Institute of Molecular
Evolutionary Genetics











Spring 2008


Previous IMEG Seminars and Abstracts:

Fall 2013

Spring 2013

Fall 2012


Spring 2012

Fall 2011

Fall 2010


Spring 2010
Fall 2009

Spring 2009

Fall 2008

Spring 2008

Fall 2007
Spring 2007
Fall 2006

Spring 2006
Fall 2005
Spring 2005

Fall 2004

Spring 2004

Fall 2003

Spring 2003
Fall 2002




Speaker: Dr. Ilana Baums - Department of Biology

Title: Comparative genomics in non-model organisms: the role of dispersal in the ecology and evolution of reef corals 


Abstract: Our view of the role of dispersal in the ecology and evolution of reef corals has changed dramatically over the last decade due in part to advances in molecular genetics. It was previously thought that dispersal of floating propagules (larvae) via ocean currents would routinely connect even distant populations (1000s of km). New molecular markers contradict this notion: most ecologically relevant dispersal occurs over shorter distances. In the Caribbean, bio-physical models emphasize the importance of the timing of larval release with respect to the occurrence of transient oceanographic features in determining scales of larval dispersal. We identified one such oceanographic feature, an eddy that develops over the summer months in the Mona Passage as a potential barrier to larval dispersal. Though narrow (113 km wide), the Mona Passage divides Caribbean coral populations into an eastern and western province (Baums et al.2005). Within each province, patterns of fragmentation (a form of asexual reproduction) indicate that certain genets may outcompete others locally (<< 1km) and led us to hypothesize that fine-scale site-adaptation exists in these corals (Baums et al. 2006). The biology of the animal precludes the use of traditional transplantation experiments and quantitative genetic methods to further test this hypothesis. Instead, we are taking a comparative transcriptome approach (Toth et al. 2007).  Challenges include frequent hybridization among coral species and a dearth of genomic data for related organisms (but see Putnam et al. 2007). The finding of site-adaptation in corals with planktonic larvae would have important consequences for the restoration of coral reefs, indicating that careful matching of propagules to transplantation sites is necessary.

References:Baums IB, Miller MW, Hellberg ME (2005) Regionally isolated populations of an imperiled Caribbean coral, Acropora palmata. Molecular Ecology 14, 1377-1390.
Baums IB, Miller MW, Hellberg ME (2006) Geographic variation in clonal structure in a reef building Caribbean coral, Acropora palmata. Ecological Monographs 76, 503-519.
Putnam NH, Srivastava M, Hellsten U, et al. (2007) Sea anemone genome reveals ancestral eumetazoan gene repertoire and genomic organization. Science 317, 86-94.
Toth AL, Varala K, Newman TC, et al. (2007) Wasp Gene Expression Supports an
Evolutionary Link Between Maternal Behavior and Eusociality. Science, 1146647.


Speaker: Xiaofan Zhou - Department of Biology

Title: Phylogenetic Analyses of Two Histone Demethylase Gene Families

Histone methylation has been recognized as an important way to regulate chromatin structure and gene expression in eukaryotes for a long time. However, not until the identification of two families of histone demethylase, the KDM1 (previously known as LSD1) and JmjC-domain containing proteins in recent years, this modification was found to be reversible. These two families of proteins have different functional domains and different substrate specificities. Whereas increasing number of new members are proved to have histone demethylase activity, only limited is known about the origin and evolution history of these two families. In this study, we collected KDM1-like and JmjC-domain containing proteins in both eukaryotes and prokaryotes, and performed systematic phylogenetic analyses. Our results indicate two distinct patterns of evolution; the KDM1-like histone demethylase originated through acquiring a SWIRM domain in the common ancestor of eukaryotes, and then experienced limited expansion in plants while maintained two copies in most animals except for insects which lost one. The JmjC-domain containing proteins can be divided into more than ten subfamilies, and each has different domain architecture and substrate specificity. At least seven subfamilies have already existed before the divergence of eukaryotes, and then most subfamilies were expanded through gene duplication. Our work also provides reference for the further functional studies on histone demethylase.

References: Shi Y, Whetstine JR. (2007). “Dynamic regulation of histone lysine methylation by demethylases.” Mol Cell. 25(1):1-14.

Klose RJ, Kallin EM, Zhang Y (2006). “JmjC-domain-containing proteins and histone demethylation.” Nat Rev Genet. 7(9):715-27.


