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EVIDENCE FOR EVOLUTION FROM THE GENES FUNCTIONING IN SIGNALING MECHANISMS

HOMOLOGIES ARE PREDICTED BY THE EVOLUTIONARY MODEL

Signal molecules and their receptors do not have to form a specific shape as long as they can recognize each other.  For example, a specific signal could be relayed between body cells with a signal molecule with the following shape, as long as the appropriate receptors recognized it.

MOLECULE
Of course, the same signal could be relayed between body cells by a signal molecule with an entirely different structure, as long as there were receptors to recognize it (such as the following shape for example).
MOLECULE

When comparing signaling molecules within one organism or between organisms, there is no pattern which would be expected if evolution had not occurred.  Analysis of the signaling molecules used in a single organism and those of different organisms identifies homologous groups of genes predicted in the evolutionary model. 

1) HOMOLOGIES IN GENE FAMILIES

     Since a signal molecule could possess any shape/sequence as long as receptors existed which recognized the signal’s shape, there is no reason to expect that there should be gene families of signal molecules and their receptors.  Neuropeptide Y does not have to have any similarity to any other signal in order to function, nor does fibroblast growth factor 9 nor does insulin nor does oxytocin.  Each signal could be unique.  Signals are not entirely unique—most belong to gene families which seem to have been derived from ancestral genes which duplicated and were subsequently modified. 

     For example, the signals of the FGF gene family promote a growth in a variety of distinct tissues such as the development of the endocrine pancreas (FGF2), teeth (FGF4), skin (FGF7), and limbs (FGF8 and 10).  They all seem to be modified duplications of an ancestral gene.  The insulin gene family includes insulin (which lowers blood sugar levels), relaxin (which allows more movement between the pubic bones during childbirth), and somatomedins (whose diverse roles include that of IGF3 in promoting the descent of the testes).  While most members of the NPY gene family regulate body lipid levels, NPY also affects the predisposition to alcoholism and seminalplasmin is a protein in semen which regulates calcium transport and is involved in the changes to the acrosome at fertilization.  Growth hormone (which promotes growth) and prolactin (which has many diverse roles in vertebrates but which is best known for its promotion of milk production in mammals) are members of the same gene family.  The calictonin gene family includes hormones which affect blood calcium levels and blood pressure.  The differentiation of many diverse body tissues is promoted by the diverse members of several gene families such as the TGFβ family, WNT family, SHH family, etc.

     Not only has genetic analysis demonstrated that the existence of gene families of signal molecules composed of modified duplications of ancestral genes, the analysis indicates when in vertebrate history the duplications which produced separate family members occurred.  A great deal of evidence already indicates that two rounds of genome duplication occurred prior to the evolution of jawed vertebrates.  Many ancestral signal molecules seem to have been duplicated arisen in these events. 

 

2) HOMOLOGIES IN DISTANTLY RELATED ORGANISMS

     Given that signal molecules and their receptors could take any form, there is absolutely no reason to predict that homologous signals would exist in distantly related organisms.  For example, if fruit flies and humans are completely unrelated to each other and at no time did they share a common ancestor, there is no reason to suppose that the signals which guide the development of a ball of cells into a fly larva would be similar to those which guide the development of a different ball of cells into a human infant.  There is no reason to predict that the neuropeptides used in one species would be the same as those from another species if these species did not share a common ancestry.  There is no reason to think that the hormones (such as prolactin) which promote milk production in mammals would exist in vertebrates which do not produce milk.  There is no reason to predict that organisms as diverse as fruit flies and humans would share many of the same signaling molecules.

