线粒体基因组PPT学习教案

1、会计学1Mitochondrial molecular genetics focus on mitochondria: brief overview of their function and structure mtDNA structure and replication:- animals- yeast- plants inheritance of mitochondria - petite mutants of yeast biogenesis of mitochondria by fission第1页/共78页MITOCHONDRIA essential for cell life-

2、 ATP synthesis- many metabolic intermediates essential for cell death - unprogrammed death: necrosis( eg, due to loss of energy status) - programmed cell death(apoptosis - controlled cell destruction)第2页/共78页 Two membranes Inner membrane invaginated Numbers of mitochondria per cell vary but usually

3、100s/cellMatrix contains the TCA cycle (and other) soluble enzymesInner membrane contains metabolite transporters and the electron transport chainMitochondrial structure第3页/共78页The ribosomes can actually be visualized in some mitochondria. In these figures, they are seen in the matrix as small dark

4、bodies. DNA can also be visualized in mitochondria. The DNA is circular and resembles that of a bacterium in its basic structure. Mitochondria also have their own ribosomes and tRNA: 22 tRNAs rRNAs (16S and 12S)第4页/共78页Mitochondria contain DNA molecules with an assortment of genes.Mitochondrial gene

5、tic system consist of DNA and the molecular machinery needed to replicate and express the genes contained in this DNA. This machinery includes the macromolecules needed for transcription and translation. Mitochondria even possess their own ribosomes. Many of these macromolecules are encoded by mitoc

6、hondrial genes, but some are encoded by nuclear genes and are therefore imported from the cytosol.第5页/共78页Mitochondria have their own DNA and RibosomesMitochondria have some of their own DNA, ribosomes, and can make many of their own proteins. The DNA is circular and lies in the matrix in structures

7、 called nucleoids. Each nucleoid may contain 4-5 copies of the mitochondrial DNA (mtDNA).mitochondrialDNA第6页/共78页第7页/共78页第8页/共78页第9页/共78页第10页/共78页第11页/共78页Intramolecular recombination in the mtDNA of the Chinese cabbage, Brassica campestris油菜. Recombination between the repeated elements in the large

8、 circular DNA molecule partitions this molecule into two smaller ones. Alternatively, the repeated elements in the two small molecules may recombine with each other to produce a single large molecule.第12页/共78页第13页/共78页第14页/共78页第15页/共78页第16页/共78页第17页/共78页第18页/共78页第19页/共78页Expression of Mitochondrial

9、genes第20页/共78页Expression of Mitochondrial genes第21页/共78页Expression of Mitochondrial genes第22页/共78页Expression of Mitochondrial genes第23页/共78页Expression of Mitochondrial genes分子内(intramolecular) 剪接(cis splicing) 以及分子间(intermolecular) 剪接(trans splicing) 第24页/共78页第25页/共78页第26页/共78页第27页/共78页第28页/共78页第29页

10、/共78页mt DNA and human disease第30页/共78页第31页/共78页第32页/共78页第33页/共78页Genetic organization of the chloroplast DNA in the liverwort Marchantia polymorpha. Symbols: rpo, RNA polymerase; rps, ribosomal proteins of small subunit; rpl and secX, ribosomal proteins of large subunit; 4.5S, 5S, 16S, 23S, rRNAs of

11、 the indicated size; rbs, ribulose bisphosphate carboxylse; psa, photosystem I; psb, photosystem II; pet, cytochrome b/f complex; atp, ATP synthesis; infA, initiation factor A; frx, iron-sulfur proteins; ndh, putative NADH reductase; mph, chloroplast permease (?); tRNA genes are indicated by abbrevi

12、ations for the amino acids.第34页/共78页第35页/共78页第36页/共78页 Chloroplast biogenesis. A mature chloroplast containing stacks (堆) of thylakoid类囊体 membranes (grana基粒) within its protoplasmic stroma (基质) develops from a proplastid after exposure to light.第37页/共78页第38页/共78页Mitochondrial InheritanceYeast has be

13、en used extensively to study mitochondrial inheritance.There is a Yeast strain, called Petite小型菌聚落 that have structurally abnormal mitochondria that are incapable of oxidative phosphorylation. These mitochondria have lost some or all of their DNA. Genetic crosses between petite and wt (wild-type) st

14、rains showed that inheritance of this trait did not segregate with any of the nuclear chromosomes. 第39页/共78页Mitochondrial inheritance from yeast is biparental双亲的, and both parent cells contribute to the daughter cells when the haploid cells fuse. After meiosis and mitosis, there is random distributi

15、on of mitochondria to daughter cells. If the fusion is with yeast that are petite and yeast that are not, a certain percentage of the daughter cells will be petite. Mitochondrial Inheritance第40页/共78页Mitochondrial Inheritance in Yeast第41页/共78页又称不均等的有丝分裂分离又称不均等的有丝分裂分离第42页/共78页在连续的细胞分裂过程中，异质性细胞中突变型在连续的

16、细胞分裂过程中，异质性细胞中突变型mtDNAmtDNA和野生和野生型型mtDNAmtDNA的比例会发生漂变，向同质性的方向发展。分裂旺盛的比例会发生漂变，向同质性的方向发展。分裂旺盛的细胞（如血细胞）往往有排斥突变的细胞（如血细胞）往往有排斥突变mtDNAmtDNA的趋势，经无数次的趋势，经无数次分裂后，细胞逐渐成为只有野生型分裂后，细胞逐渐成为只有野生型mtDNAmtDNA的同质性细胞。突变的同质性细胞。突变mtDNAmtDNA具有复制优势，在分裂不旺盛的细胞（如肌细胞）中逐具有复制优势，在分裂不旺盛的细胞（如肌细胞）中逐渐积累，形成只有突变型渐积累，形成只有突变型mtDNAmtDNA的同质

