book provides timely reviews of several protein complexes that regulate gene expression and chromatin dynamics. Examples of such complexes include: nucleosome assembly complexes, ATP-dependent chromatin remodeling complexes, histone acetyltransferase complexes, histone deacetylase complexes, heterochromatin complexes, SMC complexes and transcription elongation complexes. These chapters will bring experts in the field up to date on several aspects of chromosome biology and will provide an exiting introduction to the field for new chromatin researchers. |
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Can variants in the constitutive heterochromatin of human chromosomes be detected consistently? by Michelle F Browner (Author) | |
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Polytene chromosomes, heterochromatin, and position effect variegation (Advances in genetics) by I. F Zhimulëv (Author) |
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