Genes and Behavior

Kandel Chapter 3

• The physical essence of all living organisms is determined by its genes.

• Genes are sequences of the following 4 chemical BASES

• Adenine• Thymine• Cytosine• Guanine

Hydrogen bonds between C and G, and between T and A determine the stability of the “double elix” forming DNA and other similar nucleic acids

Human cromosomes

Crush course in gene expression:Gene expression = using genes for producing proteins

There are only 4 nucleotide bases (T, C, A, G) and pairing is forced: (T-A and C-G)

A gene is a sequence of bases encoding for a protein .

Cromosomes (DNA, in the nucleus) are series of genes linked together (exons, ~5% of the total length), with long non-coding regions inpterposed in between (introns, ~95% of the total length)

• Cromosomes are series of genes linked together (exons, ~5% of the total length), with long non-coding regions inpterposed in between (introns, ~95% of the total length)

• Three bases (i.e. ATG, or ATT, …encode for the synthesis of ONE aminoacid).

• There are start and stop sequence to signal the beginning or the end of a gene

Proteins (and peptides) are sequences of 20 aminoacids

Transcription of a gene means that DNA (in the nucleus) is temporarily denatured (opened) to create multiple copies of RNA, substantially similar to DNA, but in short pieces encoding for just a gene

RNA is exported from the nucleus to the cytosol where it binds with RIBOSOMES

Three bases (i.e. ATG, or ATT, …encode for the synthesis of ONE aminoacid).

There are start and stop sequence to signal the beginning or the end of a gene

Translation means to use RNA sequences to synthesize a protein

END OF THE CRASH COURSE ON GENE EXPRESSION

Genetics Overview

• 30,000 - 40,000 genes• Two copies of each (except X&Y)

– homozygous– heterozygous

• Dominant vs. Recessive– loss of function– gain of function

“Nature or nurture” problem

To what extent our

genetic backgroundvs.the

external environmentdetermine our behavior

?????

Example: phenylketonuria• 1 in 15,000 children• Recessive mutation • Phenylalanine hydroxylase makes tyrosine• Treatment: reduce phenylalanine in diet

Identical Twin Studies- Raised Apart- Raised Together

Psychological features dependent on genetic or on environmental factors in three different studies

Knock-in or knock-out transgenic animals are valid tools for neuroscience research

Single Genes Contribute to Behavior

• Circadian Rhythm - Period and timeless• Social feeding behavior

– gene resembles the Neuropeptide Y receptor

• Larvae - forager– Worms - solitary vs. social

– Single amino acid substitution in a Neuropeptide Y receptor

In Drosophila two genes linked to circadian oscillations have been thoroughly studied: PER(iod) and TIM(less) genes

They act in tandem as inhibitors of transcription.

One of them is light-sensitive: light impairs its function and the complex stops working as transcription inhibitor

Circadian Rhythm and Genes

• Regulatory oscillations– period and timeless are transcribed in the morning– protein levels build but remain inactive because

timeless is degraded by light exposure– at night timeless/period complexes form and enter

nucleus to inhibit their own transcription– By morning protein levels have fallen and they are

again transcribed

Circadian Mutants

• Long-day period does not bind timeless as well– thus levels must be higher before complex functions

• Mammalian genes including clock are similar

In mice a circadian rhythm gene has been identified:

CLOCK

Yellow indicates light.The black dots represent motor activity (mice are nocturnal animals)

Circadian rythms are compromised in the -/- homozygotic animal

Other mutations affecting behavior

• Leptin – Feeding• Serotonin – Impulsive behavior• Dopamine – Locomotion and motivation• Opsin – Color vision• Huntingtin – Huntington’s Disease

Huntington disease:

As in many other genetic diseases, the mistaken repeat of a triplet (CAG) produces an anomalous protein, of yet unknown function, that is associated with HD symptoms.

The longer the repeat, the younger the age of onset of the disease.

There are two opposite ways in which genes are involved in a disease:

3) A defect in a single gene impairs the function of a protein causing the disease (monogenetic origin, like Huntington disease)

5) The concomitance of more than one defective genes causes the appearance of the symptoms (polygenetic origin, like hypertension and diabetes)

• Schizophrenia has a clearly polygenetic component, involving possibly 3-10 genes.

• The co-existance of specific allelic polymorphisms, that per-se are not pathologic might be at the origin of psychotic symptoms characteristic of schizophrenia