Speaker: Dr. Hiroki Goto, Lei Peng, and Kateryna D. Makova - Department of Biology and Center for Comparative Genomics and Bioinformatics

Title: Evolution of X-degenerate Y chromosome genes in greater apes: Conservation of gene content in human and gorilla, but not chimpanzee

Abstract: Compared with the X chromosome, the human Y chromosome is considerably diminished in size and has lost most of its functional genes, leading to predictions that it might become extinct within only a few million years. Although several population genetic models explaining Y chromosome degeneration have been proposed, their relative importance for the evolution of this chromosome in apes remains puzzling. Interestingly, for the X-degenerate region on the Y chromosome, human retained all 16 genes, while chimpanzee lost 4 of the 16 genes since the divergence of the two species.  To uncover the evolutionary forces governing ape Y chromosome degeneration, we determined the complete sequences of the coding exons and their splice sites for 16 gorilla Y chromosome genes located in the X-degenerate region. We discovered that all studied reading frames and splice sites were intact and thus, this genomic region experienced no gene loss in the gorilla lineage after its divergence from the human-chimpanzee-gorilla common ancestor. Higher nucleotide divergence was observed in the chimpanzee than human lineage and this difference was more pronounced for the genes with disruptive mutations, suggesting a lack of functional constraints for these genes in chimpanzee. Surprisingly, our results indicate that the human and gorilla orthologs of the genes disrupted in chimpanzee evolve under relaxed functional constraints and might not be essential for all apes. Taking mating patterns and effective population sizes of human, chimpanzee, and gorilla into account, we concluded that genetic hitchhiking associated with positive selection due to sperm competition might explain a rapid decline in the Y chromosome gene number in chimpanzee. Since we found no evidence of positive selection acting on the X-degenerate genes, such selection likely targets other genes on the chimpanzee Y chromosome.

References: Hughes JF et al. (2005) Conservation of Y-linked genes during human evolution revealed by comparative sequencing in chimpanzee. Nature 437:100-103.


Speaker: Jill Duarte - Department of Biology

Title: Phylogenetic Utility of Conserved Single Copy Nuclear Genes in Flowering Plants

Given the prevalence of gene duplication in flowering plants, the presence of approximately 600 widely conserved single copy genes in flowering plants is a surprising observation.   In this talk, I will focus on one aspect of our current research on these fascinating components of the plant genome, namely, their potential utility as protein-coding nuclear genes that can be used as novel phylogenetic markers. Using the PlantTribes database (, we have identified proteins that are single copy in two or more genomes.  To investigate the phylogenetic utility of these genes, we have selected approximately twenty genes that have good representation in EST databases.  To study how they perform as phylogenetic markers, we have used them in a series of phylogenetic analyses at various taxanomic levels: Brassicaceae, basal angiosperms, and seed plants.  The results from these studies indicates that although duplications of these genes can persist in some lineages, a single expressed copy is typical and these genes contain a sufficient amount of phylogenetic signal, in spite of typically short coding sequences.

Sang, T. 2002. Utility of low-copy nuclear gene sequences in plant phylogenetics. Critical Reviews in Biochemistry and Molecular Biology 37:121-147.

Small, R. L., R. C. Cronn, and J. F. Wendel. 2004. Use of nuclear genes for phylogeny reconstruction in plants. Australian Systematic Botany 17:145-170.

Soltis, D. E., and P. S. Soltis. 1998. Choosing an approach and an appropriate gene for phylogenetic analysis. Pp. 1-42 in D. E. Soltis, P. S. Soltis, and J. J. Doyle, eds. Molecular systematics of   Plants II. DNA Sequencing. Kluwer Academic Publishers, Boston.

Strand, A. E., J. Leebens-Mack, and B. G. Milligan. 1997. Nuclear DNA-based markers for plant evolutionary biology. Molecular Ecology 6:113-118.

Wall, P. K., Leebens-Mack, J., Muller, K. F., Field, D., Altman, N. S., and dePamphilis, C. W. 2008. PlantTribes: a gene and gene family resource for comparative genomics in plants. Nucleic Acids  Research, 36: D970-6.


