Genetic,	epigenetic	and	exogenetic	information1 Karola	Stotz	and	Paul	Griffiths Abstract We	describe	an	approach	to	measuring	biological	information	where	'information'	is understood	in	the	sense	found	in	Francis	Crick's	foundational	contributions	to molecular	biology.	Genes	contain	information	in	this	sense,	but	so	do	epigenetic	factors, as	many	biologists	have	recognized.	The	term	'epigenetic'	is	ambiguous,	and	we introduce	a	distinction	between	epigenetic	and	exogenetic	inheritance	to	clarify	one aspect	of	this	ambiguity. These	three	heredity	systems	play	complementary	roles	in supplying	information	for	development. We	then	consider	the	evolutionary	significance	of	the	three	inheritance	systems.	Whilst the	genetic	inheritance	system	was	the	key	innovation	in	the	evolution	of	heredity,	in modern	organisms	the	three	systems	each	play	important	and	complementary	roles	in heredity	and	evolution. Our	focus	in	the	earlier	part	of	the	paper	is	on	'proximate	biology',	where	information is	a	substantial	causal	factor	that	causes	organisms	to	develop	and	causes	offspring	to resemble	their	parents.	But	much	philosophical	work	has	focused	on	information	in 'ultimate	biology'.	Ultimate	information	is	a	way	of	talking	about	the	evolutionary design	of	the	mechanisms	of	development	and	inheritance.	We	conclude	by	clarifying the	relationship	between	the	two.	Ultimate	information	is	not	a	causal	factor	that	acts in	development	or	heredity,	but	it	can	help	to	explain	the	evolution	of	proximate information,	which	is. 1	In:	Routledge	Handbook	of	Evolution	and	Philosophy,	section	"Evolution	and Information" 1.	Introduction The	most	popular	account	of	genetic	information	in	contemporary	philosophy	is 'teleosemantics'	(Millikan	1984;	Maynard	Smith	2000;	Shea	2007a). This	yields	a semantic	notion	of	information	–	the	information	in	a	gene	is	a	description	or	an instruction	and	as	such	genetic	information	can	be	true	or	false,	obeyed	or disobeyed.	It	also	defines	the	information	content	of	a	gene	in	terms	of	the evolutionary	history	of	that	gene.	Physically	identical	genes	can	have	entirely different	information	content	if	they	evolved	due	to	different	selective	pressures. This	way	of	thinking	about	genetic	information	corresponds	closely	to	the	image	of genes	in	popular	science.	Genes	are	coded	messages	instructing	organisms	to develop	in	one	way	or	another,	and	those	instructions	were	written	by	evolution. But	the	teleosemantic	approach	fails	to	meet	two	obvious	desiderata	for	an	account of	genetic	information.	First,	genetic	information	ought	to	feature	in	causal explanations	of	developmental.	But	the	historical	nature	of	teleosemantic information	means	that	the	information	content	of	a	gene	can	be	changed	or removed	altogether	without	any	effect	on	how	the	organism	develops	(Griffiths 2013):	teleosemantic	information	is	causally	inert.	Second,	heredity	is	usually thought	to	be	a	precondition	of	evolution	by	natural	selection	and	heredity	is	widely supposed	to	involve	the	transmission	of	genetic	information.	Teleosemantics,	in contrast,	implies	that	the	evolution	of	any	novel	character	begins	without	any genetic	information	about	that	character	being	present.	The	genes	that	influence	a character	only	carry	information	about	it	after	that	character	has	evolved	by	natural selection	acting	on	those	genes.	We	return	to	teleosemantics	at	the	end	of	the chapter	and	discuss	how	it	may	play	a	role	in	'ultimate	biology'	that	complements other	notions	of	genetic	information	in	'proximate	biology'.	For	now,	however,	our focus	will	be	on	a	strictly	proximate	sense	of	genetic	information	–	a	sense	in	which that	information	plays	a	substantive	causal	role	in	the	operation	of	living	systems. 2.	Genetic	information:	Crick	and	informational	specificity If	there	is	one	thing	all	philosophers	who	have	written	about	genetic	information agree	on	it	is	that	genetic	information	is	not	merely	the	application	of	Shannon's information	theory	to	biological	systems.	Many	components	of	any	physical	system will	contain	mutual	information	about	one	another	merely	in	virtue	of	the	fact	that they	form	part	of	a	causal	network.	But	the	fact	that	genes	are	'informational molecules'	is	meant	to	be	distinctive,	something	that	marks	systems	with	a	genome out	from	other	chemical	systems	and	also	marks	genes	out	from	many	other components	of	living	systems	(Maynard	Smith	2000;	Godfrey-Smith	2000;	Sarkar 2005;	Shea	2007b;	Bergstrom	and	Rosvall	2009;	Stegmann	2014). In	the philosophical	literature,	claiming	that	genetic	information	is	merely	Shannon information	has	been	a	way	to	minimise	its	theoretical	importance	(Sterelny	and Griffiths	1999;	Griffiths	2001). In	our	view	there	is	something	distinctive	about	genetic	information,	but	it	is	a distinctive	property	best	captured	using	the	Shannon	formalism.	It	is	a	property	first clearly	identified	by	Francis	Crick	in	the	period	of	the	mid-20th	century	when,	it	is generally	agreed,	molecular	biology	became	an	informational	science	(Kay	2000). Although	Watson	and	Crick	had	used	the	term	'genetic	information'	earlier,	the	first substantial	use	is	in	Crick's	1958	statement	of	the	Sequence	Hypothesis	and	Central Dogma,	some	of	the	most	influential	ideas	in	the	history	of	molecular	biology: The	Sequence	Hypothesis ...	In	its	simplest	form	it	assumes	that	the	specificity	of	a	piece	of	nucleic	acid	is expressed	solely	by	the	sequence	of	its	bases,	and	that	this	sequence	is	a (simple)	code	for	the	amino	acid	sequence	of	a	particular	protein.	... The	Central	Dogma This	states	that	once	'information'	has	passed	into	protein	it	cannot	get	out again.	In	more	detail,	the	transfer	of	information	from	nucleic	acid	to	protein may	be	possible,	but	transfer	from	protein	to	protein,	or	from	protein	to nucleic	acid	is	impossible.	Information	means	here	the	precise	determination of	sequence,	either	of	bases	in	the	nucleic	acid	or	of	amino-acid	residues	in	the protein.	(Crick	1958,	152-3	italics	in	original) Here	Crick	identifies	the	specificity	of	a	gene	for	its	product	with	the	information coded	in	the	sequence	of	the	gene.	By	doing	so,	he	linked	the	idea	of	information very	closely	to	one	of	the	fundamental	organizing	concepts	of	biology.	