Publications (7)45.63 Total impact
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Article: The evolution of MDM2 family genes.
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ABSTRACT: MDM2 and MDM4 are proto-oncoproteins that bind to and inhibit members of the p53 protein family, p53, p73 and possibly p63. p53 is a mammalian tumor suppressor and p63 and p73 are critical for development. With the sequencing of genomes from multiple organisms there is mounting evidence for a consensus scenario of p53 gene family evolution. A single p53/p63/p73 gene is in invertebrates and required for maintenance of germline DNA. Gene duplication occurred in an ancestor in common with cartilaginous fishes, giving rise to a separate p53 gene and at least one ancestral p63/p73 gene. In bony vertebrates, all three p53 gene family paralogs, p53, p63, and p73 are distinct genes. This raises the question of how MDM2 and MDM4 genes evolved. We show evidence that MDM2 and MDM4 arose from a gene duplication event prior to the emergence of bony vertebrates more than 440 millionyears ago. Comparative genome studies indicate that invertebrate organisms have only one MDM homolog. In jawed vertebrates, the p53-binding domains of MDM2 and MDM4 proteins evolved at a high rate, approaching the evolution rate of the MDM2-binding domain of p53. However, the MDM2-binding domain of p73 exhibits markedly stronger conservation suggesting novel p53-independent functions. The most conserved domain within all MDM2 family members is the RING domain of the MDM2 ortholog which is responsible for ubiquitination of p53 and heterodimerization with MDM4. We suggest a model where oligomerization is an ancient function of MDM and ubiquitination activity was acquired later near the MDM gene duplication event coinciding with the time of the emergence of p53 as a distinct gene.Gene 10/2011; 486(1-2):23-30. · 2.34 Impact Factor -
Article: Sequences from ancestral single-stranded DNA viruses in vertebrate genomes: the parvoviridae and circoviridae are more than 40 to 50 million years old.
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ABSTRACT: Vertebrate genomic assemblies were analyzed for endogenous sequences related to any known viruses with single-stranded DNA genomes. Numerous high-confidence examples related to the Circoviridae and two genera in the family Parvoviridae, the parvoviruses and dependoviruses, were found and were broadly distributed among 31 of the 49 vertebrate species tested. Our analyses indicate that the ages of both virus families may exceed 40 to 50 million years. Shared features of the replication strategies of these viruses may explain the high incidence of the integrations.Journal of Virology 12/2010; 84(23):12458-62. · 5.40 Impact Factor -
Article: The origins and evolution of the p53 family of genes.
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ABSTRACT: A common ancestor to the three p53 family members of human genes p53, p63, and p73 is first detected in the evolution of modern-day sea anemones, in which both structurally and functionally it acts to protect the germ line from genomic instabilities in response to stresses. This p63/p73 common ancestor gene is found in almost all invertebrates and first duplicates to produce a p53 gene and a p63/p73 ancestor in cartilaginous fish. Bony fish contain all three genes, p53, p63, and p73, and the functions of these three transcription factors diversify in the higher vertebrates. Thus, this gene family has preserved its structural features and functional activities for over one billion years of evolution.Cold Spring Harbor perspectives in biology 06/2010; 2(6):a001198. · 9.40 Impact Factor -
Article: Unexpected inheritance: multiple integrations of ancient bornavirus and ebolavirus/marburgvirus sequences in vertebrate genomes.
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ABSTRACT: Vertebrate genomes contain numerous copies of retroviral sequences, acquired over the course of evolution. Until recently they were thought to be the only type of RNA viruses to be so represented, because integration of a DNA copy of their genome is required for their replication. In this study, an extensive sequence comparison was conducted in which 5,666 viral genes from all known non-retroviral families with single-stranded RNA genomes were matched against the germline genomes of 48 vertebrate species, to determine if such viruses could also contribute to the vertebrate genetic heritage. In 19 of the tested vertebrate species, we discovered as many as 80 high-confidence examples of genomic DNA sequences that appear to be derived, as long ago as 40 million years, from ancestral members of 4 currently circulating virus families with single strand RNA genomes. Surprisingly, almost all of the sequences are related to only two families in the Order Mononegavirales: the Bornaviruses and the Filoviruses, which cause lethal neurological disease and hemorrhagic fevers, respectively. Based on signature landmarks some, and perhaps all, of the endogenous virus-like DNA sequences appear to be LINE element-facilitated integrations derived from viral mRNAs. The integrations represent genes that encode viral nucleocapsid, RNA-dependent-RNA-polymerase, matrix and, possibly, glycoproteins. Integrations are generally limited to one or very few copies of a related viral gene per species, suggesting that once the initial germline integration was obtained (or selected), later integrations failed or provided little advantage to the host. The conservation of relatively long open reading frames for several of the endogenous sequences, the virus-like protein regions represented, and a potential correlation between their presence and a species' resistance to the diseases caused by these pathogens, are consistent with the notion that their products provide some important biological advantage to the species. In addition, the viruses could also benefit, as some resistant species (e.g. bats) may serve as natural reservoirs for their persistence and transmission. Given the stringent limitations imposed in this informatics search, the examples described here should be considered a low estimate of the number of such integration events that have persisted over evolutionary time scales. Clearly, the sources of genetic information in vertebrate genomes are much more diverse than previously suspected.PLoS Pathogens 01/2010; 6(7):e1001030. · 9.13 Impact Factor -
Article: One billion years of p53/p63/p73 evolution.
Proceedings of the National Academy of Sciences 10/2009; 106(42):17609-10. · 9.68 Impact Factor -
Article: Periodic Pattern Formation in Evaporating Drops
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ABSTRACT: Solute deposits from evaporating drops with pinned contact line are usually concentrated near the contact line. The stain, or pattern, left on the substrate then consists of a single ring, commonly known as a coffee ring. Here we report on a variation of this phenomenon when periodic patterns emerge. We attribute these to phase transitions in certain solutes as solute concentration increases. Examples may include dissolved to crystalline transition in salt or order-disorder transition in liquid crystals. Activated nature of the phase transitions, along with the newly imposed boundaries between phases, may then invert solute density profile and lead to periodic deposits. Hereby we develop a general theoretical model and report on experimental observations on salt in water.01/2007; -
Article: Electrostatic origin of the genome packing in viruses.
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ABSTRACT: Many ssRNA/ssDNA viruses bind their genome by highly basic semiflexible peptide arms of capsid proteins. Here, we show that nonspecific electrostatic interactions control both the length of the genome and genome conformations. Analysis of available experimental data shows that the genome length is linear in the net charge on the capsid peptide arms, irrespective of the actual amino acid sequence, with a proportionality coefficient of 1.61 +/- 0.03. This ratio is conserved across all ssRNA/ssDNA viruses with highly basic peptide arms, and is different from the one-to-one charge balance expected of specific binding. Genomic nucleotides are predicted to occupy a radially symmetric spherical shell detached from the viral capsid, in agreement with experimental data.Proceedings of the National Academy of Sciences 12/2006; 103(46):17174-8. · 9.68 Impact Factor
Top co-authors
Top Journals
Institutions
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2011
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California State University, Los Angeles
- Department of Chemistry and Biochemistry
Los Angeles, CA, USA
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2009–2010
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Institute for Advanced Study
Princeton, NJ, USA
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2006
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University of Massachusetts Amherst
- Department of Polymer Science and Engineering
Amherst Center, MA, USA
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