?

?

Origin of mitochondria and chloroplasts: Both mitochondria and chloroplasts are believed to be derived from endosymbiotic bacteria. Endosymbiotic bacteria = free-living prokaryotes that invaded ancestral eukaryotic cells and established a mutually beneficial relationship. Many required mitochondria and chloroplast proteins also are coded by nuclear genes. numt = nuclear mtDNA (mtDNA transposed to the nucleus)

Time-line of life on earth Origin of life Multicellular life Cambrian explosion First land plants Oxygen appears First vertebrates 3800MY 2500MY 1000MY 530MY 410MY

Origin of Eukaryotic Diversity

Organelle genomes Genome Size & Organization Plant plastid 150 kb circle Plant mitochondria 150 – 2000 kb multipartite Human mitochondria 17 kb circle saccharomyces mitochondria 75 kb circle Encode only a subset of genes required to elaborate a functional organelle rRNAs, tRNAs, ribosomal proteins, membrane-associated respiratory or photosynthetic components Other components encoded by nuclear genome, translated in the cytosol and imported into the organelle 10% of nuclear genes devoted to mitochondrial function; 15% of nuclear genes devoted to plastid function Associated with proteins and organized into structures called nucleoids (not the same as nucleosomes found in nuclear chromatin)

Eukaryotes Organelle-Genomes Ribosomal RNA sequences suggests that plant plastids share common ancestor with modern Cyanobacteria such as Synechococcus lividus Mt-rRNA share greatest homology with members of alpha-group of proteobacteria which includes intracellular parasites (Agrobacterium, Rhizobium)

Mitochondria make up some 80% of the volume of the cone cell photoreceptors of the eye and 40% of the volume of heart muscle cells.

Mitochondria are essential for oxidative phosphorylation (make ATP)

Mitochondria are essential for oxidative phosphorylation (make ATP) However they play important roles in most other metabolic functions of the cell: * Pyrimidine synthesis * Heme synthesis (red blood precursor cells) * Amonia detoxification (liver) * Cholesterol metabolism * Sex hormone synthesis * Free radical production and detoxification * Apoptosis

In fact out of the 3000 genes required to make a mitochondrion only 100 are concerned with making ATP.

(human: 2-10 mtDNA per mitochondrion)

Chloroplast DNA-Microscopic Image Electron microscopic image of a circular DNA molecule isolated from a soybean chloroplast (a ctDNA) N.M. Chu, K.K. Tewari, 1982. 1 µm

Fig. 15.2, mtDNA replication

Transcription of the mtDNA genome: mRNAs from the mtDNA are synthesized and translated in the mitochondria. Gene products encoded by nuclear genes are transported from the cytoplasm to the mitochondria. Mammalian mtDNA is unusual as it is transcribed as a single large RNA molecule and then cleaved to produce mRNAs, tRNAs, and rRNAs before they are processed. Most mtDNA genes are separated by tRNAs that signal transcription termination.

No coded stop codons

Mitochondrial code Universal code

Wobble G U/C C G A U U A/G Wobble rules: 32 tRNAs required

More Wobble in mitochondria 22 tRNAs required

Fig. 15.3, Physical map of the human mtDNA

?

Mitochondrial DNA mutations in human genetic disease (Wallace Sci. Amer. 277:40)

Examples of maternally inherited human mtDNA defects: Leber’s hereditary optic neuropathy (LHON), OMIM-535000 Midlife adult blindness from optic nerve degeneration. Mutations in ND1, ND2, ND4, ND5, ND6, cyt b, CO I, CO II, and ATPase 6 inhibit electron transport chain. Kearns-Sayre Syndrome, OMIM-530000 Paralysis eye muscles, accumulation of pigment and degeneration of the retina, and heart disease. Deletion of mtDNA tRNAs. Myoclonic epilepsy & ragged-red fiber disease (MERRF), OMIM-545000 Spasms and abnormal tissues, accumulation of lactic acid in the blood, and uncoordinated movement. Nucleotoide substitution in the mtDNA lysine tRNA. Most individuals with mtDNA disorders possess a mix of normal and mutant mtDNA, therefore severity of diseases varies.

Mitochondrial DNA mutations in human genetic disease (Wallace Sci. Amer. 277:40)

Mitochondrial DNA polymorphisms track human migrations (Wallace Sci. Amer. 277:40) All humans descend from a small group of Africans This group originated in central Africa ~200,000 years ago The founding group was small (102-104 people) Descendants of this group replaced all other hominids everywhere in the world

Maternal effect: Some maternal phenotypes are produced by the nuclear genome rather than the mtDNA/cpDNA genomes. Proteins or mRNA (maternal factors) deposited in the oocyte prior to fertilization. Genes for maternal factors occur on nuclear chromosomes; no mtDNA is involved e.g., shell coiling in the snail Limnaea peregra. Determined by a pair of nuclear alleles; D produces dextral (right-handed) coiling, d produces sinistral (left-handed) coiling. Shell coiling always is determined by the maternal genotype, not the alleles that the progeny carry or maternal phenotype. If coiling were controlled by an extranuclear gene, progeny would always have the same phenotype as the mother. Cause-mother snail deposits products in the egg that regulate orientation of the mitotic spindle and direction of cell cleavage.

Fig. 15.14 dextral sinistral *****dextral ***** *****dextral *****

Plant Cell

Higher Plant Chloroplasts

Fig. 15.5 cpDNA of rice

Examples of non-Mendelian inheritance: Variegated-shoot phenotypes in four o’clocks Mixed chloroplasts White/green Mutant chloroplast White non-photosynthetic Normal chloroplast Green photosynthetic Fig. 15.6b

Fig. 15.7 Chloroplasts are inherited via the seed cytoplasm 3 types of eggs (female): Normal Mutant Mixed Assumption: Pollen (male) contributes no information

The search for new antimalarial drugs Malaria is one of the leading causes of morbidity and mortality in the tropics. 300 to 500 million estimated clinical cases and 1.5 million to 2.7 million deaths per year. Nearly all fatal cases are caused by Plasmodium falciparum. The parasite's resistance to conventional antimalarial drugs such as chloroquine is growing at an alarming rate.

DOXP reductoisomerase P. falciparum has a plastidlike organelle, called the apicoplast, acquired by endosymbiosis of an alga. Apicoplast contains enzymes found in plant and bacterial, but not animal metabolic pathways. Potential target for antimalerial drugs: DOXP reductoisomerase Jomaa et al. (1999)

Endosymbiosis