9 Results
for author "Yue-wen Wang"
Figure 1.—(A) Classification of amino acid configurations for two duplicate gene clusters. Type 0 sites are universally conserved through the whole gene family. Type I sites are very conserved in one cluster but highly variable in the other. Type II sites are very conserved in both clusters but with very different biochemical properties. Type U sites are unclassifiable. (B) A diagram shows the stochastic nature of molecular evolution. Each site (represented as a box) has a nonzero probability for any type of amino acid configuration. At site 1 or 2, no altered functional constraint occurs in either cluster, a status defined as S0 = (F0, F0). At site 3, 4, or 5, altered functional constraint occurs in at least one cluster, a status defined as S0 = (F1, F0) or (F0, F1) or (F1, F1) (see methods for details). (C) A flow chart to illustrate Gu's (1999) method.
Figure 2.—The phylogenetic tree of the caspase gene family, inferred by the neighbor-joining method on the basis of the amino acid sequence with Poisson correction. Bootstrap values >50% are presented. Initiator caspases (I-casps) are involved in upstream regulatory events, and effector caspases (E-casps) directly lead to cell disassembly. The accession numbers for protein sequences are (1) casp-3, U13737 (human 3-α), U13738 (human 3-β), U49930 (rat 3-α), U58656 (rat 3-β), Y13086 (mouse), U27463 (hamster), AF083029 (chicken), D89784 (frog); (2) casp-7, U37448 (human), Y13088 (mouse), AF072124 (rat), U47332 (hamster); (3) casp-6, U20536 (human), AF025670 (rat), Y13087 (mouse), AF082329 (chicken); (4) casp-8, AF102146 (human), AF067841 (mouse); (5) casp-10, U60519 (human 10a), U86214 (human 10/b), AF111345 (human 10/d); (6) casp-9, U60521 (human); (7) casp-2, U13021 (human), U77933 (rat), Y13085 (mouse), U64963 (chicken); (8) casp-14, AF097874 (human), AJ007750 (mouse); (9) casp-1, X65019 (human), AF090119 (horse), L28095 (mouse), U14647 (rat), D89783 (frog ICE-A), D89785 (frog ICE-B); (10) casp-4, Z48810 S78281 (human); (11) casp-5, X94993 (human); (12) casp-13, AF078533 (human); (13) casp-11, Y13089 (mouse); (14) casp-12, Y13090 (mouse); (15) invertebrate caspase, P42573 (C. elegans CED-3), Y12261 (Drosophila melanogaster), U81510 (armyworm, Spodoptera frugiperda).
Figure 3.—A schematic of evolution of caspase-mediated pathways. Note that the ancestral function of caspases (as well as the origin of ICE-type caspases) is uncertain. A–C correspond to ancestral nodes in Figure 1. Bcl-2/Apaf, BCR, death receptors (DRs), TNFR1, and CD95 are death signals for specific apoptotic pathways. Caspase-3/-6/-7 are effector caspases (E-casps), which are the real killer proteins in programmed cell death.
Figure 4.—(A) The site-specific profile for predicting critical amino acid residues responsible for the functional divergence between CED-3 and the ICE subfamilies, measured by the posterior probability of being functionally divergence related at each site [P(S1|X)]. The arrows point to four amino acid residues at which functional divergence between two subfamilies has been verified by experimentation. (B) Four predicted sites that have been verified by experimentation.
Figure 5.—Alignment of predicted regions of caspases. Four predicted sites with experimental evidence are highlighted. The sites with asterisks are predicted residues within this region. The boxed region in the C terminus is the critical region for CED-3 substrate specificity: Most CED-3-type caspases form a surface loop, whereas a shallow depression is found in ICE-type caspases.- TABLE 1θ values and dF values from pairwise comparisons in the CED-3 subfamily
Figure 6.—(A) A star-like topology of the CED-3 caspases in terms of type I functional branch length bF. Biological evidence of functional specification for each caspase cluster is shown in the stacked boxes. (B) Functional branch length (bF) and the ratio of nonsynonymous to synonymous rates (dN/dS) for each gene cluster, which were computed by using human-mouse sequences.