2014师兄考研生化

1、liguofuMembrane Biology （膜生物学）李国富 liguofu1 液晶与生物膜2 细胞的生物膜体系3 膜研究方法简介4 膜脂的提取与分析5 脂质体及其应用 膜生物学1.1 液晶液晶的概念与分类液晶的结构液晶的物理性质 1.2 生物膜生物膜是溶致液晶生物膜的成分及其功能细胞/细胞器的形状问题生命的膜脂起源模型liguofu1.2.4 生命起源的膜脂模型 生命科学的两个根本问题 地球生命起源的可能途径 化学起源的有关问题 Lipid-Assembly-First ScenarioliguofuOntogenesis（个体发育）Space-time processGenomePr

2、oteome Life生命科学的两个根本问题（1）liguofuPhylogenesis（系统发育）Inheritance and EvolutionLife Origin生命科学的两个根本问题（2）liguofu地球外起源外星人带来陨石带来 (Astrobiology)神创论化学起源论（地球） How does the life originated on earth?地球生命起源的可能途径liguofu有较为合理的理解和解释。多种解释，争论较多。生命起源的地表和大气条件。构成生命的砖块，如核苷酸、氨基酸等是如何产生的？他们与现在的核苷酸和氨基酸等相同吗？这些小分子砖块是如何开始构建出生命的

3、？化学起源的有关问题（1）Geophysical ChemicalBiological三个阶段liguofuGeophysicalH2O, CO, CO2, N2, H2S and H2liguofu1953Urey-Miller1938 OparinChemicalliguofuliguofuHow many ideas extracted from the primordial soup?Genes-First ScenarioLipid-Assembly-First ScenarioBiopolymer FirstAssembly First化学起源的有关问题（2）liguofuBiop

4、olymer First (Genes-First) ScenarioWho Was First ? Proteins or Nucleic Acids?liguofuBiopolymer First (Genes-First) Scenario (cntd)liguofuBiopolymer First (Genes-First) Scenario (cntd)liguofu Lipid-Assembly-First ScenarioThe physical features of lifeDid life necessarily begin with biopolymers?Can an

5、assembly code information? GARD modelMathematical descriptionConclusion CommentliguofuThe physical features of life Life is a physical system Compositional complexity Mutually catalytic assembly Far from equilibrium Kinetic homeostasisSelf-replicationInformation storage & transferMutation, selection

6、 and evolutionliguofuDid life necessarily begin with biopolymers?No!很多有机聚集体(organic assembly)具备以上性质.Lipid/lipid-like 等两性分子具有高度多样性，是良好的 candidate.Self-assembly by hydrophobic force. Lipozymes: 具有催化功能的脂质聚集体.liguofuCan an assembly code information? 一个含23个氨基酸残疾的蛋白（有20种氨基酸可供选择），其排列式有2023 种（信息：20log223 10

7、0bit）；一个assembly有23种分子可供选择，每种分子的数目为120，那么assembly的多样性总数也是2023，与前者具有同样多的信息量。liguofuComposition genome信息量（bit）log2排列组合数排列组合数：NGN (sequence) (assembly)N：Sequence length or assembly sizeNG: 单体分子的 种类数（repertoire)信息量为100比特的sequence或assembly所需要的大小和分子的种类数sequenceassemblyliguofuGraded Autocatalysis Replicati

8、on Domain modelGARD model (1)Aseembly可以在相对稳定中进化，即遗传与变异并存。它的机制是什么？liguofuGARD model (2)维持assembly遗传性的机制之一是assembly的大小和组成分子种类的多少：设分子的种类数为m，每个分子在assembly中的平均个数为2r，则在子代assembly中每种分子至少有一个拷贝的概率p = (1-e-r)m.若m4，r16，则p 1，但若r2，则p 0.55.liguofuGARD model (2)维持assembly遗传性的机制之二是assembly中的不同成员间的Mutually catalytic

9、 interactions. 对于没有这种内在性质的assembly，外环境中的各种分子随机进入assembly，没有偏好性，导致子代随机地偏离父代的促成，遗传性大大降低。No catalysisliguofuGARD model (3)如果assembly中的不同成员间存在Mutually catalytic interactions，外环境中的各种分子进入assembly就会有选择性，子代的compositional genome与父代非常相似，遗传性增强liguofuGARD model (4)Mutually catalytic interactions有强弱之分liguofuGARD

10、 model (5)Mutually catalytic interactions的强弱差别使各种分子在assembly中地位并不均等，遗传给子代的概率当然不同，这是变异和进化的基础。liguofuGARD model (6)Graded Autocatalysis Replication Domain modelliguofuMathematical description (1)liguofuMathematical description (2)liguofu(4)liguofu The main reaction step, in the simplest amphiphilic GA

11、RD formulation, is the transfer of an amphiphilic molecule Ai between the environment and an assembly (straight arrows). A key aspect in reaching a kinetic homeostasis is the dependence of the reaction rates on the current composition of the assembly. Here, kf and kb are forward and backward basal r

12、ate constants, i are exernal concentrations of the different chemical species. The matrix ij signifies the mutual rate enhancement parameters for the catalysis exerted by species Aj on the joining and leaving reactions of Ai (curved arrow). The matrix elements are drawn from a probability distributi

13、on generated through the Receptor Affinity Distribution model.Mathematical description (4)liguofuSome concrete computer simulation results are available in PNAS paper. If interested, please read it. Compositional genomes: Prebiotic informationtransfer in mutually catalytic noncovalent assemblies. Pr

14、oceedings of the National Academy of Science. 2000, 97: 41124117Mathematical description (5)liguofuConclusion (1) No diversity of assembliesNo selection possibleliguofuHigh diversity of assembliesSelection by mutual catalysisNatural selection and evolutionConclusion (2) liguofuConclusion (3) Natural

15、 selection and evolutionliguofuConclusion (4) liguofuConclusion (5) RNA chemistryMolecular self-replicationLipid vesiclesappearanceProteinsappearanceProtocellSelf-assembly of lipidsCompositionalSelf-replicationEvolution and internal self-organizationCompartment formation and polymerizationliguofuComment (1)Li