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Development and Genetics PSC 113 Jeff Schank Outline • A Brief History of Genetics • Gene Expression – Genetics and DNA – Gene Regulation – Hormones and Their Receptors – Genes and Gene Families A Brief History of Genetics • How did we get from Mendelian genetics and having no idea about the physical basis of Mendelian factors to modern genetics? • Sutton-Bovari Hypothesis (1903): – Walter Sutton noticed in a grasshopper species that he was studying that – They had 11 chromosome pairs that were morphologically similar Sutton continued… • after meiosis, each gamete had 11 chromosomes • offspring have 22 chromosomes or 11 similar pairs • He hypothesized that Mendel’s factors were located on chromosomes • That is fertilization by the fusion of ovum (11) and sperm (11) restored 22 chromosomes (i.e., 11 pairs) Metaphase II of meiosis Anaphase of meiosis Thomas Hunt Morgan • And his students: Alfred Sturtevant, Calvin Bridges, and Herman Muller, working with fruit flies (Drosophila) • were able to show that genes (though they had not been physically identified with DNA) mapped to regions of chromosomes • by 1916 they knew genes were parts of chromosomes Thomas Hunt Morgan Gene Expression • Genetics and DNA • Watson and Crick (1953) proposed a model for the DNA molecule (based in large part on the work of Rosalind Franklin) as a chain composed of two strands of sugar phosphate molecules linked together by chemical bases (adenine, cytosine, thymine, and guanine; ACTG) in a double helix formation DNA Replication Keep in mind that although DNA is often called a replicating molecule, but it can only do so in specific biochemical contexts. Transcription and Translation Gene Regulation • Genes express proteins, but there are many ways in which this process can be regulated and influenced • Many transcription factors are proteins encoded by other genes, and thus the products of certain regulatory genes can encode and regulate other genes • This implies that at the molecular level, gene expression is a multistep process, which can be influenced and regulated at every step! Gene Regulation… Hormones and Their Receptors • Steroid hormones (e.g., estrogens) pass through the cell’s membrane and join with receptors to affect cytoplasmic processes, and through the cell’s nuclear membrane to affect transcription directly • Peptide hormones (e.g., oxytocin and vasopressin) may affect the cellular processes by binding with G protein (guanine nucleotidebinding proteins) receptors and initiating second messenger activities that affect cytoplasmic process and/or nuclear processes Caenorhabditis elegans (C. elegans) C. elegans • Has 20,470 genes • Most mammals have 20,000 to 24,000 genes • And yet, mammals (especially humans) are much more complex • How can there such differences in complexity with similar numbers of genes? The Genome as a Network Figure. Gene networks showing inter-relationship between differentially expressed genes in LCL from 3 discordant autistic twin sets using Ingenuity Pathways Analysis software. The over-expressed (red) and underexpressed (green) genes were identified as significant using SAM analysis (FDR = 26.4%) of microarray data across 3 twin pairs. The log2 expression ratio cutoff was set at ± 0.58 and was based upon the mean values for each gene. Genes within this network that have a reported role in nervous system development and function are marked with a "#" symbol and include: ASS, ALOX5AP(FLAP), DAPK1, F13A1, IL6ST, NAGLU, PTGS2, and ROBO1. Gray genes are present but do not meet expression cutoff. Hu et al. BMC Genomics 2006 7:118 doi:10.1186/1471-2164-7-118 Genes and Gene Families Gene families are groups of homologous genes that are likely to have highly similar functions or share similar sequences of DNA From: Demuth, J. P. (2006). The Evolution of Mammalian Gene Families Gene Gain and Loss in Mammals Distribution of gene gains and losses among mammalian lineages. Numbers in parentheses report number of genes gained or lost on each branch. From: Demuth, J. P. (2006). The Evolution of Mammalian Gene Families Humans • Humans have one of the highest rates of gene family evolution (see Table above) with 20 new gene families • Nevertheless, even with a high rate of genetic evolution (relatively speaking), humans evolved from a common ancestor to chimpanzees with only a few hundred gains and losses in genes • The most common biological functions of rapidly changing gene families include: – – – – – – immune defense and response transcription, translation brain and neuron development intercellular communication and transport Reproduction metabolism