Speaker: Dr. Beth Shapiro - Department of Biology

Title: Investigating extinction using ancient DNA


Abstract: The recent advent of ancient DNA (aDNA) techniques makes it possible to directly observe evolutionary and population genetic changes in species and communities through time. DNA extracted from hair, teeth and bones of animal remains, as well as directly from soil cores, can be used to reconstruct changes in population size and structure potentially as far back as the most recent common ancestor of the sampled sequences. While significant limitations to the technique remain, for example the potential for DNA damage and modern contamination to interfere with experiments and confound phylogenetic analysis, and the almost complete reliance on mitochondrial DNA markers due to the low-copy number of nuclear DNA, aDNA has shown significant promise as a method for examining molecular evolutionary processes in populations. I will discuss the application of aDNA techniques to investigating the cause of the megafaunal mass extinction that occurred at the Pleistocene/ Holocene boundary (ca 10 thousand years ago; ka BP). I will describe the use of maximum likelihood and Bayesian techniques for reconstructing population history for five large mammals that were once abundant in the Siberian and North American arctic: bison (Bison priscus), horses (Equus caballus), cave lions (Panthera spelea), brown bears (Ursus arctos) and mammoths (Mammuthus primigenius). Our results indicate that climate change, rather than over-hunting by humans, was the driving force behind the extinction events, with significant losses of genetic diversity in all of these species beginning just prior to the onset of glacial conditions, ca. 25-30 ka BP. We also demonstrate multiple, distinct periods of population turnover over the most recent 60 ka BP, suggesting repeated periods of local extinctions and replacements, large-scale migration between regions and transient barriers to gene flow. These results demonstrate the power of serially sampled data from measurably evolving populations to uncover significantly different demographic scenarios than it is possible to observe with modern data alone.


References: Barnes I, Shapiro B, Kuznetsova T, Sher A, Guthrie D, Lister A, Thomas MG. Genetic structure and extinction of the woolly mammoth Mammuthus primigenius (Blum.). Current Biology 17: 1072-1075 (2007).

Drummond AJ, Pybus OG, Shapiro B, Rambaut A. Bayesian coalescent inference of past population dynamics from molecular sequences. Molecular Biology and Evolution 22: 1185-1192 (2005).

Shapiro B, Drummond AJ, Rambaut A, Wilson MC, Matheus P, Sher AV, Pybus OG, Gilbert MTP, Barnes I, Binladen J, Willerslev E, Hansen A, Baryshnikov GF, Burns JA, Davydov S, Driver JC, Froese D, Harington CR, Keddie G, Kosintsev P, Kunz ML, Martin LD, Stephenson RO, Storer J, Tedford R, Zimov S, Cooper A. Rise and fall of the Beringian steppe bison. Science 306: 1561-1565 (2004).

Hofreiter M, Serre D, Poinar HN, Kuch M, Paabo S. Ancient DNA. Nature Reviews Genetics 2: 353-359.


Speaker: Dr. Steve Schaeffer - Department of Biology

Title: Chromosomal Rearrangements inferred from the 12 Drosophila Genomes Project

Abstract: Comparative genomics offers an unprecedented opportunity to examine how gene order evolves on chromosomes and its significance.  The recent completion of 12 Drosophila genomes has been used to develop computational methods for assembling eukaryotic genomes and to test these scaffold assemblies using the polytene chromosomal maps.  I will discuss how the assembly scaffolds from the 11 non-D. melanogaster genomes were anchored to the polytene maps with computational and physical mapping approaches.  These maps were a critical first step in the examination of gene order evolution.

     Gene order data among the divergent Drosophila species was analyzed with a variety of graphical and statistical approaches.  Comparison of syntenic blocks across this large genomic dataset confirms that genetic elements are largely (95%) localized to the same Muller element across genus Drosophila species and paracentric inversions serve as the dominant mechanism for shuffling the order of genes along a chromosome. Gene order scrambling between species is in accordance with the estimated evolutionary distances between them and we find it to approximate an exponential process over time (linear with alternate divergence rates). Our results provide estimated chromosomal evolution rates across this set of species based on whole-genome synteny analysis, which are found to be higher than those previously reported. Analysis of conserved syntenic blocks across these genomes suggests clustering based on various criteria, including function and various patterns of embryonic expression correlation in D. melanogaster. On the other hand, an analysis of the disruption of syntenic blocks between species allowed the identification of fixed inversion breakpoints and estimates of breakpoint re-usage.