Biological specificity	is	nothing	less	than	the	"orderly	patterns	of	metabolic	and	developmental reactions	giving	rise	to	the	unique	characteristics	of	the	individual	and	of	its	species" (Kleinsmith	2014).	From	the	second	half	of	the	19th	to	the	first	half	of	the	20th century	specificity	was	"the	thematic	thread	running	through	all	the	life	sciences" (Kay	2000,	41),	starting	with	botany,	bacteriology,	immunology	and	serology. Specificity	came	to	be	understood	in	terms	of	the	complementary	three-dimensional shapes	of	biomolecules	that	exhibit	specificity	for	one	another.	By	mid-century quantum	mechanics	had	provided	the	necessary	insight	to	explain	the	observed structural	complementarity	between	molecules	in	terms	of	the	quantum-physical forces	that	allow	biomolecules	to	form	weak	hydrogen	bonds	with	one	another. Crick	introduced	a	new,	more	abstract	conception	of	specificity	in	terms	of	how	one molecule	can	precisely	specify	the	linear	structure	of	another.	It	is	the	colinearity between	DNA,	RNA	and	amino	acid	chains	that	embodies	specificity.	The information	that	specifies	the	product	is	no	longer	carried	by	a	three-dimensional structure	but	instead	by	the	linear,	one-dimensional	order	of	elements	in	each sequence.	Amongst	other	consequences,	this	means	that	specificity	becomes independent	of	the	medium	in	which	this	order	is	expressed	(i.e.	DNA,	RNA	or amino	acid	chain)	and	of	the	kind	of	reaction	by	which	the	specificity	is	transmitted (i.e.	transcription	or	translation).	The	same	information/specificity	flows continuously	through	these	three	media	and	through	both	processes. According	to	Crick	the	process	of	protein	synthesis	involves	"the	flow	of	energy,	the flow	of	matter,	and	the	flow	of	information."	While	he	noted	the	importance	of	the "exact	chemical	steps",	he	clearly	separated	this	flow	of	matter	and	energy	from what	he	regarded	as	"the	essence	of	the	problem",	namely	the	problem	of	how	to join	the	amino	acids	in	the	right	order.	The	flow	of	"hereditary	information",	defined as	"the	specification	of	the	amino	acid	sequence	of	the	protein",	solved	this	critical problem	of	"sequentialization"	(Crick	1958,	143-144).	This	conception	of information	primarily	offered	Crick	a	way	to	reduce	the	transfer	of	specificity	from	a three-dimensional	to	a	one-dimensional	problem	by	abstracting	away	from	the biochemical	and	material	connotations	of	specificity. In	"Central	Dogma	of	Molecular	Biology"	Crick	clarified	his	earlier	position: The	two	central	concepts	which	had	been	produced	...	were	those	of	sequential information	and	of	defined	alphabets.	Neither	of	these	steps	was	trivial.	...	This temporarily	reduced	the	central	problem	from	a	three	dimensional	one	to	a one	dimensional	one.	...	The	principal	problem	could	then	be	stated	as	the formulation	of	the	general	rules	for	information	transfer	from	one	polymer with	a	defined	alphabet	to	another.(Crick	1970,	561) The	philosopher	Gregory	Morgan2	corresponded	with	Crick	late	in	his	career	about the	original	inspiration	for	using	the	term	'information'.	This	1998	correspondence shows	the	consistency	of	Crick's	view	over	forty	years.	He	states	that	'information' was	"merely	a	convenient	shorthand	for	the	underlying	causal	effect",	namely	the "precise	determination	of	sequence".	Information	for	him	meant	only	"detailed residue-by-residue	determination". 2	Personal	communication.	We	are	extremely	grateful	to	Morgan	for	making	Crick's	replies	of	March 20	and	April	3	1998	available	to	us. Amongst	the	many	virtues	of	Crick's	conception	of	information	as	the	encoding	of specificity	through	the	precise	determination	of	the	sequence	of	gene	products	is that	it	can	be	made	precise	using	information-theoretic	tools.	In	the	next	section	we show	how	this	is	done.	In	the	subsequent	sections	we	show	that	the	resulting measure	of	'Crick	information'	can	be	applied	to	a	wider	range	of	components	of biological	systems	than	Crick	himself	supposed. 3.	Information,	biological	specificity	and	causal	specificity Crick	identified	information	with	the	encoding	of	biological	specificity.	Rather	than rest	with	an	intuitive	notion	of	specificity	we	can	make	the	idea	precise.	An important	earlier	effort	to	do	so	by	Sahotra	Sarkar	proposed	that	one	variable	is	a biologically	specific	cause	of	another	if	there	is	a	bijective	mapping	between	the values	of	the	variables.	Each	value	of	the	first	variable	corresponds	to	one	and	only one	value	of	the	other	variable,	and	vice-versa	(Sarkar	2005,	267).	This	analysis	of biological	specificity	is	identical	to	the	analysis	of	a	broader	notion,	'causal specificity',	given	independently	by	James	Woodward	(2010).	According	to Woodward,	a	causal	relationship	is	more	specific	to	the	extent	that	it	enables	finegrained	control	of	the	value	of	the	effect	variable	via	manipulation	of	the	cause variable.	In	the	limiting	case,	there	is	a	bijective	mapping	between	the	two	sets	of values.	It	seems	clear	that	both	authors	are	dealing	with	same	idea	–	biological specificity	is	simply	the	application	of	causal	specificity	to	biological	systems. Woodward's	account	of	causal	specificity	is	part	of	a	larger	program	to	analyse	the idea	of	causation	as	it	figures	in	the	practice	of	the	special	sciences,	including biology	(Woodward	2003;	Woodward	2014).	According	to	this	'interventionist'	or 'manipulationist'	view	of	causation	two	variables	are	causally	related	if	it	is	possible to	manipulate	the	value	of	one	by	intervening	on	the	other.	In	the	limiting	case, variables	are	causally	related	if	there	is	a	single	pair	of	values	of	each	variable	that are	related	in	this	way,	even	if	the	two	are	unrelated	across	the	rest	of	their	ranges. Clearly,	then,	the	interventionist	theory	of	causation	needs	to	differentiate	between causes	in	various	ways-to	identify	ones	that	"are	likely	to	be	more	useful	for	many purposes	associated	with	manipulation	and	control	than	less	stable	relationships" (Woodward	2010,	315).	