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Transcript
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