References: Drosophila 12 Genomes Consortium. 2007. Evolution of genes and genomes on the Drosophila phylogeny. Nature 450:203-218.


Speaker: Dr. George Zhang - Department of Ecology and Evolutionary Biology, University of Michigan

Title: Metabolic network analysis for understanding evolution

"I plan to present the results from two studies that both utilize the flux balance analysis (FBA) of metabolic networks.  The first is about functional redundancy of metabolic reactions and its evolutionary maintenance.  The second is about the biological basis of epistasis.  The two studies have not been published, but below are brief summaries. "
On metabolic redundancy

     Cellular life is a highly redundant complex system, yet the evolutionary maintenance of the redundancy remains unexplained.  We infer that 37-47% of metabolic reactions in E. coli and yeast can be individually removed without blocking the production of any biomass component under any nutritional condition.  However, the majority of these redundant reactions are preserved, because they have differential maximal efficiencies at different conditions or their loss causes a fitness reduction that can only be recovered via evolution.  The remaining redundancies are attributable to pleiotropic effects or recent horizontal gene transfers.  Thus, redundant reactions need not be kept as backups and the genetic robustness of metabolic networks is likely an evolutionary byproduct.

 On epistasis

     Epistasis, a term coined by Bateson nearly 100 years ago, refers to the phenomenon that the effect of a gene on a trait is masked or enhanced by one or more other genes.  Fisher soon extended the concept to mean non-independent or non-multiplicative effects of genes.  The direction, magnitude, and prevalence of epistasis is important for understanding gene function and interaction, speciation, evolution of sex and recombination, evolution of ploidy, mutation load, genetic buffering, human disease, and drug-drug interaction.  Although high-throughput epistasis data from model organisms are being generated and used to construct genetic networks, to what extent epistasis reflects functional intimacy of involved genes is unclear.  We here address this question in the Escherichia coli metabolic network, where both epistasis and functional relationships of biochemical reactions can be evaluated through systemic analysis.  We found that negative or synergistic epistasis in fitness occurs mainly between nonessential reactions with overlapping functions, whereas positive or antagonistic epistasis usually involves essential reactions, is highly abundant, and surprisingly, often occurs between reactions without overlapping functions.  These observations, together with theoretical considerations of their causes, require the distinction of the concept of genetic interaction from non-multiplicative gene effects and necessitate reconsideration of evolutionary theories that depend on prevalent negative epistasis."

Price ND, Reed JL, Palsson BŘ. Nat Rev Microbiol. 2004 Nov; 2(11):886-97. Genome-scale models of microbial cells: evaluating the consequences of constraints.



Speaker: Solny Adalsteinsson - Department of Biology

Title: Molecular Phylogenetics and Biogeography of the Snake Family Leptotyphlopidae

The threadsnakes (Leptotyphlopidae) comprise one of the last major groups of terrestrial vertebrates for which essentially nothing is known of its evolutionary history, from molecules or morphology.  They include the world’s smallest snakes and occur mainly in South America, Africa, and southwest Asia. The family consists of two genera and 104 species.  These are burrowing snakes that have no fossil record and greatly reduced scale features, making even morphological analysis difficult. Most are about the diameter and shape of a spaghetti noodle and many of the species are known from only one or a few specimens.  We were fortunate to assemble a relatively large collection of tissue samples for molecular analysis (mitochondrial and nuclear gene sequences), and the results will be presented.  They reveal some unexpected geographic patterns and a surprisingly large number of cryptic species.


Reference: Vidal, N., A. Azvolinsky, C. Cruaud, and S. B. Hedges. 2008. Origin of tropical American burrowing reptiles by transatlantic rafting. Biology Letters 4:115-118.








