Clase 1 introducción a la genética etc - Diego Chavez

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Clase	1.	Biología	II
Clase	1.	Historia	de	la	genética.	Objeto	de	estudio	de	la	genética	y	la	
genómica.	Revisión	de	conceptos	básicos:	estructura	del	ADN,	cromatina,	
cromosoma,	definición	y	funciones	del	gen,	¿un	gen:	una	proteína?,	
origen	de	la	variación	genética:	mutación	y	recombinación,	importancia	
de	la	diversidad	genética	para	la	evolución.
http://www.nature.com/principles
Historia	de	la	genética
La herencia. 
Los caracteres hereditarios
Noooooo, no te descargamos de 
Internet, tú naciste... 
Genética y herencia
Gregor	Mendel
Drosophila melanogaster
El	asesoramiento	médico	
puede	prevenir	la	aparición	
de	algunas	enfermedades	
genéticas	en	los	bebés	de	
una	pareja.
Hershey and Chase also ruled out proteins
Griffith: descubrimiento del “principio transformador” 1928
Griffith’s	and	AMM	experiments
http://www.dnaftb.org/17/animation.html
http://www.cubocube.com/dashboard.php?a=1179&b=1224&c=103
AMM’s	
experiment
Wikipedia
35S 32P
The 
Hershey-
Chase 
experiment 
(1952)
Pruebas	adicionales	de	que	el	
material	genético	es	ADN
• El	ADN	viral	por	sí	solo	(sin	las	cápsides)	es	suficiente	para	
transformar	protoplastos	de	bacterias	(sin	pared	celular)		
• Tecnología	de	ADN	recombinante:	al	insertar	ADN	
eucariótico	en	plásmidos	la	bacterias	pueden	producir	
proteínas	
• El	ADN	y	el	ARN	absorben	la	luz	UV	de	260	nm,	la	misma	
que	causa	mutaciones	
• El	ADN	se	encuentra	en	el	núcleo,	mientras	que	las	
proteínas	están	en	todas	las	partes	de	la	célula
By the early 1950s, scientists knew that DNA 
consists of repeating units, or monomers, 
called nucleotides (Figure 6). Each nucleotide 
consists of a nitrogenous base, a 
deoxyribose sugar and a phosphate group. 
There are two types of nitrogenous bases in 
DNA: pyrimidines and purines. The two 
pyrimidine bases in DNA are cytosine (C) 
and thymine(T). The two purine bases 
are adenine (A) and guanine (G). The 
phosphorus in the phosphate group explains 
why the radioactive phosphorus in the 
Hershey-Chase experiment was associated 
with the genetic material of the bacteriophage.
A DNA molecule is a polymer made up of nucleotide monomers. Each nucleotide consists of a nitrogenous base 
that is either a pyrimidine or a purine, along with a deoxyribose sugar and a phosphate group.
Alternative DNA structures
A-DNA, B-DNA Z-DNA 
If	a	molecule	is	composed	of	a	purine	or	pyrimidine	base	and	a	ribose	or	deoxyribose	
sugar,	the	chemical	unit	is	called	a	nucleoside.	If	a	phosphate	group	is	added	to	the	
nucleoside,	the	molecule	is	now	called	a	nucleotide.
Deoxynucleotide diphosphate
X X
Nucleotide diphosphate
If	a	molecule	is	composed	of	a	purine	or	pyrimidine	base	and	a	ribose	or	deoxyribose	
sugar,	the	chemical	unit	is	called	a	nucleoside.	If	a	phosphate	group	is	added	to	the	
nucleoside,	the	molecule	is	now	called	a	nucleotide.
Dinucleotide Polynucleotide
Organism %A %G %C %T A/T G/C %GC %AT
φX174 24.0 23.3 21.5 31.2 0.77 1.08 44.8 55.2
Maize 26.8 22.8 23.2 27.2 0.99 0.98 46.1 54.0
Octopus 33.2 17.6 17.6 31.6 1.05 1.00 35.2 64.8
Chicken 28.0 22.0 21.6 28.4 0.99 1.02 43.7 56.4
Rat 28.6 21.4 20.5 28.4 1.01 1.00 42.9 57.0
Human 29.3 20.7 20.0 30.0 0.98 1.04 40.7 59.3
Grasshopper 29.3 20.5 20.7 29.3 1.00 0.99 41.2 58.6
Sea	Urchin 32.8 17.7 17.3 32.1 1.02 1.02 35.0 64.9
Wheat 27.3 22.7 22.8 27.1 1.01 1.00 45.5 54.4
Yeast 31.3 18.7 17.1 32.9 0.95 1.09 35.8 64.4
E.	coli 24.7 26.0 25.7 23.6 1.05 1.01 51.7 48.3
La	Regla	
de	
Chargaff
La cromatina es un complejo de macromoléculas de AND, proteína y ARN. 
Sirve para: 
1) Empaquetar el ADN en un volumen muy pequeño 
2) Reforzar el ADN durante la mitosis 
3) Prevenir daños al ADN 
4) Controlar la replicación y la expresión de los genes 
Las proteínas más importantes de la cromatina son las histonas.
La cromatina 
solo se 
encuentra en 
eukariotas
TRANSPOSABLE	
ELEMENTS
The	human	genome	has	
3	billion	bp	and	only	
some	25,000	protein-
coding	genes
85% of genes in dogs have equivalents in humans
http://www.thedogplace.org/Genetics/Congenital-Heritable-Disorders_AVAR.asp#65
https://www.nytimes.com/es/2017/07/20/perros-genes-
lobos-amorosos-amistosos/
Un equipo de investigadores reportó este miércoles en la 
revista Science Advances que la razón por la que los perros 
son así de amorosos sería porque comparten una base 
genética con una enfermedad en los humanos, conocida 
como el síndrome de Williams-Beuren. 
Las personas que padecen ese trastorno de desarrollo, 
causado por la mutación en una región de genes, muestran 
síntomas como la sociabilidad intensa e indiscriminada.
https://www.nytimes.com/es/2017/07/20/perros-genes-
lobos-amorosos-amistosos/
Consanguinidad en poblaciones humanas
Bittles and Black, 2010
https://viagenpets.com/
What	is	CRISPR	
	 In	April	2015,	in	the	first	known	use	of	Crispr	on	
human	embryos,	researchers	led	by	Junjiu	Huang	of	
Sun	Yat-sen	University	in	China	tried	to	correct	a	
defective	gene	that	causes	a	blood	disorder	known	
as	beta	thalassemia.	All	the	embryos	were	unviable	
because	of	a	fatal	defect.
	 	