 

C) THE GENE CLADOGRAM AND “IRREDUCIBLE COMPLEXITY”

     One of the main arguments in “Intelligent Design” is that of “irreducible complexity.”  Advocates of Intelligent Design have argued that molecular systems in living organisms involve multiple interacting genes and that such complex pathways could not have evolved gradually.  Analysis of the distribution of signaling genes strongly refutes this.  As the following gene cladogram illustrates, the components of molecular pathways do not appear all at once in complex pathways.  Instead, it is apparent that throughout evolution organisms incorporated signal molecules which their ancestors possessed into new roles which were elaborated over time.  The complex molecular systems found in humans are not irreducibly complex in that, while their multiple interacting parts may be required for human life, no such system is a requirement for life in general.  Early cells and early animals did not require the complex developmental signals, immune signals, reproductive signals, nervous system signals, etc. found in humans.  A much simpler set of molecular mechanisms were sufficient for these earlier organisms.  Some of these organisms evolved new signaling pathways and new molecular systems through the duplication and modification of existing genes, the shuffling of protein domains, mutation, etc.  At first these novelties would not have been essential for life, but rather supplementary systems which gave their bearers an advantage over other organisms.  The descendants of these organisms evolved in ways so that these molecular mechanisms were required to support greater molecular complexity.

     The following list contains a sampling of examples in which the signaling molecules which humans use in complex pathways actually evolved long before these complex pathways existed.  opiates evolved long before there were animals which would utilize them to lessen the sensation of pain and cortisol evolved long before animals evolved which would utilize it to mediate responses to stress.  Testosterone and estrogen also predate both animals and the animal use of these hormones to regulate gamete production, the maturation of reproductive organs, or the regulation of reproductive drives and behaviors through the limbic systems of vertebrate brains.  Interleukin and cytokines evolved in primitive animals, long before higher vertebrates would require it for the complex interaction between white blood cells.  Oxytocin evolved before bilateran animals, long before mammals would use it to induce orgasm, uterine contractions at childbirth, or the ejection of milk during lactation.  The embryonic growth factors which promote the development of human brains, bones, limbs, digestive organs, etc. are homologous to growth factors which existed in invertebrates long before the evolution of vertebrate brains, limbs, bones, etc. Prolactin evolved in fish long before mammals would use it to stimulate the production of milk.

 

THE GENE CLADOGRAM

Many of the genes which humans require to be human evolved long before humans.  The distribution of these genes among modern organisms supports that modern groups of organisms can be organized into clades which share a common ancestry.  The same clades of organisms which are supported through the analysis of signaling molecules are supported by the analysis of other genes, anatomical features, embryological development, and the fossil record.  The organization of modern organism into a nested hierarchy of clades is predicted by the evolutionary model but not alternative models.

 

ALL LIFE

--steroids are universally found in organisms, and function as components of the cell membrane, hormones, vitamins, and cytotoxins.  Some bacteria convert cholesterol into hormones (Agarwal, 1993; Milanesi, 2004).  

--E. coli synthesize a protein similar to insulin (LeRoith, 1981).

--The opioid met-enkalphin promotes cell proliferation in several bacteria which possess opioid receptors (Zagon, 1992; Danielson, 1999).

 

EUKARYOTES

--Some algae, plants, and plants have been shown to convert cholesterol into hormones such as cortisol, mineralcorticoids, progestins, testosterone, estrogens (and estrogen receptors), and ecdysone (Agarwal, 1993; Milanesi, 2004). 

--Several protozoans are known to make peptides similar to adrenocorticotropic hormone, β-endorphin, and dynorphin (LeRoith, 1981).

 

METAZOANS

--Starfish possess molecules similar to interleukin-1 (Hine, 1990).  

--Cnidarians possess FMRFamide-like peptide, oxytocin/vasopressin, and other peptides (Thorndyke, )..

--Most metazoan animals use sex steroids in differentiation of male and female reproductive structures and oxytocin for the majority of the acute events that occur at these structures structures (Ivell, 1999) 

--Cnidarians and bilaterans share a number of developmental genes such as forkhead, emx, aristaless, goosecoid, brachury, wnt, and nanos (Galliot, 2000).

 

BILATERANS

--Oxytocin-like peptides are known in invertebrates.  In worms, annetocin functions in egg-laying and the contraction of neprhidia (which propel both wastes and gametes) (Ivell, 1999)

--Worms and tunicates possess interleukin-1 and TNF; hornworms produce interleukin-1 and interleukin-6.  Three kinds of cytokines are known from invertebrates (Hine, 1990).