Speaker: Melissa Wilson - Department of Biology
Title: Evolution and Survival on Eutherian Sex Chromosomes


Abstract: Since the two eutherian sex chromosomes diverged from an ancestral autosomal pair, the X has remained relatively gene-rich, while the Y lost most of its genes through the accumulation of deleterious mutations in nonrecombining regions. Presently, it is unclear when the sex chromosomes acquired their unique evolutionary rates, what is distinctive about the genes remaining on the Y chromosome, and whether X-Y gene divergence paralleled that of paralogs located on autosomes. To tackle these questions, here we juxtaposed the evolution of nine X and Y homologous genes (gametologs) in human and mouse with their autosomal orthologs in opossum and platypus. We discovered that genes on the X and Y acquired distinct evolutionary rates immediately following the suppression of recombination between the two sex chromosomes. The Y-linked genes evolved at higher rates, while the X-linked genes maintained the lower evolutionary rates of the ancestral autosomal genes. We further established that, surprisingly, the surviving gametologs had less radical and fewer overall amino acid changes than did autosomal paralogs. Curiously, in contrast to expectations, most Y gametologs evolved under stronger purifying selection than the quickly evolving copies of autosomal duplicate pairs. Finally, after evaluating expression and functional laboratory experiments, we concluded that, to be retained on both the X and the Y, gametologs evolved unique mRNA and protein expression patterns as well as separate functions.


Reference: Wyckoff, G. J., Li, J., and C. Wu. 2002. Molecular evolution of functional genes on the mammalian Y chromosome. Mol. Biol. Evol. 19(9)1633-1636.


Speaker: Yan Zhang - Department of Biology

Title: Striking convergence of plastid genome in independent nonphotosynthetic lineages


Abstract: Parasitic plants are valuable models for studying genes and genome evolution. Under relaxed functional constraint, the plastid genomes of some parasitic plants have undergone great reduction in gene content and exhibited accelerated rates of evolution for the remaining genes. For example, the fully sequenced plastid genome of the nonphotosynthetic plant Epifagus virginiana (Orobanchaceae) displays extreme genome reduction; it lacks functional copies of all photosynthetic and ndh genes, all four RNA polymerase genes, nearly half of the tRNA genes, and one third of the ribosomal protein genes. Accelerated evolution is observed in Epifagus. Recent complete sequences of the plastid genome of Cuscuta, an independent lineage of parasitic plant, reveal plastid genomes distinctly different from Epifagus, but species of this group retain a minimal photosynthetic ability.  To understand whether genome evolution is similar in other independent lineages of nonphotosynthetic plants, the plastid genome of Pholisma arenarium (Lennoaceae/Boraginaceae) has been fully sequenced.. The plastid genomes of Ehretia acuminata (Boraginaceae), a photosynthetic relative of Pholisma, and Mimulus guttatus (Phrymaceae), a photosynthetic relative of Epifagus, were also sequenced. The plastid genome of Pholisma shows a pattern of gene loss that is strikingly similar to that observed in Epifagus. All of the photosynthetic genes (with the notable exception of rbcL and psaI) and ndh genes are lost, as are the RNA polymerase genes and some components of the translation apparatus. The gene losses in Pholisma are a perfect subset of those observed in Epifagus, and the remaining genes are also evolving at accelerated rates, but not as accelerated as Epifagus. The results indicate parallel evolution of the two independent lineages of nonphotosynthetic plants and also suggest that photosynthesis has been lost more recently in the lineage including Pholisma.

References: Barkman, T.J., J.R. McNeal, S.H. Lim, G. Coat, H.B. Croom, N. Young, and C.W. dePamphilis. 2007. Mitochondrial DNA suggests 11 origins of parasitism in angiosperms and reveals genomic chimerism in parasitic plants.  BMC Evolutionary Biology, 7:248.
McNeal, J.R., J.V. Kuehl, J.L. Boore and C.W. dePamphilis. 2007. Complete plastid genome sequences suggest strong selection for retention of photosynthetic genes in the parasitic plant genus Cuscuta.  BMC Plant Biology, 7:57.
McNeal, J.R., K. Arumugunathan, J.V. Kuehl, J.L. Boore and C.W. dePamphilis. 2007. Systematics and plastid genome evolution of the cryptically photosynthetic parasitic plant genus Cuscuta (Convolvulaceae). BMC Biology, 5:55.
Young, N.D. and C.W. dePamphilis. 2005. Rate variation in parasitic plants: correlated and uncorrelated patterns among plastid genes of different function. BMC Evolutionary Biology, 5:16.


Speaker: Dr. Hiroshi Akashi - Department of Biology

Title: Biosynthetic constraints and molecular evolution: Lineage-specific codon usage and protein evolution in the Drosophila melanogaster subgroup


Abstract: Selection pressures related to biosynthetic, as opposed to functional, constraints may act globally in protein as well as “silent” DNA evolution.  In yeast and Drosophila, both amino acid usage and rates of protein evolution show striking associations with gene expression levels.  Genome-scale analyses of four closely related Drosophila lineages show that mutation patterns and selection intensity for codon bias vary frequently on the time-scale of molecular evolution.  Strong departures from steady-state amino acid composition in lineages showing changes in synonymous codon usage suggest that similar forces (such as selection for translational accuracy and efficiency) may act on codon usage and protein evolution.


