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PubMed2001

Cis-acting elements regulate alternative splicing of exons 6A, 6B and 8 of the alpha1(XI) collagen gene and contribute to the regional diversification of collagen XI matrices.

Consecutive exons 6A, 6B, 7 and 8 that encode the variable region of the amino-terminal domain (NTD) of the col11a1 gene product undergo a complex pattern of alternative splicing that is both tissue-dependent and developmentally regulated. Expression of col11a1 is predominantly associated with cartilage where it plays a critical role in skeletal development. At least five splice-forms (6B-7-8, 6A-7-8, 7-8, 6B-7 and 7) are found in cartilage. Splice-forms containing exon 6B or 8 have distinct distributions in the long bone during development, while in non-cartilage tissues, splice-form 6A-7-8 is typically expressed. In order to study this complex and tissue-specific alternative splicing, a mini-gene that contains mouse genomic sequence from exon 5 to 11, flanking the variable region of alpha1(XI)-NTD, was constructed. The minigene was transfected into chondrocytic (RCS) and non-chondrocytic (A204) cell lines that endogenously express alpha1(XI), as well as 293 cells which do not express alpha1(XI). Alternative splicing in RCS and A204 cells reflected the appropriate cartilage and non-cartilage patterns while 293 cells produced only 6A-7-8. This suggests that 6A-7-8 is the default splicing pathway and that cell or tissue-specific trans-acting factors are required to obtain pattern of the alternative splicing of alpha1(XI) pre-mRNA observed in chondrocytes. Deletional analysis was used to identify cis-acting regions important for regulating splicing. The presence of the intact exon 7 was required to generate the full complex chondrocytic pattern of splicing. Furthermore, deletional mapping of exon 6B identified sequences required for expression of exon 6B in RCS cells and these may correspond to purine-rich (ESE) and AC-rich (ACE) exonic splicing enhancers.

Alternative Splicing↗
PubMed1997

Cellular diversification in the vertebrate retina.

The discovery of heterogeneous populations of retinal precursors with sequentially modified fates may help solve the conundrum of conserved histogenesis in the absence of determination either by birthdate or lineage. Combined with a wealth of new data on the exogenous and endogenous factors that influence cellular fate in the retina, models of how complexity is generated are beginning to emerge.

Animals↗
PubMed1999

Control of muscle fibre and motoneuron diversification.

Recent studies have elucidated both the mechanism of early formation of diverse muscle fibre types and the matching of diverse populations of motoneurons to their appropriate muscle targets. Highlights include the demonstration that distinct signals are necessary for the formation of several distinct myoblast populations in the vertebrate somite, the identification of motoneuron subtypes, studies of how motoneurons target appropriate muscles, and rapid progress on the Drosophila neuromuscular system. We propose a model in which four classes of decision control the patterning of both motoneurons and muscles.

Animals↗
PubMed2001

The generation and diversification of butterfly eyespot color patterns.

BACKGROUND: A fundamental challenge of evolutionary and developmental biology is understanding how new characters arise and change. The recently derived eyespots on butterfly wings vary extensively in number and pattern between species and play important roles in predator avoidance. Eyespots form through the activity of inductive organizers (foci) at the center of developing eyespot fields. Foci are the proposed source of a morphogen, the levels of which determine the color of surrounding wing scale cells. However, it is unknown how reception of the focal signal translates into rings of different-colored scales, nor how different color schemes arise in different species. RESULTS: We have identified several transcription factors, including butterfly homologs of the Drosophila Engrailed/Invected and Spalt proteins, that are deployed in concentric territories corresponding to the future rings of pigmented scales that compose the adult eyespot. We have isolated a new Bicyclus anynana wing pattern mutant, Goldeneye, in which the scales of one inner color ring become the color of a different ring. These changes correlate with shifts in transcription factor expression, suggesting that Goldeneye affects an early regulatory step in eyespot color patterning. In different butterfly species, the same transcription factors are expressed in eyespot fields, but in different relative spatial domains that correlate with divergent eyespot color schemes. CONCLUSIONS: Our results suggest that signaling from the focus induces nested rings of regulatory gene expression that subsequently control the final color pattern. Furthermore, the remarkably plastic regulatory interactions downstream of focal signaling have facilitated the evolution of eyespot diversity.

Animals↗
PubMed2001

Diversification of Escherichia coli genomes: are bacteriophages the major contributors?