A	number	of	different	ways	to	distinguish	types	of	causes have	been	suggested,	and	one	of	these	is	causal	specificity. The	intuitive	idea	is	that	interventions	on	a	highly	specific	causal	variable	C	can	be used	to	produce	any	one	of	a	large	number	of	values	of	an	effect	variable	E, providing	what	Woodward	terms	'fine-grained	influence'	over	the	effect	variable (Woodward	2010,	302).	In	earlier	work	we	and	our	collaborators	have	developed	an information-theoretic	framework	in	which	to	measure	the	specificity	of	causal relationships	within	the	interventionist	account	(Griffiths	et	al.	2015b).	Our proposal	formalizes	the	simple	idea	that	the	more	specific	the	relationship	between a	cause	variable	and	an	effect	variable,	the	more	information	we	will	have	about	the effect	after	we	perform	an	intervention	on	the	cause.	This	led	us	to	propose	a	simple measure	of	specificity: SPEC:	the	specificity	of	a	causal	variable	is	obtained	by	measuring	how	much	mutual information	interventions	on	that	variable	carry	about	the	effect	variable3 Specificity	measures	the	mutual	information	between	interventions	on	C	and	the variable	E.	This	is	not	a	symmetrical	measure	because	the	fact	that	interventions	on C	change	E	does	not	imply	that	interventions	on	E	will	change	C.	Formally, I(C; E) ≠ I(E; C),	where	I	is	mutual	information	and	C	is	read	'do	C'	and	means	that the	value	of	C	results	from	an	intervention	on	C	(Pearl	2009). This	measure	adds	precision	to	several	aspects	of	the	interventionist	account	of causation.	Any	two	variables	that	satisfy	the	interventionist	criterion	of	causation 3	This	measure	is	not	defined	without	a	probability	distribution	over	the	cause. (Griffiths	et	al.	2015)	suggests	that	SPEC	with	a	maximum	entropy	distribution	over C	measures	the	degree	of	causal	control	that	C	has	over	E. SPEC	with	an	actual distribution	over	C	measures	the	extent	to	which	C	causally	explains	the	observed values	of	E	in	that	specific	data. will	show	some	degree	of	mutual	information	between	interventions	and	effects. This	criterion	is	sometimes	called	'minimal	invariance'	–	there	are	at	least	two values	of	C	such	that	a	manipulation	of	C	from	one	value	to	the	other	changes	the value	of	E.	If	the	relationship	C → E	is	minimally	invariant,	that	is,	invariant	under	at least	one	intervention	on	C,	then	C	has	some	specificity	for	E,	that	is,	I(C; E) > 0 (Griffiths	et	al.	2015a) We	propose	that	causal	relationships	in	biological	systems	can	be	regarded	as informational	when	they	are	highly	causally	specific.	Biological	specificity,	whether stereochemical	or	informational,	seems	to	us	to	be	simply	the	application	of	the	idea of	causal	specificity	to	biological	systems.	The	remarkable	specificity	of	reactions	in living	systems	that	biology	has	sought	to	explain	since	the	late	C19th	can	equally	be described	as	the	fact	that	living	systems	exercise	'fine	grained	control'	over	many variables	within	those	systems.	Organisms	exercise	fine-grained	control	over	which substances	provoke	an	immune	response	through	varying	the	stereochemistry	of recognition	sites	on	antibodies	for	antigens.	They	catalyze	very	specific	reactions through	varying	the	stereochemical	affinity	of	enzymes	for	their	substrates,	or	of receptors	for	their	ligands.	Organisms	reproduce	with	a	high	degree	of	fidelity through	the	informational	specificity	of	nucleic	acids	for	proteins	and	functional RNAs.	Genes	are	regulated	in	a	highly	specific	manner	across	time	and	tissue through	the	regulated	recruitment	of	trans-acting	factors	and	the	combinatorial control	of	gene	expression	and	post-transcriptional	processing	by	these	factors	and the	cis-acting	sites	to	which	they	bind.	These	are	all	important	aspects	of	why	living systems	appear	to	be	'informed'	systems,	and	what	is	distinctive	about	all	these processes	is	that	they	are	highly	causally	specific. 4.	Genetics	and	epigenetics:	Two	sources	of	causal	specificity Elsewhere	we	have	termed	the	encoding	of	specificity	for	the	structure	of biomolecules	'Crick	information'	(Griffiths	and	Stotz	2013).	If	a	cause	makes	a specific	difference	to	the	linear	sequence	of	a	biomolecule,	it	contains	Crick information	for	that	molecule.	This	definition	embodies	the	essential	idea	of	Crick's sequence	hypothesis,	without	in	principle	limiting	the	location	of	information	to nucleic	acid	sequences	as	Crick	does.	Our	definition	of	Crick	information	can	be applied	to	other	causal	factors	that	affect	the	structure	of	biomolecules. Crick's	Central	Dogma	and	Sequence	Hypothesis	were	based	on	a	very	simple picture	of	how	the	specificity	of	biomolecules	is	encoded	in	living	cells.	They	assume that	the	sequence	of	the	gene	not	only	precisely	determines	the	sequence	of	the product,	but	also	completely	determines	it.	We	now	know	that	in	eukaryotes	coding regions	are	surrounded	by	a	large	number	of	non-coding	sequences	that	regulate gene	expression.	The	large	discrepancy	between	the	number	of	coding	sequences and	the	number	of	gene	products	lead	to	the	insight	that	the	informational specificity	in	coding	regions	of	DNA	must	be	amplified	by	other	biomolecules	in order	to	specify	the	whole	range	of	products.	'Precise	determination'	implies	a	oneto-one	relationship,	and	if	we	focus	on	coding	sequences	alone,	we	find	a	one-tomany	relationship	between	sequence	and	product.	This	means	that	additional specificity	of	a	kind	not	captured	by	the	original	sequence	hypothesis	is	required. Different	mechanisms	of	gene	regulation	co-specify	the	final	linear	product	of	the gene	in	question,	first	by	activating	the	gene	so	it	can	get	transcribed,	second	by selecting	a	chosen	subset	of	the	entire	coding	sequence	(e.g.	alternative	splicing), and	thirdly	by	creating	new	sequence	information	through	the	insertion,	deletion	or exchange	of	single	nucleotide	letters	of	the	RNA	(e.g.	RNA	editing).	Thus	specificity, and	hence	Crick	information,	is	distributed	between	a	range	of	factors	in	addition	to the	original	coding	sequence:	DNA	sequences	with	regulatory	functions,	diverse gene	products	such	as	transcription,	splicing	and	editing	factors	(usually	proteins), and	non-coding	RNAs	(Stotz,	2006).	