References: Akashi,  H., 2001  Gene expression and molecular evolution. Current Opinions in Genetics and Development 11: 660-666.


Akashi, H., W.Y. Ko, S. Piao, A. John, P. Goel, C. F. Lin, and A. Vitins, 2006  Molecular evolution in the Drosophila melanogaster species subgroup: Frequent parameter fluctuations on the time-scale of molecular divergence. Genetics 172: 1711-1726.


Speaker: Dr. Masafumi Nozawa - Department of Biology

Title: Copy number changes of histone genes during the evolution of humans and chimpanzees

Recent studies have shown that genomic drift (i.e., random changes of gene copy number) is an important mechanism in the evolution of sensory receptor gene families. However, the importance of genomic drift remains unclear for other multigene families. In this study, we have therefore examined the magnitude of genomic drift in histone gene family, which is thought to be one of the most conserved gene families, using human and chimpanzee data. The results showed that both humans and chimpanzees showed ~100 functional histone genes in their genomes. Interestingly, we also found a considerable number of histone pseudogenes (~100) in both genomes.  Although the extent of copy number variation among human individuals in histone genes was much smaller than that in sensory receptor genes, ~20% of histone genes were still polymorphic with respect to copy number among 270 individuals. In addition, there was no significant difference in the proportion of copy number polymorphic genes between functional and nonfunctional histone genes.  When the evolutionary changes of the number of histone genes were estimated after the divergence of humans and chimpanzees, we found many gains and losses of histone genes, although the total numbers of histone genes have been stable during the evolution of humans and chimpanzees. From these results, we conclude that a part of copy number changes have randomly occurred even in the highly constrained histone gene family.

References: Redon R, et al. (2006) Global variation in copy number in the human genome. Nature 444: 444-454.


Nei M. (2007) The new mutation theory of phenotypic evolution. Proc Natl Acad Sci USA 104: 12235-12242.


Niimura Y and Nei M. (2007). Extensive gains and losses of olfactory receptor genes in mammalian evolution. PLoS ONE 2: e708.


Nozawa M, Kawahara Y, and Nei M. (2007) Genomic drift and copy number variation of sensory receptor genes in humans. Proc Natl Acad Sci USA 104: 20421-20426.


Speaker: Dr. Webb Miller - CANCELLED





Speaker: Dr. Webb Miller - Department of Biology and Yu Zhang - Department of BMB

Title: Primate Gene Clusters


Abstract: We will discuss a collaborative project to sequence and analyze 14 tandem gene clusters in up to 7 primates. The data will be added to that from human, chimpanzee, gorilla (if it is ready), orangutan, rhesus and marmoset. Computational methods to reconstruct the evolutionary history of these clusters will be described, including methods to identify gene-conversion events.

References: No references to post


Speaker: Dr. Benjamin Dickins

Title: Evolved and evolving overlapping reading frames in viruses


Abstract: Viral genomes often encode multiple proteins in overlapping reading frames. Since regions containing overlaps can encode more protein functions and can share regulatory features, overlaps may have evolved in response to selection for genomic and/or regulatory compression (though more frequent emergence in compact, gene-dense genomes cannot be excluded). With a rapid life-cycle and fecund reproductive strategy, viruses offer an excellent system within which to study the biology of overlaps and the dynamics of selection more generally. For example, one study used variation in codon bias between overlapping and non-overlapping gene segments in the Microviridae to evaluate the evolutionary order of overlap emergence [1].

     To explore the effects of selection more directly, I will describe planned experiments, on the Microvirid PhiX174, in which selection is relieved on one member of an overlapping gene pair and the impact of this on substitutions occurring during continuous selection on naive bacterial hosts explored. To evaluate compression hypotheses for the emergence of overlaps, I will also present a preliminary analysis of the properties of overlaps in this and other virus families.


References: [1] Pavesi, A. (2006) Origin and evolution of overlapping genes in the family Microviridae. Journal of General Virology. 87: 1013.