高级生物化学与分子生物学1.ppt

1931 重组通过交换而发生 Recombination is caused by crossing over 1944 DNA是遗传物质 DNA is genetic material 1945 基因编码蛋白质 A gene codes for a protein 1953 DNA是双螺旋 DNA is a double helix 1958 DNA是半保留复制 DNA replicates semiconservatively 1961 遗传密码子是三联体 Genetic code is triplet 1977 真核生物基因是断裂的 DNA can be sequenced 1977 DNA可以测序 Genomes can be sequenced 测序细菌基因组 Bacterial genenome sequenced 2001 测序人类基因组 Hunman genenome sequenced (1) The Early Years of Genetics What Did Mendel Find? He discovered different laws and rules that explain factors affecting heredity. Quantifying the number of deleterious mutations per diploid human genome is of crucial concern to both evolutionary and medical geneticists. Here we combine genome-wide polymorphism data from PCR-based exon resequencing, comparative genomic data across mammalian species, and protein structure predictions to estimate the number of functionally consequential single-nucleotide polymorphisms (SNPs) carried by each of 15 African American (AA) and 20 European American (EA) individuals. We find that AAs show significantly higher levels of nucleotide heterozygosity than do EAs for all categories of functional SNPs considered, including synonymous, non-synonymous, predicted ‘benign’, predicted ‘possibly damaging’ and predicted ‘probably damaging’ SNPs. This result is wholly consistent with previous work showing higher overall levels of nucleotide variation in African populations than in Europeans. EA individuals, in contrast, have significantly more genotypes homozygous for the derived allele at synonymous and non-synonymous SNPs and for the damaging allele at ‘probably damaging’ SNPs than AAs do. For SNPs segregating only in one population or the other, the proportion of non-synonymous SNPs is significantly higher in the EA sample (55.4%) than in the AA sample (47.0%; P??2.3?×?10-37). We observe a similar proportional excess of SNPs that are inferred to be ‘probably damaging’ (15.9% in EA; 12