Biologists	today	in	this	field	search	for	the 'target	sequence	specificity'	of	forms	of	editing	(Davidson	2002),	or	search	for 'missing	information'	seen	in	a	specific	splice	variant,	supplementing	the information	present	in	the	coding	sequence	to	determine	a	specific	outcome	(Wang and	Burge	2008). Absolute	specificity	turns	out	to	be	not	inherent	in	any	single	biomolecule	in	these molecular	networks	but	induced	by	regulated	recruitment	of	many	molecules	and combinatorial	control	of	transcription	and	post-transcriptional	processing	by	those molecules	(Ptashne	and	Gann	2002).	And	it	is	here	that	we	will	find	that	the networks	cannot	be	reduced	to	DNA	sequences	plus	gene	products,	because	many	of the	latter	need	to	be	recruited,	activated	or	transported	to	render	them	functional. The	recruitment,	activation	or	transportation	of	transcription,	splicing	and	editing factors	allows	the	environment	to	have	specific	effects	on	gene	expression.	Some gene	products	serve	to	relay	environmental	(Crick)	information	to	the	genome.	Not just	morphogenesis	at	higher	levels	of	organisation,	but	even	the	determination	of the	primary	sequence	of	gene	products	is	a	process	of	'molecular	epigenesis'	that cannot	be	reduced	to	the	information	encoded	in	the	genome	alone	(Stotz	2006; Griffiths	and	Stotz	2013). Eva	Jablonka	and	Marion	Lamb	were	amongst	the	first	biological	theorists	to	see	the full	significance	of	epigenetics	for	understanding	biological	information.	They	wrote that	"DNA	is	not	just	a	passive	information	carrier,	it	is	also	a	responsive	system" (Jablonka	and	Lamb	1995,	2).	But	this	insight	has	older	roots.	In	an	immediate response	to	Crick's	new	picture	of	sequential	information	coded	in	DNA,	the	ciliate biologist	David	L.	Nanney	pointed	out	that: This	view	of	the	nature	of	the	genetic	material	...	permits,	moreover,	a	clearer conceptual	distinction	than	has	previously	been	possible	between	two	types	of cellular	control	systems.	On	the	one	hand,	the	maintenance	of	a	"library	of specificities,"	both	expressed	and	unexpressed,	is	accomplished	by	a	template replicating	mechanism.	On	the	other	hand,	auxiliary	mechanisms	with different	principles	of	operation	are	involved	in	determining	which specificities	are	to	be	expressed	in	any	particular	cell.	...To	simplify	the discussion	of	these	two	types	of	systems,	they	will	be	referred	to	as	"genetic systems"	and	"epigenetic	systems".	(D.	L.	Nanney	1958,	712) What	is	remarkable	about	Nanney's	discussion	is	the	rapidity	with	which	he	realised that	the	new	view	of	the	gene	proposed	by	Crick	implied	the	necessity	for	something like	the	epigenetic	mechanisms	that	have	since	been	uncovered. Nanney hypothesized	that	the	utility	of	epigenetic	control	systems	"lies	precisely	in	their ability	to	respond	specifically	to	altered	environmental	conditions"	and	suggested that	the	influence	of	these	systems	should	be	understood	in	terms	their	"specificity of	induction"	of	developmental	effects	(Nanney	1958,	713	and	715)4.	Elsewhere Nanney	likened	them	to	"signal	interpreting	devices,	yielding	predictable	results	in response	to	specific	stimuli	from	inside	and	outside	the	cell"	(David	L.	Nanney	1959, 333)	.	Griffiths	and	Stotz	(2013)	have	argued	that	epigenetic	factors	relay environmental	signals	to	the	genome,	very	much	in	line	with	Nanney's	idea	of	them as	interpreting	devices. The	existence	of	two	sources	of	developmental	information	implies	that	heredity needs	to	provide	both	genetic	and	epigenetic	information	if	it	is	to	reproduce	living systems.	In	the	following	sections	we	make	some	distinctions	between	different senses	of	'epigenetic'	and	explore	the	complementary	roles	of	the	different	forms	of biological	information. 5.	Epigenetic	and	Exogenetic	inheritance Epigenesis	is	the	ancient	idea	that	the	outcomes	of	biological	development	are created	during	the	process	of	development,	not	preformed	in	the	inputs	to development.	In	earlier	centuries,	epigenesis	was	contrasted	to	the	'preformationist' 4	In	line	with	this	additional	understanding	of	specificity	Woodward	(2010,	304-5) has	added	the	"dependencies	of	the	time	and	place	of	occurrence	of	E	on	the	time and	place	of	C"	to	the	"systematic	dependencies	between	a	range	of	different possible	states	of	the	cause	and	different	possible	states	of	the	effect". view	that	organisms	already	exist	in	miniature	within	sperm	or	ova	(Roe	1981). Evolutionary	developmental	biologist	Brian	Hall	notes	that,	"As	a	continuation	of	the concept	that	development	unfolds	and	is	not	preformed	(or	ordained),	epigenetics	is the	latest	expression	of	epigenesis"(Hall	2011,	12). The	related	term	'epigenetics'	was	introduced	by	Conrad	H.	Waddington	in	a	broad sense	that	is	almost	synonymous	with	development	(Waddington	1940; Waddington	1942).	Epigenetics	was	the	study	of	the	causal	processes	by	which many	genes	interact	with	one	another	and	with	many	environmental	factors	to produce	an	organism. Today,	however,	most	biologists	understand	the	term	in	a narrower	sense,	ultimately	derived	from	the	work	of	Nanney	quoted	above	(D.	L. Nanney	1958;	Haig	2004).	In	this	narrower	sense,	epigenetics	is	the	study	of	the mechanisms	that	determine	which	genome	sequences	will	be	expressed	in	a	cell	and how	they	will	be	expressed.	Epigenetic	mechanisms	control	cell	differentiation	in multicellular	organisms,	or	the	life	cycle	of	unicellular	organisms.	Epigenetic mechanisms	give	cells	their	identity	as	cells	of	a	particular	type.	When	epigenetic modifications	are	maintained	through	mitosis	this	produces	cell-line	heredity. This	ambiguity	in	the	term	'epigenetic'	itself	is	relatively	unproblematic,	but	it produces	a	genuinely	confusing	ambiguity	when	biologists	talk	of	'epigenetic inheritance'.	In	the	narrow	sense	of	'epigenetic'	there	is	epigenetic	inheritance	only in	cases	when	a	methylation	pattern,	chromatin	modification	or	the	like	is transmitted	through	the	germline	from	one	generation	to	the	next.	That	is	to	say, when	the	mechanisms	that	make	cell	identity	mitotically	heritable,	between	cell generations,	also	make	some	aspect	of	cell	identity	meiotically	heritable,	between generations	of	whole	organisms.	However,	the	term	'epigenetic	inheritance'	is	often meant	far	more	broadly,	to	include	every	mechanism	by	which	parents	can	influence the	phenotypes	of	their	offspring	other	than	through	the	inheritance	of	nuclear	DNA. To	avoid	confusion	we	have	suggested	referring	to	this	broader	class	of	mechanisms as	'exogenetic	inheritance'	(Griffiths	and	Stotz	2013,	Ch.	5).	