Sun,
Apr 13, 2008
Selection constraints on selfish homing endonucleases facilitate their use in gene therapy
Eyal Privman
Homing
endonuclease genes (HEGs)
usually reside in selfish transposable introns and inteins. They code for nucleases that cleave DNA at a
highly specific site within homologs of their hosting
gene that are lacking the intron/intein, thereby
inducing homologous recombination, effectively copying the intron/intein
into the homolog. In this so-called "homing" process HEGs facilitate the horizontal propagation of the intron/intein.
Here we characterize the selection constraints arising from coevolution
of the parasitic HEG with its target sequence in the hosting gene, and use them
to infer the range of sequences that may be recognized and cleaved by the HEG. HEGs have been demonstrated to be a potential tool for gene
targeting in mammalian cells (replacing an endogenous gene sequence). Thus, HEGs can be used to correct mutated genes and serve as a
powerful tool for gene therapy. Our inference of a wide target range can be
harnessed to detect potential HEG targets in the human genome. Thereby, the
potential for finding a HEG in the natural repertoire that will be applicable
in the treatment of a specific disease-related human mutation is increased by
several orders of magnitude.
Mon, Apr 14, 2008
Evolution in varying environments: rapid emergence of modular systems
Nadav Kashtan
Biological networks have an inherent simplicity: They are modular, with a design that can be separated into units that perform almost independently. Little is known about the evolutionary origin of these properties. Current models of biological evolution typically produce highly optimal non-modular networks. Here we suggest a possible explanation for the origin of modularity in biology. We use evolutionary simulations in the computer to evolve networks. The new feature in our study is evolution under an environment (evolutionary goal) that changes in a modular fashion. That is, we repeatedly switch between several goals, each made of a different combination of sub-goals. We find that such 'modularly varying goals' lead to the spontaneous evolution of modular network structure. The resulting networks rapidly evolve to satisfy each of the different goals. Such switching between related goals may represent biological evolution in a changing environment that requires different combinations of a set of basic biological functions. We further find that modularly varying goals dramatically speed up evolution compared to evolution under a fixed goal. This study suggests that modularly varying environments promote modularity and significantly contribute to the speed of natural evolution.
Tues, Apr 15, 2008:
The
evolution of polyembryony in parasitoid wasps
Michal Segoli
Polyembryony is a unique mode of development that involves the production of several genetically identical embryos from a single egg through clonal division. This development style appears to carry a high price tag, because it clones an unproven genotype at the expense of genetic diversity in a brood. Polyembryony nevertheless occurs in several taxa, and is relatively common in parasitoid wasps, suggesting a high adaptive value for polyembryony in the life history of this group. In this talk I will review several hypotheses for the selective forces driving the evolution of polyembryony in parasitoids. The first hypothesis suggests that polyembryony has evolved in situations where parents cannot foresee the future environment for the development of their offspring. Thus, parents pass on the control over brood size to the offspring themselves. The second hypothesis suggests that the production of clonal offspring reduces genetic conflict among them, and improves the offspring's host utilization and defense against competitors. A third possibility is that polyembryonic development allows each parasitoid to produce many offspring, in spite of its small size. This may be especially beneficial if hosts are difficult to locate, and if small body size does not greatly reduce searching efficiency. Finally, polyembryony may allow producing more offspring from each host, when small host size restricts the number of eggs that can be laid in it. This is based on the assumption that parasitoids are limited by the number of suitable hosts rather than by the number of eggs that they can produce. I will present experimental evidence that allows evaluation of these hypotheses, based on a present study of the polyembryonic wasp Copidosoma koehleri, and on previous studies of additional polyembryonic species.
Wed, Apr 16, 2008:
Ofir Cohen
Probabilistic models describing the evolution of macro genomic events such as gene gains
and losses are considerably less developed than models describing site-specific
sequence evolution. We present a novel likelihood-based evolutionary model
which enables inferring gene gains and losses, where gene gain is correlated to
horizontal gene transfer (HGT). In our study, each column of the
"alignment" represents a gene family, in which presence or absence is
designated for all species. The likelihood of these data is calculated by
assuming a Markovian process over the {0,1} alphabet along a given phylogenetic
tree. Our main novelty is the introduction of among-gene-rate-variability,
which better accounts for differences in the rates of gain and loss of
different gene families. Furthermore, we compute the posterior expectation of
the number of transitions for each gene family and at each lineage. This enables
ranking various genes and lineages according to their tendency to undergo gene
gains and losses. We analyzed 4,593 different gene families spanning 282
prokaryotes. Our results revealed both specific genes and entire functional
categories with higher tendency to undergo HGT. In agreement with the
complexity hypothesis, we found
enrichment in genes related to METABOLISM and depletion in INFORMATION STORAGE
AND PROCESSING genes.