Homework 2 is due 1018 Bonus 1 is

• Homework #2 is due 10/18 • Bonus #1 is due 10/25 • Weekly quiz online each Thursday, due each Tuesday Fig 8. 19

Gene Expression is controlled at all of these steps: • DNA packaging • Transcription • RNA processing and transport • RNA degradation • Translation • Post-translational Fig 16. 1

C. elegans is commonly used to study development

C. elegans development

C. elegans mutants with cells that do not develop properly. Fig 12. 25 and

C. elegans mutants with cells that do not develop properly. The product of these genes was found to be RNA?

Micro. RNAs (mi. RNA) are ~22 nt RNAs that play important regulatory roles Cell vol. 116, 281 -297 2004

mi. RNA expressed How do micro. RNAs control gene expression? mi. RNA processed to ~22 nt RNA Mature mi. RNA

A processed m. RNA ready for translation: micro. RNAs inhibit translation by binding to the 3’ end of m. RNA micro. RNA bind to 3’-UTR 5’-UTR 3’-UTR

mi. RNA expressed the 3’ end with attached micro. RNA interacts with the 5’ end, blocking translation mi. RNA processed to ~22 nt RNA Mature mi. RNA

mi. RNAs can lead to methylation of DNA that leads to inhibition of transcription

micro. RNAs primarily target gene products that function during development Tbl 1

tissue specific expression of mouse micro. RNA PNAS vol. 101 #1 pg 360 -365, 2004

Silencing RNAs (si. RNA) are artificially induced ds. RNA Fig 8. 22

si. RNA with exact matches to the target m. RNA causes degradation of the m. RNA Fig 8. 21

micro. RNA Translation inhibited si. RNA m. RNA degraded

Gene Expression is controlled at all of these steps: • DNA packaging • Transcription • RNA processing and transport • RNA degradation • Translation • Post-translational Fig 16. 1

Phosphorylation and dephosphorylation of proteins can change activity Fig 9. 21

Ubiquitinization targets proteins for degradation Fig 9. 23

All protein interactions in an organism compose the interactome

Some proteins function in the cytoplasm; others need to be transported to various organelles.

How can proteins be delivered to their appropriate destinations?

Protein Destinations: secretion or membrane

• Signal sequences target proteins for secretion Fig 9. 24

Translation of secreted proteins

Translation of membrane bound proteins

Translation of secreted or membrane bound proteins This step determines secretion or membrane bound.

Protein Destinations: nucleus Signal anywhere in protein, Translation in cytoplasm, Signal not removed

Protein Destinations: mitochondria or chloroplast Signal translated first, Translation in cytoplasm, Signal removed

Protein Destinations: signals in protein determine destination

Development: differentiating cells to become an organism

Cells function differently because they express different genes.

The proper control of gene expression is critical for proper development.

So development in animals is one way.

Inverse relationship between smoking and weight: more smoking : less weight

Effect of smoking on fetal development and how that can affect adults

Adults exposed to smoke as fetuses have higher risk of obesity and heart disease

What is the connection?

Obesity, Diabetes, Heart Disease, High Blood Pressure, Some Cancers all may have some origins during fetal development.

Adults metabolism may react to poor nutrition as fetuses… Adaptation of Thriftiness or Catch Up Growth.

Adults metabolism may react to poor nutrition as fetuses…Adaptation of Thriftiness or Catch Up Growth. Study of babies born during Dutch famine of 1944 -45…

Adults metabolism may react to poor nutrition as fetuses…Adaptation of Thriftiness or Catch Up Growth. Study of babies born during Dutch famine of 1944 -45… 20 years later found that these babies had higher rates of obesity.

Adults metabolism may react to poor nutrition as fetuses…Adaptation of Thriftiness or Catch Up Growth. Study of babies born during Dutch famine of 1944 -45… 20 years later found that these babies had higher rates of obesity. Precise mechanism is not known

What about smoking? 17, 000 births studied and checked at age 16 and 33. Fetuses exposed to smoking had increased rate of obesity.

What about smoking? 17, 000 births studied and checked at age 16 and 33. Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity.

What about smoking? 17, 000 births studied and checked at age 16 and 33. Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity. For Mom’s who abstained during pregnancy, no effect on fetus or as adult.

What about smoking? 17, 000 births studied and checked at age 16 and 33. Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity. Smoking during first trimester had same effect as during whole pregnancy.

What about smoking? For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes.

What about smoking? Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

Why?

Why? Nicotine can inhibit hunger and increase energy expenditure. This can lead to poor fetal nutrition.

Why? Nicotine causes constriction of blood vessels, and may limit blood flow to the fetus.

Mammalian circulation AAL 38. 8

Nicotine causes blood vessels to constrict

Why? CO in blood decreases delivery of O 2 to fetus.

Why? These are all indirect affects… Nicotine can inhibit hunger and increase energy expenditure. Nicotine causes constriction of blood vessels, and may limit blood flow to the fetus. CO in blood decreases delivery of O 2 to fetus.

Why? Nicotine and other toxins in smoke may directly affect hormones that direct fetal development.

Hormones are molecules produced in one cell and signal another.

Why? Nicotine and other toxins in smoke may directly affect hormones that direct fetal development. Including hormones that direct brain development.

So, Smoking during pregnancy may have indirect and/or direct affects on fetal development, and these affects may manifest themselves in adults.

Correlation of weight and relatedness Correlation of weight (BMI) Biological siblings Parents and children living together Identical twins reared together Fraternal twins reared together Identical twins reared apart Adopted children and parents Unrelated children living together % 34 26 80 43 72 4 1