This	leaves	us	with	three categories	of	inheritance:	genetic,	epigenetic	and	exogenetic,	each	of	which	is	a source	of	information	for	the	developing	organism. In	a	similar	vein	Jablonka	and	Lamb	have	attempted	to	organize	inheritance	around four	'dimensions'	of	heredity:	Genetic,	Epigenetic,	Behavioral	(including	Ecological and	Cultural),	and	Symbolic	(Jablonka	and	Lamb	2005).	The	Genetic	Inheritance System	comprises	the	underlying	base	sequence	of	the	genome.	The	Epigenetic Inheritance	System	includes	chromatin	modifications	plus	other	developmental resources	that	are	transmitted	through	the	cytoplasm	of	the	egg,	such	as	parental gene	products.	Jablonka	and	Lamb	also	include	within	epigenetic	inheritance	the cortical	(cytoplasmic)	inheritance	system,	consisting	of	cellular	structures	such	as organelles	with	their	own	membranes	and	genes	(mitochondria	and	chloroplasts), membrane-free	organelles	(ribosomes	and	the	Golgi	apparatus),	and	the	cellular membrane	systems.	All	these	structures	cannot	be	re-produced	from	genetic information	but	act	as	templates	for	themselves.	The	Behavioral	Inheritance	System (including	ecological	and	cultural	inheritance)	forms	their	third	dimension,	in	which information	is	transmitted	through	behavior-influencing	substances,	non-imitative and	imitative	social	learning,	as	well	as	habitat	construction,	food	provisioning,	and other	parental	effects.5	The	fourth	and	last	dimension	is	the	Symbolic	Inheritance System.	Offspring	in	some	species	inherit	social	structures	and	rules,	cultural traditions	and	institutions,	and	technologies.	This	inheritance	system	importantly includes	epistemic	tools,	such	as	language,	competent	adults,	teaching	techniques etc.	These	four	systems	use	different	mechanisms	of	transmission	and	show changing	degrees	of	fidelity.	Some	mechanisms	may	not	be	intrinsically	stable	from one	generation	to	the	next.	But	even	the	nuclear	genetic	inheritance	system,	for example,	relies	on	several	layers	of	proof	reading	and	copy-error	detection	systems for	its	exceptionally	high	fidelity.	A	suitable	mechanism	of	scaffolding	can	lend	a 5	Jablonka	and	Lamb	do	not	explicitly	mention	or	analyse	the	status	of	the experience-dependent	epigenetic	inheritance	that	often	mediates	behavioral inheritance,	and	which	creates	an	intimate	connection	between	their	second	and	the third	dimension.	See	below. transmission	mechanism	reliability:	proof	reading	supports	genetic	inheritance, epigenetics	stabilizes	gene	expression.	Learning	is	scaffolded	by	teaching	or	by	the reliable	affordances	of	stimuli	"that	define	what	is	available	to	be	learned...[and]... function	to	channel	malleability	into	stable	trajectories"	(West,	King,	and	White 2003,	618). To	add	to	the	confusion,	epigenetic	mechanisms	are	involved	in	the	production	of exogenetic	inheritance	as	well	as	in	epigenetic	inheritance	in	the	narrow	sense	just defined!	Many	forms	of	exogenetic	inheritance,	be	that	behavioral,	social	or	cultural, are	mediated	by	epigenetic	inheritance.	The	epigenetic	modifications	in	question	do not	pass	through	the	germline	but	are	reconstructed	anew	in	each	generation.	Some call	these	"transgenerational	epigenetic	effects"	(Youngson	and	Whitelaw	2008),	or "experience-dependent	epigenetic	inheritance"	(Danchin	et	al.	2011).	Despite involving	epigenetic	mechanisms	these	are	examples	of	exogenetic	heredity	because the	epigenetic	marks	are	not	inherited	by	one	cell	from	another,	but	reestablished	in the	second	cell	via	an	environmental	influence	(often	reliably	produced	by	a	parent). In	one	well-studied	example,	epigenetic	mechanisms	have	been	shown	to	mediate the	behavioral	inheritance	of	maternal	care	behavior	and	stress	reactivity	in	rats. Maternal	behavior	in	the	form	of	licking	and	grooming	establishes	stable	patterns	of methylation	in	certain	genes	in	the	pups'	hippocampus.	These	affect	gene	expression and	therefore	brain	development,	with	downstream	effects	on	the	behavior	of	the next	generation	of	mother	rats.	The	behavior	of	these	second-generation	mothers reestablishes	the	patterns	of	methylation	in	her	pups.	But	the	actual	patterns	of methylation	are	not	inherited	by	offspring	cells	from	maternal	cells	(Meaney	2001). The	new	mothers'	behavior	is	to	a	certain	extent	malleable	to	environmental changes;	however,	her	epigenetic	gene	expression	pattern	predisposes	her	strongly to	resemble	the	behavior	of	her	mother.	An	interesting	factor	to	note	here	is	that	the parent-offspring	correlations	created	through	these	transgenerational	epigenetic effects	are	often	much	higher	than	those	observed	in	narrow-sense	epigenetic inheritance,	as	in	the	famous	case	of	the	agouti	mouse	(Wolff	et	al.	1998). There	is	no	uniquely	correct	way	to	group	the	many	different	mechanisms	of heredity,	and	Jablonka	and	Lamb's	four-part	taxonomy	has	much	to	recommend	it. Nevertheless,	for	our	purposes	we	prefer	a	simpler,	three-way	taxonomy:	genetic, epigenetic	(meiotic	cell-line	heredity),	and	exogenetic. 6.	The	evolutionary	significance	of	genetic,	epigenetic	and	exogenetic inheritance Evolutionary	biologist	Adam	S.	Wilkins	gives	a	clear	statement	of	a	conventional view	about	the	evolutionary	significance	of	epigenetic	inheritance: If	an	epimutation	is	to	have	evolutionary	importance,	it	must	persist.	...	This matter	is	central	to	whether	epimutations	can	be	treated	as	equivalent	to conventional	mutations	or	whether,	if	they	have	some	degree	of	stability,	some new	population	genetic	theory	is	needed.	(Wilkins	2011,	391) Some	cases	certainly	meet	this	criterion.	In	a	comprehensive	review	of transgenerational	epigenetic	inheritance	Jablonka	and	Raz	conclude	that	epigenetic inheritance	is	ubiquitous,	and	has	been	shown	to	persist	for	up	to	3	generations	in humans	and	up	to	8	generations	in	other	animal	taxa	(Jablonka	and	Raz	2009).	In plants,	which	lack	comprehensive	reprogramming	of	DNA	in	each	generation,	the stability	of	epigenetic	inheritance	can	rival	genetic	inheritance.	Many	cases	of	true epigenetic	inheritance,	particularly	in	mammals,	would	however	not	meet	the criterion	of	multi-generational	stability.	