Ancestral maximum likelihood of evolutionary trees is hard

Maximum likelihood (ML) (Neyman, 1971) is an increasingly popular optimality criterion for selecting evolutionary trees. Finding optimal ML trees appears to be a very hard computational task--in particular, algorithms and heuristics for ML take longer to run than algorithms and heuristics for maximum parsimony (MP). However, while MP has been known to be NP-complete for over 20 years, no such hardness result has been obtained so far for ML. In this work we make a first step in this direction by proving that ancestral maximum likelihood (AML) is NP-complete. The input to this problem is a set of aligned sequences of equal length and the goal is to find a tree and an assignment of ancestral sequences for all of that tree's internal vertices such that the likelihood of generating both the ancestral and contemporary sequences is maximized. Our NP-hardness proof follows that for MP given in (Day, Johnson and Sankoff, 1986) in that we use the same reduction from Vertex Cover; however, the proof of correctness for this reduction relative to AML is different and substantially more involved.     

Escape of a plant virus from amplicon-mediated RNA silencing is associated with biotic or abiotic stress

Strong RNA silencing was induced in plants transformed with an amplicon consisting of full-length cDNA of potato leafroll virus (PLRV) expressing green fluorescent protein (GFP), as shown by low levels of PLRV-GFP accumulation, lack of symptoms and accumulation of amplicon-specific short interfering RNAs (siRNAs). Inoculation of these plants with various viruses known to encode silencing suppressor proteins induced a striking synergistic effect leading to the enhanced accumulation of PLRV-GFP, suggesting that it had escaped from silencing. However, PLRV-GFP escape also occurred following inoculation with viruses that do not encode known silencing suppressors and treatment of silenced plants with biotic or abiotic stress agents. We propose that viruses can evade host RNA-silencing defences by a previously unrecognized mechanism that may be associated with a host response to some types of abiotic stress such as heat shock.     

How cells coordinate growth and division

Size is a fundamental attribute impacting cellular design, fitness, and function. Size homeostasis requires a doubling of cell mass with each division. In yeast, division is delayed until a critical size has been achieved. In metazoans, cell cycles can be actively coupled to growth, but in certain cell types extracellular signals may independently induce growth and division. Despite a long history of study, the fascinating mechanisms that control cell size have resisted molecular genetic insight. Recently, genetic screens in Drosophila and functional genomics approaches in yeast have macheted into the thicket of cell size control.     

Haplotype mapping of the bronchiolitis susceptibility locus near<Emphasis Type="Italic"> IL8</Emphasis>

Susceptibility to viral bronchiolitis, the commonest cause of infant admissions to hospital in the industrialised world, is associated with polymorphism at the IL8 locus. Here we map the genomic boundaries of the disease association by case-control analysis and TDT in 580 affected UK infants. Markers for association mapping were chosen after determining patterns of linkage disequilibium across the surrounding region of chromosome 4q, a 550-kb segment containing nine genes, extending from AFP to PPBP. The region has three major clusters of high linkage disequilibrium and is notable for its low haplotypic diversity. We exclude adjacent chemokine genes as the cause of the association, and identify a disease-associated haplotype that spans a 250-kb region from AFM to IL8. In between these two genes there is only one structural feature of interest, a novel gene RASSF6, which is predicted to encode a Ras effector protein.     

From snails to sciatic nerve: Retrograde injury signaling from axon to soma in lesioned neurons

The cell body of a lesioned neuron must receive accurate and timely information on the site and extent of axonal damage, in order to mount an appropriate response. Specific mechanisms must therefore exist to transmit such information along the length of the axon from the lesion site to the cell body. Three distinct types of signals have been postulated to underlie this process, starting with injury-induced discharge of axon potentials, and continuing with two distinct types of retrogradely transported macromolecular signals. The latter include, on the one hand, an interruption of the normal supply of retrogradely transported trophic factors from the target; and on the other hand activated proteins emanating from the injury site. These activated proteins are termed "positive injury signals", and are thought to be endogenous axoplasmic proteins that undergo post-translational modifications at the lesion site upon axotomy, which then target them to the retrograde transport system for trafficking to the cell body. Here, we summarize the work to date supporting the positive retrograde injury signal hypothesis, and provide some new and emerging proteomic data on the system. We propose that the retrograde positive injury signals form part of a complex that is assembled by a combination of different processes, including post-translational modifications such as phosphorylation, regulated and transient proteolysis, and local axonal protein synthesis.     

Ethnicity and human genetic linkage maps

Human genetic linkage maps are based on rates of recombination across the genome. These rates in humans vary by the sex of the parent from whom alleles are inherited, by chromosomal position, and by genomic features, such as GC content and repeat density. We have examined--for the first time, to our knowledge--racial/ethnic differences in genetic maps of humans. We constructed genetic maps based on 353 microsatellite markers in four racial/ethnic groups: whites, African Americans, Mexican Americans, and East Asians (Chinese and Japanese). These maps were generated using 9,291 subjects from 2,900 nuclear families who participated in the National Heart, Lung, and Blood Institute-funded Family Blood Pressure Program, the largest sample used for map construction to date. Although the maps for the different groups are generally similar, we did find regional and genomewide differences across ethnic groups, including a longer genomewide map for African Americans than for other populations. Some of this variation was explained by genotyping artifacts--namely, null alleles (i.e., alleles with null phenotypes) at a number of loci--and by ethnic differences in null-allele frequencies. In particular, null alleles appear to be the likely explanation for the excess map length in African Americans. We also found that nonrandom missing data biases map results. However, we found regions on chromosome 8p and telomeric segments with significant ethnic differences and a suggestive interval on chromosome 12q that were not due to genotype artifacts. The difference on chromosome 8p is likely due to a polymorphic inversion in the region. The results of our investigation have implications for inferences of possible genetic influences on human recombination as well as for future linkage studies, especially those involving populations of nonwhite ethnicity.