Determination of the genome sequence of enterohemorrhagic Escherichia coli O157 Sakai and genomic comparison with the laboratory strain K-12 has revealed that the two strains share a highly conserved 4.1-Mb sequence and that each also contains a large amount of strain-specific sequence. The analysis also revealed the presence of a surprisingly large number of prophages in O157, most of which are lambda-like phages that resemble each other. Based on these results, we discuss how the E. coli strains have diverged from a common ancestral strain, and how bacteriophages contributed to this process. We also describe possible mechanisms by which O157 acquired many closely related phages, and raise the possibility that such bacteria might function as 'phage factories', releasing a variety of chimeric or mosaic phages into the environment.

Bacteriophage lambda↗
PubMed2002

The fundamental contribution of phages to GAS evolution, genome diversification and strain emergence.

The human bacterial pathogen group A Streptococcus (GAS) causes many different diseases including pharyngitis, tonsillitis, impetigo, scarlet fever, streptococcal toxic shock syndrome, necrotizing fasciitis and myositis, and the post-infection sequelae glomerulonephritis and rheumatic fever. The frequency and severity of GAS infections increased in the 1980s and 1990s, but the cause of this increase is unknown. Recently, genome sequencing of serotype M1, M3 and M18 strains revealed many new proven or putative virulence factors that are encoded by phages or phage-like elements. Importantly, these genetic elements account for an unexpectedly large proportion of the difference in gene content between the three strains. These new genome-sequencing studies have provided evidence that temporally and geographically distinct epidemics, and the complex array of GAS clinical presentations, might be related in part to the acquisition or evolution of phage-encoded virulence factors. We anticipate that new phage-encoded virulence factors will be identified by sequencing the genomes of additional GAS strains, including organisms non-randomly associated with particular clinical syndromes.

Amino Acid Sequence↗
PubMed2002

Novel piperidinyloxy oxazolidinone antibacterial agents. Diversification of the N-Substituent.

Oxazolidinone antibacterial agents, where the morpholino group of linezolid was replaced with an N-substituted piperidinyloxy moiety, were synthesized and shown to be active against a variety of resistant and susceptible Gram-positive organisms. The functionality attached to the piperidine nitrogen was varied extensively to determine the SAR for this series. One of the most potent compounds, 11, showed in vivo efficacy upon subcutaneous administration in a Staphylococcus aureus Smith murine systemic infection.

Animals↗
PubMed2002

Influence of antibody diversification on the mechanism of haplotype exclusion of immunoglobulin gene expression.

Allelic, or haplotype, exclusion of immunoglobulin gene expression ensures that the products of a single allele or light chain isotype are expressed on the B cell surface. Evidence has accumulated in rodent and primate models to indicate that the products of successful rearrangement regulate this process. In contrast, haplotype exclusion of chicken immunoglobulin gene expression is regulated at the level of variable region gene rearrangement. We discuss here alternative models for ensuring haplotype exclusion that may operate in the chicken and extend the discussion to address the issue as to how two apparently distinct mechanisms may have evolved to yield the same outcome.

Alleles↗
PubMed2003

Patterns of diversification in two African forest shrews: Sylvisorex johnstoni and Sylvisorex ollula (Soricidae, Insectivora) in relation to paleo-environmental changes.

We analysed the phylogeographic patterns of two congeneric and syntopic species of forest shrews and compared them with biogeographical scenarios proposed for the Central African tropical forest. Our results, based on 82 partial 16s rRNA mitochondrial sequences, suggest that both species must have originated in the Plio-Pleistocene and that their haplotype distributions could reflect the effect of forest fragmentation and expansion associated with paleoclimatic fluctuations during the Pleistocene. However, it seems that the two species responded very differently to environmental changes. While Sylvisorex johnstoni populations exhibit ancient haplotype segregation that may even represent currently unrecognised allopatric species, Sylvisorex ollula haplotypes are much less differentiated and suggest that this taxon has undergone a recent range expansion. The observed differences between these taxa may be explained by their presumably different ecological requirements and colonisation abilities, which in turn may be the result of a significant difference in body size between the two species. In conclusion, our results suggest that it is necessary to incorporate several ecologically well-documented species in studies that attempt to infer evolutionary processes from phylogeographic patterns

Africa, Central↗
PubMed2002

Conservation and diversification of gene function in plant development.

The Arabidopsis genome sequence has given us an inventory of the genes needed to specify a flowering plant. Plants are highly diverse in appearance and the mechanisms whereby this diversity has arisen need explanation. A fundamental question is to what extent diversity arises from remodelling of gene function or relocation of gene pathways, rather than from the gain or loss of genes. Similar types of genetic rewiring may be responsible for both intra- and inter-specific differences in developmental processes. Recent advances in the understanding of shoot, flower and leaf development provide insights to this question.