Such	cases	may	also	disappoint	with	respect to	their	efficiency	or	fidelity	of	transmission,	resulting	in	much	lower	parentoffspring	correlation	than	genetic	inheritance. However,	it	is	simply	not	correct	that	epigenetic	change	will	only	affect	evolution	if the	changes	themselves	persist	for	more	than	one	generation.	In	conventional quantitative	genetics,	the	importance	of	genetics	is	not	that	individual	genes	can	be tracked	from	one	generation	to	the	next	–	quantitative	genetics	does	not	do	this	– but	that	Mendelian	assumptions	let	us	work	out	what	phenotypes	(and	hence fitnesses)	will	appear	in	the	next	generation	as	a	function	of	the	phenotypes	in	the last	generation. Epigenetic	and	exogenetic	inheritance	both	change	this	mapping from	parental	phenotype	to	offspring	phenotype,	and	therefore	affect	evolution. Both	epigenetic	and	exogenetic	inheritance	appear	in	quantitative	genetics	as 'parental	effects':	correlations	between	parent	and	offspring	phenotypes	above	and beyond	correlations	between	parent	and	offspring	genotypes,	which	are	also	not	the result	of	a	shared	environment	independently	influencing	both	parent	and	offspring. It	has	long	been	understood	that	one-generation	parental	effects	can	substantially alter	the	dynamics	of	evolutionary	models,	and	change	which	state	a	population	will evolve	to	as	an	equilibrium	(Lande	and	Price	1989)(Wade	1998).	The	argument	that epigenetic	inheritance	needs	to	be	stable	for	several	generations	to	have evolutionary	significance	appears	to	be	a	non-sequitur. Although	all	three	forms	of	heredity	have	evolutionary	significance,	this	does	not mean	that	they	have	the	same	evolutionary	significance.	Epigenetic	marks	are sensitive	to	environmental	factors	in	that	they	are	first	"established	by	transiently expressed	or	transiently	activated	factors	that	respond	to	environmental	stimuli, developmental	cues,	or	internal	events"	(Bonasio,	Tu,	and	Reinberg	2010,	613). Hence	epigenetic	variations	may,	indeed,	be	less	stable	than	genetic	ones,	because they	are	in	principle	reversible	by	the	same	mechanisms	that	induced	them.	This may	make	them	more	adaptive	in	variable	environmental	conditions	than	genetic variation	(Jablonka	and	Lamb	1995;	Holliday	2006).	Many	hypotheses	about	the evolutionary	origins	of	epigenetic	inheritance	stress	its	value	in	spatially	and temporally	heterogenous	environments,	where	it	allows	rapid	responses	to	change. This	kind	of	rapid	heritable	response	is	sometimes	referred	to	as	transgenerational adaptive	plasticity. All	three	forms	of	heredity	provide	information	for	development	in	the	precise sense	outlined	above.	But	the	widely	held	view	that	genetic	inheritance	is	somehow more	basic	than	epigenetic	or	exogenetic	inheritance,	and	that	nucleic	acids	are distinctively	'informational	molecules',	is	not	without	foundation. With	the exception	of	some	forms	of	structural	heredity	such	as	the	membrane	inheritance system,	epigenetic	inheritance	works	by	modifying	the	expression	of	coding sequences.	It	amplifies	the	amount	of	Crick	information	in	the	genome	by	enabling	a greater	range	of	biomolecules	to	be	specified	from	the	same	set	of	nucleic	acid templates.	The	same	can	be	said	of	some	exogenetic	inheritance	mechanisms.6	So both	epigenetic	and	some	exogenetic	inheritance	can	reasonably	be	thought	of	as systems	for	the	hereditary	regulation	of	genome	expression.	At	the	heart	of	these heredity	systems,	then,	is	the	ability	of	nucleic	acids	to	provide	templates	for	the synthesis	of	biomolecules.	The	evolutionary	breakthrough	that	came	with	nucleic acid	heredity	was	the	provision	of	"a	sequestered	molecular	template	used	by	cells to	transfer	specificities	to	subsequent	(cellular)	generations"	(Sarkar	2005,	94).	This insight	can	be	usefully	combined	with	another,	namely	that	the	way	in	which	Crick information	is	encoded	in	nucleic	acid	templates	bears	many	of	the	hallmarks	of	a well-designed	Shannon	information	channel	(Bergstrom	and	Rosvall	2009).	Nucleic acid	heredity	is	a	key	innovation	in	the	history	of	life	that	allowed	the	highly efficient	transfer	of	large	quantities	for	Crick	information	from	one	cell	to	the	next. The	mistake	made	by	many	authors	who	have	tried	to	identify	the	special	role	of nucleic	acid	in	heredity,	it	seems	to	us,	has	been	to	focus	on	the	relative	importance of	different	heredity	systems	in	enabling	future	evolution,	rather	than	this foundational	role	of	nucleic	acid	heredity	in	the	history	of	life. A	related	error	is	to	identify	the	special	role	of	nucleic	acids	in	heredity	with	the	idea that	a	greater	proportion	of	developmental	information	flows	through	the	genetic heredity	channel	than	through	epigenetic	or	exogenetic	channels.	This	idea	is associated	with	attacks	on	the	'parity	thesis,'	"according	to	which	the	roles	played by	the	many	causal	factors	that	affect	development	do	not	fall	neatly	into	two 6	But	not	all.	Exogenetic	inheritance	includes	cultural	and	symbolic	inheritance, which	are	not	primarily	about	selecting	or	amplifying	the	specificity	in	nucleic	acid coding	sequences	(see	Stotz	and	Allen	2012). kinds,	one	exclusively	played	by	DNA	elements	the	other	exclusively	played	by non-DNA	elements"	(Griffiths	and	Gray	2005,	420; see	also	Griffiths	and	Knight 1998).	One	consequence	of	parity	is	that	"Any	defensible	definition	of	information	in developmental	biology	is	equally	applicable	to	genetic	and	non-genetic	causal factors	in	development"	(Griffiths	2001,	396; see	also	Griffiths	and	Gray	1994).	Our approach	to	information	in	this	chapter	clearly	meets	this	constraint,	which	was inspired	by	Susan	Oyama's	calls	for	'parity	of	reasoning'	in	nature/nurture	disputes (Oyama	2000	and	elsewhere).	Critics	have	responded	to	the	parity	idea	by	admitting that	non-genetic	causes	can	in	principle	carry	information,	but	insisting	that	far more	information	is	carried	by	genes	(Sterelny,	Dickison,	and	Smith	1996;	Waters 2007;	Shea	2011a;	Weber	2013).	The	approach	to	information	described	above allows	a	quantitiative	assessment	of	this	claim	and	reveals	that	it	is	more	plausible as	a	claim	about	the	sources	of	specificity	for	evolutionary	change	than	as	a	claim about	the	sources	of	developmental	specificity	(Griffiths	et	al.	2015c,	543-550).	