Gene	Drives
• A	gene	drive	is	a	technique	that	promotes	the	inheritance	of	a	
particular	gene	to	increase	its	prevalence	in	a	population.	
• It	works	only	on	sexually	reproducing	species.	
• An	endonuclease	gene	drives	work	by	cutting	chromosomes	that	do	
not	encode	the	drive	at	a	specific	site,	inducing	the	cell	to	repair	the	
damage	by	copying	the	drive	sequence	onto	the	damaged	
chromosome.
	 	
El	número	de	casos	de	dengue	—una	infección	provocada	por	un	
virus	que	puede	causar	fiebres	hemorrágicas	mortales—	ha	caído	
un	91%	en	un	vecindario	de	Piracicaba	(Brasil)	en	el	que	las	
autoridades	han	liberado	millones	de	mosquitos	transgénicos,	
según	los	datos	del	Servicio	de	Vigilancia	Epidemiológica	de	la	
ciudad,	de	400.000	habitantes.
	 	
In	this	effort	of	synthetic	biology,	a	modified	mevalonate	
pathway	was	used,	and	the	yeast	cells	were	engineered	to	
express	the	enzyme	amorphadiene	synthase	and	a	
cytochrome	P450	monooxygenase	(CYP71AV1),	both	from	
A.	annua.	A	three-step	oxidation	of	amorpha-4,11-diene	
gives	the	resulting	artemisinic	acid.
	
In	nature,	artemisinin	is	produced	by	the	plant	
Artemisia	annua.	The	global	supply	of	artemisinin	
comes	almost	exclusively	from	farmers	that		cultivate	
the	plant.	However,	the	global	supply	of	artemisinin	is	
highly	volatile	because	of	the	uncertainty	associated	
with	crop	success.	
In	2006,	a	team	from	UC	Berkeley	reported	they	had	
engineered	Saccharomyces	cerevisiae	yeast	to	produce	
small	amount	of	the	precursor	artemisinic	acid.	The	
synthesized	artemisinic	acid	can	then	be	transported	
out,	purified	and	chemically	converted	into	artemisinin	
that	they	claim	will	cost	roughly	$0.25	per	dose
	
Schematic	representation	of	the	engineered	
artemisinic	acid	biosynthetic	pathway	in	S.	
cerevisiae	strain	EPY224	expressing	CYP71AV1	
and	CPR.	Genes	from	the	mevalonate	pathway	in	
S.	cerevisiae	that	are	directly	upregulated	are	
shown	in	blue;	those	that	are	indirectly	
upregulated	by	upc2-1	expression	are	in	purple;	
and	the	red	line	denotes	repression	of	ERG9	in	
strain	EPY224.	The	pathway	intermediates	IPP,	
DMAPP	and	GPP	are	defined	as	isopentenyl	
pyrophosphate,	dimethyl	allyl	pyrophosphate	
and	geranyl	pyrophosphate,	respectively.	Green	
arrows	indicate	the	biochemical	pathway	leading	
from	farnesyl	pyrophosphate	(FPP)	to	artemisinic	
acid,	which	was	introduced	into	S.	cerevisiae	
from	A.	annua.	The	three	oxidation	steps	
converting	amorphadiene	to	artemisinic	acid	by	
CYP71AV1	and	CPR	are	shown.