Nosce te ipsum the human genome University of California,你nosce Ipsum the Human Genome 加州大学.pptVIP

Nosce te ipsum:the human genome 3.3 billion base pairs C-value paradox Amount of DNA = f (organism complexity) human (3.3?109) fly yeast bacteria Amphibia human Tulip = 10x human [sic!] Amoeba dubia = 200x human Broad bean = 4x kidney bean Lily = 100x Arabidopsis ? unicellular organisms are under selective pressure to have small genomes How to measure the “complexity” and composition of a genome Shear the DNA to a size of about 400 bp. Denature the DNA by heating to 100oC. Slowly cool and take samples at different time intervals. Determine the % single-stranded DNA at each time point. The shape of a Cot curve for a given species is a function of two factors: the size or complexity of the genome the amount of repetitive DNA within the genome C0t curve “Why sequence junk?!” ~50% of genome is repetitive DNA ~5% of genome is genes Genome sequencing costs $1 a base. = 3.3 billion dollars to sequence the genome S. Brenner – Fugu (pufferfish) – compact genome! Say again? Repeats: ~45% of genome L1 (LINE) – non-LTR retrotransposon “L1s account directly or indirectly for about one-third of the human genome…” Alu (SINE) – 7SL RNA gene 7SL – component of the SRP Most Alu elements are inactive A few Alu elements can still retropose, are mutagenic, and cause disease: Wallace et al. (Collins) (1991) A de novo Alu insertion results in neurofibromatosis type 1 Nature. 1991 Oct 31;353(6347):864-6. The cost of sexual reproduction Sexual reproduction favors Tn propagation because the fitness of a transposon is twice that of its host Positive correlation between dependence on sex for reproduction and Tn aggressiveness in germline Vertebrates, of course, are obligate sexual outcrossers Simple point Must map genome before sequencing it: individual sequence read 1,000 bp The first map Botstein D, White RL, Skolnick M, Davis RW. Am J Hum Genet 1980 32(3) Construction of a genetic linkage map in man using restriction fragment length polymorphisms.We describe a new basis fo