But the	idea	that	nucleic	acids	are	uniquely	'informational	molecules'	is	already vindicated	by	the	fact	that	they	were	the	key	innovation	that	made	massive,	reliable information	transfer	between	cells	practical,	and	is	simply	not	threatened	by	the parity	principle. In	conclusion,	all	three	heredity	systems	have	evolutionary	significance.	The	genetic heredity	system	may	well	have	been	optimized	for	the	ability	of	organisms	to transfer	biological	specificity	between	cells.	This	ability,	perhaps	the	key	innovation in	the	history	of	life,	was	dependent	on	the	invention	of	nucleic-acid	based	heredity. However,	the	addition	of	epigenetic	and	exogenetic	heredity	systems	amplifies	that information,	allowing	a	greater	range	of	products	to	be	specified	by	the	same template	resources.	Epigenetic	mechanisms	also	provide	the	control	engineering that	enables	the	flexible	expression	of	those	template	resources	during	development, and	in	response	to	different	environmental	demands.	At	least	some	epiand exogenetic	mechanisms	of	inheritance	have	been	optimized	to	allow	organisms	to respond	to	environmental	demands	on	timescales	intermediate	between	individual development	and	genetic	selection.	In	modern	organisms	the	amount	of	information transmitted	between	the	generations	through	epiand	exo-genetic	heredity	may exceed	the	amount	transmitted	in	the	underlying	nucleic	acid	template	resources considered	in	isolation,	although	nothing	important	turns	on	which	form	of	heredity 'wins'	in	this	comparison,	as	each	clearly	plays	a	significant	role. 7.	Proximate	and	ultimate	information Our	concern	in	the	previous	sections	has	been	with	proximate	information, information	that	does	causal	work	in	living	systems.	In	this	section	we	turn	to ultimate	information,	to	information	defined	in	terms	of	evolutionary	purposes	and its	relationship	to	proximate	information. Teleosemantic	accounts	define	the	information	in	a	biological	object	in	terms	of	the effect	that	that	object	was	designed	to	produce	by	natural	selection.	This	is	'ultimate information'	because	it	is	derived	from	ultimate	biology	–	the	study	of	why organisms	evolved	to	their	current	state.	The	simplest	teleosemantic	theory	would treat	a	gene	or	an	environmental	factor	as	an	instruction	to	produce	whatever fitness-enhancing	effect(s)	that	genetic	or	environmental	factor	produced	in	earlier generations.	Naturally,	the	teleosemantic	theories	found	in	the	current	literature	are subtler	than	this.	The	most	thoroughly	developed	is	Nicholas	Shea's	theory	of 'inherited	information'	(Shea	2011b). Shea	accepts	the	parity	thesis,	and	argues	that	inherited	information	is	found	in	all genetic	causes	of	development	and	in	certain	special	environmental	causes	of development.	We	agree	with	Shea	that	both	genetic	and	environmental	causes	in development	can	carry	inherited	information,	and	that	this	fact	can	be	used	to	show that	these	causes	sometimes	play	the	same	role	in	evolution.	Our	concern	is	that	the presence	of	inherited	information,	whether	in	genes	or	environment,	cannot contribute	to	proximate	explanations	of	biological	development.	If	two	organisms contain	the	same	allele,	one	by	inheritance	and	the	other	as	a	de	novo	mutation,	then according	to	Shea	the	first	allele	contains	inherited	information	and	the	second	does not.	But	they	will,	of	course,	affect	the	organism	that	carries	them	in	exactly	the same	way.	The	presence	or	absence	of	'inherited	information'	in	Shea's	sense	makes no	difference	in	development	(Griffiths	2013	and	see	above).	This	highlights	the urgency	to	identify	the	link	between	ultimate	and	proximate	information. Finding	the	link	is	made	easier	by	the	fact	that	Shea's	formulation,	unusually amongst	teleosemantic	theories,	makes	a	connection	with	the	Shannon	formalism. According	to	Griffiths	(2016)	the	essence	of	Shea's	proposal	is	that	a	developmental cause	contains	inherited	information	if	(a)	manipulating	that	cause	affects	how	the organism	develops,	(b)	the	causal	variable	contains	mutual	information	about	the environment,	and	(c)	the	whole	system	evolved	because	it	was	fitness	enhancing	by matching	appropriate	developmental	outcomes	to	different	environments.7	We	can apply	this	proposal	to	a	typical	case	of	adaptive	phenotypic	plasticity,	such	as	the development	of	defensive	amour	in	water	fleas	when	developing	fleas	are	exposed to	chemical	traces	of	predators	(Lüning	1992).	The	mechanism	that	produces	this effect	contains	inherited	information	about	the	need	for	amour. Griffiths	goes	on	to point	out	that	we	can	remove	the	claims	about	history	from	Shea's	definition	of information	to	get	a	corresponding	proximal	notion	of	information,	which	Griffiths terms	'adaptive	information'.	A	developmental	cause	contains	adaptive	information if	it	contains	mutual	information	about	an	environmental	variable	and	affects 7	Presenting	the	proposal	in	Shea's	own	terms	would	require	a	lengthy	explanation of	several	proprietary	notions.	In	his	terminology	a	cause	contains	inherited information	if: a)	there	is	a	consumer	system	which	is	caused	by	a	range	of	tokens,	including tokens	of	type	R,	to	produce	a	range	of	outputs,	with	a	specific	evolutionary function	for	each	type	of	output,	and	where	every	token	satisfies	(b)	to	(d) with	respect	to	some	content; (b)	Rs	carry	the	correlational	information	that	condition	C	obtains; (c)	an	evolutionary	explanation	of	the	current	existence	of	the	representing system	adverts	to	Rs	having	carried	the	correlational	information	that condition	C	obtains;	and (d)	C	is	the	evolutionary	success	condition,	specific	to	Rs,	of	the	output	of	the consumer	system	prompted	by	Rs.	(Shea	2013,	5) development	so	that	developmental	outcomes	and	environments	correlate	in	a	way that	enhances	fitness.	The	relationship	between	'adaptive	information'	and 'inherited	information'	is	exactly	the	same	as	the	relationship	between	an	adaptive trait	and	a	trait	that	is	an	adaptation.	Every	adaptation	was,	by	definition,	an adaptive	trait	in	the	past,	and	an	adaptive	trait	will	become	an	adaptation	in	future generations	if	it	is	successful	enough.	