17、性细胞。漂变的结果，的同质性细胞。漂变的结果，表型也随之发生改变。表型也随之发生改变。第43页/共78页This led to the suggestion that some genetic element existed in the cytoplasm and was inherited in a different manner from nuclear genes. This is called “non-Mendelian inheritance” or “cytoplasmic inheritance”.Mitochondrial InheritanceIn yeast and

18、animals, this indicated inheritance of mitochondrial genes: in plants it also includes inheritance of chloroplast genes第44页/共78页Mitochondrial replication第45页/共78页Mitochondria replicate much like bacterial cells. When they get too large, they undergo fission. This involves a furrowing of the inner an

19、d then the outer membrane as if someone was pinching the mitochondrion. Then the two daughter mitochondria split. Of course, the mitochondria must first replicate their DNA. An electron micrograph depicting the furrowing process is shown in these figures. Mitochondrial replicationcell division: rand

20、om distribution of mitos between daughter cellsmitochondrialreplication第46页/共78页Sometimes new mitochondria are synthesized in centres that are rich in proteins and polyribosomes needed for their synthesis. The electron micrograph in the following figure shows such a centre. It appears that the clust

21、er of mitochondria are sitting in a matrix of proteins and other materials needed for their production. 第47页/共78页Certain mitochondrial proteins are needed before the mitochondria can divide.They showed the result of the removal of an outer membrane protein from mitochondria called MDM10. This figure

22、 shows the results. The mitochondria are able to take in components and produce membranes and matrix enzymes. However, fission is not allowed and the result is a giant mitochondrion. giant mitochondrion第48页/共78页Human mtDNA small, double stranded circular chromosome 16,569 bp in total no non-coding D

23、NA no introns polycistronic replication which is initiated from the D (displacement)- loop region followed by splicing of transcript to form messages.Organisation of the mitochondrial chromosome第49页/共78页human mtDNAyeast mtDNAYeastmitochondrial chromosome第50页/共78页Human DNA 16,569 bp; no non-coding DN

24、A no introns polycistronic replication followed by splicing to form messages. Yeast mtDNA 68-75 kb, similar in structure to bacterial genome contains introns and non-regions between genes. Same proteins made as in animals genes transcribed separately第51页/共78页Despite having their own genome, most mit

25、ochondrial proteins are encoded in the nucleus, made in the cytosol and imported into the mitochondria.第52页/共78页In all organisms, only a few of the proteins of the mitochondrion are encoded by mtDNA, but the precise number varies between organisms Subunits 1, 2, and 3 of cytochrome oxidase Subunits

26、6, 8, 9 of the Fo ATPase Apocytochrome b subunit of complexIII Seven NADH-CoQ reductase subunits (except in yeast)The nucleus encodes the remaining proteins which are made in the cytosol and imported into the mitochondrion. Synthesis of mitochondrial proteins第53页/共78页Plant mtDNA chromosome size is m

27、uch bigger but varies dramatically between species (200-2000 kb) arranged as different size circles, sometimes with plasmids. The plant mtDNA contains chloroplast sequences, indicating exchange of genetic information between organelles in plants. Much of the plant mtDNA is non-coding, but coding reg

28、ions are larger than animals and fungi. Number of proteins synthesised not known definitely but more than in animals and yeast (probably about 50)第54页/共78页Plant mitochondria have specialised functions in leaves they participate in photorespiration sites of vitamin synthesis (vit C, folic acid, bioti

29、n)第55页/共78页maize mitochondrial genome第56页/共78页In plants, respiration and photosynthesis operate simultaneously in the lightNIGHTDAY第57页/共78页Chloroplasts are the site of photosynthesis and belong to the plastid family of organelles - they develop from proplastids in the lightproplastidamyloplast (in

30、storage organs)第58页/共78页Rice mitochondrial and chloroplast genomesPlant mitochondria contain chloroplast genes - suggesting that genetic transfer occurs between the two organelles第59页/共78页Mitochondrial DNA of animals and fungi uses a different genetic code than the “universal” code第60页/共78页RNA proce

31、ssing in mitochondriaPlant mitochondria “edit” their RNA transcripts. This was first noticed when comparing cDNA sequences with genomic DNA sequences.The most common change is to replace C with U, although in some instances other changes can occur. Matrix enzymes are thought to be responsible for th

32、is, but the reason for the editing is not known.Most of the DNA in plant mitochondria is non-coding, only some of which is transcribed. RNA editing occurs even in non-coding regions such as introns.第61页/共78页第62页/共78页第63页/共78页第64页/共78页Life on earth originated more than 3 billion years ago. The first

33、cellular organisms were prokaryotic; they lacked true nuclei and cytoplasmic organelles and were heterotrophic.Eukaryotic organisms evolved 1 to 1.5 billions years ago. The first known eukaryotes were filamentous green algae, with nuclei and elaborate intracellular organization, including subcellular organelles.In the 1970 Lynn Margulis forcefully argued that both mitochondria and chloroplasts were once free-living o