Arabidopsis↗
PubMed2001

Myoblast diversification and ectodermal signaling in Drosophila.

The flight muscles of Drosophila derive from myoblasts found on the third instar disc. We demonstrate that these myoblasts already show distinctive properties and examine how this diversity is generated. In the late larva, Vestigial and low levels of Cut are expressed in myoblasts that will contribute to the indirect flight muscles. Other myoblasts, which express high levels of Cut but no Vestigial, are required for the formation of the direct flight muscles. Vestigial and Cut expression are stabilized by a mutually repressive feedback loop. Vestigial expression begins in the embryo in a subset of adult myoblasts, and Wingless signaling is required later to maintain this expression. Thus, myoblasts are divided into identifiable populations, consistent with their allocation to different muscles, and ectodermal signals act to maintain these differences.

Animals↗
PubMed2001

The development of postganglionic sympathetic neurons: coordinating neuronal differentiation and diversification.

The fine-tuned operation of the nervous system is accomplished by a diverse set of neurons which differ in their morphology, biochemistry and, consequently, their functional properties. The accurate interconnection between different neuron populations and their target tissues is the prerequisite for physiologically appropriate information processing. This is exemplified by the regulatory action of the autonomic nervous system in vertebrates to sustain homeostasis under changing physiological demands. For this purpose, the coordination of divergent regulatory responses is required in a multitude of tissues spread over the entire body. To meet this task, diverse neuronal populations interact at different levels. In the sympathetic system. chemical relations between preganglionic and postganglionic neurons appear to differ along the rostrocaudal axis. In addition, postganglionic neurons innervating different target tissues at a segmental level have distinct properties. Differences in their preganglionic innervation and their integrative membrane properties result in diverse activation patterns upon reflex stimulation. Moreover, postganglionic neurons differ in the transmitter molecules they employ to convey information to the target tissues. The segregation of noradrenaline and acetylcholine to different populations of postganglionic sympathetic neurons is well established. A combination of cellular and molecular approaches has begun to uncover how such a complex system may be generated during development. Growth and transcription factors involved in noradrenergic and cholinergic differentiation are characterised. Interestingly, they can also promote the expression of proteins involved in transmitter secretion. As the proteins participating in the vesicle cycle are expressed in many neuron populations, whereas the enzymes of transmitter biosynthesis are restricted to subpopulations of neurons, the findings suggest that early in neuronal development subpopulation-specific and more widely expressed neuronal properties can be commonly induced. Still, many details concerning the signals involved in the induction of the neurotransmitter synthesis and release machinery remain to be worked out. Likewise, the regulatory processes resulting in differences of electrophysiological membrane properties and the specific recognition between pre- and postganglionic neurons have to be determined. Ultimately, this will lead to an understanding at the molecular level of the development of a nervous system with diverse neuronal populations that are specifically interconnected to distinct input neurons and target tissues as required for the performance of a complex regulatory function.

Animals↗
PubMed2003

Origin, world-wide dispersion, bio-geographical diversification, radiation and recombination: an evolutionary history of Yam mild mosaic virus (YMMV).

We developed an evolutionary epidemiological approach to understand the regional and world-wide dispersion of Yam mild mosaic virus (YMMV) by retracing its evolutionary history. Analyses of the distribution and the prevalence of YMMV in the Caribbean islands of Guadeloupe and Martinique, and in French Guyana revealed that YMMV has a wide repartition and different prevalence on Dioscorea alata L. (Asian and Oceanic origin), on D. cayenensis Lam.-D. rotundata Poir. (African origin) and on D. trifida L. (Amazon and the Caribbean origin) in this region. Considering the data on the current dispersion of the virus and the evolution and the history of the yams, the phylogenetic analysis of the 3' terminal part of the YMMV genome gave a consistent support of the Asian-Pacific origin of YMMV from D. alata species. The YMMV phylogenetic tree is star-like, suggesting an early split of the genetic lineages. An important part of the clades is constituted by a single lineage arisen by recombination. The largest emerging monophyletic group illustrates well YMMV geographical dispersion. This evolutionary pattern contrasts with the one revealed by the African distinct lineages and by the second significant monophyletic group, for which a host adaptation to D. trifida is suggested. The analysis of the pattern of nucleotide substitutions in the CP gene revealed that purifying selection dominates the evolution of the CP of potyviruses and strongly operates on the YMMV. Switching events, radiation, host and geographical adaptation and recombination events are proposed as major traits of YMMV evolutionary history.

3' Flanking Region↗