The	ideas	of	adaptiveness	and	adaptation	are complementary	and	both	are	needed	to	describe	the	process	of	natural	selection.	In the	same	way,	both	adaptive	information	and	inherited	information	are	needed	to describe	the	natural	selection	of	information	systems. It	is	now	possible	to	state	the	relationship	between	ultimate	and	proximate information.	Adaptive	information	is	simply	proximate	biological	information,	in	the sense	defined	in	earlier	sections,	when	the	presence	of	that	information	enhances the	fitness	of	the	organism.	Ultimate	information	–	or	'inherited	information'	is proximate	biological	information	that	exists	in	current	organisms	because	earlier instances	of	the	same	information	led	to	the	evolutionary	success	of	ancestral organisms.	Evolutionary	theory	leads	us	to	expect	that	much	of	the	proximate biological	information	we	can	measure	in	living	organisms	is	also	inherited information.	The	presence	of	DNA	sequences	that	contain	Crick	information	about the	structure	of	biomolecules	is	explained	by	the	adaptive	advantages	of	having been	able	to	produce	those	molecules	in	the	past	(pseudogenes	that	can	no	longer be	transcribed	might	be	said	to	carry	'vestigial	Crick	information').	The	presence	of proximate	information	in	epigenetic	marks	and	exogenetically	inherited	factors	is explained	by	the	adaptive	advantages	of	being	able	to	regulate	genome	expression in	the	past,	and	of	the	ability	to	adaptively	match	the	environment	on	shorter timescales,	as	explained	above. Teleosemantic	accounts	of	biological	information	are	an	essential	complement	to theories	of	proximate	information	of	the	kind	we	have	presented	above. Teleosemantic	information	should	feature	in	ultimate	explanations	of	the	proximate biological	information	that	we	can	measure	in	living	organisms.	The	mistake	in much	of	the	existing	literature	is	to	try	to	use	teleosemantics	to	define	the	proximate information	that	is	a	substantive	causal	factor	in	the	operation	of	living	systems. Proximate	information	can	–	indeed	it	must	–	exist	before	inherited	information	in order	to	be	selected	and	thereby	get	to	count	as	inherited	information.	Furthermore, not	all	the	proximate	information	we	can	measure	in	living	organisms	is	also ultimate	information,	just	as	not	every	feature	of	an	organism	is	an	adaptation,	but we	can	expect	that	much	if	will	be. 8.	Conclusion In	1958	Francis	Crick	introduced	the	idea	that	biological	specificity	could	take	the form	of	information	coded	in	the	order	of	bases	in	amino	acids.	Here	and	elsewhere we	have	argued	that	the	idea	of	biological	information	is	best	understood	in	a	way inspired	by	his	work	(Griffiths	and	Stotz	2013). Crick's	definition	of	information	as	the	precise	determination	of	the	order	of elements	in	a	biomolecule	can	be	analysed	using	the	Shannon	formalism	and	the interventionist	approach	to	causation.	The	presence	of	information	in	Crick's	sense corresponds	to	a	highly	specific	causal	relationship	between	the	order	of	elements in	a	biomolecule	and	some	cause	of	that	biomolecule,	such	as	the	nucleic	acid	from which	it	was	transcribed	or	translated.	Specificity	can	be	measured	as	the	mutual information	between	interventions	on	the	cause	variable	and	the	effect	variable	(the order	of	elements	in	the	downstream	biomolecule). This	definition	of	information	can	be	generalized.	First,	other	causes	of	the	structure of	biomolecules	can	also	be	highly	specific,	and	thus	contain	Crick	information. Second,	we	can	apply	the	same	measures	to	other	causal	relationships	within organisms,	where	the	effect	variable	is	not	simply	the	order	of	elements	in	a biomolecule.	For	example,	enzymes	are	highly	specific	for	their	substrates,	and	this relationship	can	be	measured	in	the	same	way	that	we	measure	the	specificity	of	a gene	for	its	product.	Biological	information,	we	propose,	is	the	very	same	thing	as biological	specificity.	Living	systems	are	'informed	systems'	because	they	exercise	a high	degree	of	specificity	over	their	internal	processes.	Crick	information	is	a	special case	of	biological	information,	just	as	the	specificity	of	nucleic	acids	for	their products	is	a	special	case	of	biological	specificity. Both	Crick	information	and	biological	information	more	broadly	can	be	inherited	via genetic,	epigenetic	and	exogenetic	mechanisms.	But	there	is	an	important	sense	in which	the	genetic	heredity	systems	stands	out	from	the	others:	nucleic	acid	heredity was	the	key	innovation	in	evolution	that	allowed	the	highly	efficient	transfer	of	large quantities	of	Crick	information	from	one	cell	to	the	next.	Many	other	heredity systems	exploit	this	system	to	achieve	the	transfer	of	specificity	to	the	next	cell	or organism	generation.	But	the	special	status	of	genetic	heredity	in	this	respect	does not	support	some	of	the	other	claims	about	it	in	the	philosophical	literature.	For example,	it	does	not	support	the	widely	held	view	that	genes	contribute	much	more information	to	development	that	other	factors.	In	modern	organisms	a	small number	of	coding	sequences	produces	orders	of	magnitude	more	transcripts through	epigenetic	regulation	of	gene	expression,	and	does	so	in	a	highly	regulated manner	across	space	and	time.	When	we	look	for	the	source	of	the	specificity manifested	in	this	regulated	genome	expression	much	of	it	will	be	found	in epigenetic	and	exogenetic	sources.	This	is	not	to	say	that	all	three	heredity	systems play	the	same	role	in	development,	but	the	differences	between	them	are	not captured	by	saying	that	one	contains	all	or	most	of	the	information	expressed	in development. Nor	is	it	the	case	that	only	genetic	information	is	inherited.	Epigenetic	and exogenetic	heredity	also	transmit	information	across	generations.	Because	of	this, all	three	forms	of	heredity	have	evolutionary	significance:	they	all	affect	which phenotypes	will	be	seen	in	the	next	generation	as	the	result	of	the	differential success	of	competing	phenotypes	in	the	previous	generation.	Therefore	they	all affect	the	dynamics	of	evolution,	as	can	be	seen	in	quantitative	genetic	models	that incorporate	these	other	forms	of	heredity.	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