 

COELOMATE

--Evidence indicates that mollusks synthesize a number of peptide hormones such as vasopressin, vasotocin, oxytocin, CRF, ACTH, αMSH, enkephalin, dynorphin, somatostatin, substance P, glucagons, insulin, secretin, gastrin, calcitonin, VIP, GIP, PP, FMRRamide, AKH, dopamine, serotonin, histamine, and octopamine (Thorndyke, ).  --Insects synthesize oxytocin, vasotocin, vasopressin, neurophysin, substance P, bombesin, gastrin/CCK, VIP, PP, serotonin, and dopamine (Thorndyke, ). 

--Annelid worms synthesize dynorphin, and enkelpalin-like substances. 

--A number of peptides similar to oxytocin/vasotocin are known in invertebrates such as Arg-conopressin-S in mollusks, Lys-conopressin-G in mollusks, cephalotocin in mollusks, annetocin in annelids, Lom-DH in arthropods, and Stp-OLP in tunicates.  Mollusk conopressin genes are homologous to those of vasoticn/oxytocin in vertebrtates (Hoyle, 1998).

--Homologs of neuropeptide Y are known from invertebrates such as worms and mollusks (Hoyle, 1998).

--Opioid-like peptides known from arthropods, mollusks, annelids, protists, and even prokaryotes (Danielson, 1999).

--Wnt proteins had undergone duplication to produce a multigene family before the split of coelomate lineages.  Wnt1 through Wnt7 originated before this split. (Sidow, 1992).   

--During development, the engrailed gene expressed in posterior segments and hairy (Drosophila)/her1 (zebrafish) involved in segmentation (Robertis, 1997)

 

DEUTEROSTOMES

--Protochordates synthesize bombesin, calcitonin, β endorphin, enkephalin, gastrin/CCK, glucagons, insulin, LHRH, motilin, αMSH, neurotensin, PP, prolactin, secretin, somatostatin, substance P, VIP, serotonin (Thorndyke, ).

--The protochordate Ciona has a single peptide of this gene family from which CCK and gastrin are thought to have evolved. (Johnsen, 1997; Johnsen, 1996; Hoyle, 1998). 

--Tunicates use Wnt and Frizzled (the receptor for Wnt) signaling in development, and Wnt5 functions in the development of the notochord (Hotta, 2003). 

--Tunicate larvae express a BMP protein during embryological development in a pattern similar to vertebrates (Miya, 1996).

 

UROCHORDATES

--Thyroid hormone regulates the metamorphosis of both fish and amphibians (Marchand, 2004).  Almost all vertebrates secrete thyroid hormones.  Thus, one of the major regulators of endothermic metabolism is present in ectotherms as well.   It is required for metamorphosis in tunicates, fish , and amphibans  (Tata, 2000; Jones, 2002; Carosa, 1998). 

--Tunicates possess genes for all major peptide hormone receptors (such as insulin and gonadotropins), except growth hormone (Dehal, 2002).   

--Protochordates synthesize bombesin, calcitonin, β endorphin, enkephalin, gastrin/CCK, glucagons, insulin, LHRH, motilin, αMSH, neurotensin, PP, prolactin, secretin, somatostatin, substance P, VIP, serotonin (Thorndyke, )..

--A number of peptides similar to oxytocin/vasotocin are known in invertebrates such as Arg-conopressin-S in mollusks, Lys-conopressin-G in mollusks, cephalotocin in mollusks, annetocin in annelids, Lom-DH in arthropods, and Stp-OLP in tunicates.  Mollusk conopressin genes are homologous to those of vasoticn/oxytocin in vertebrtates (Hoyle, 1998).

--The tunicate neuropeptide cionin seems to be related to vertebrate peptides, like CCK  (Hoyle, 1998).

--The protochordate Ciona has a single peptide of this gene family from which CCK and gastrin are thought to have evolved. (Johnsen, 1997; Johnsen, 1996).  

--Tunicates use Wnt and Frizzled (the receptor for Wnt) signaling in development, and Wnt5 functions in the development of the notochord (Hotta, 2003). 

--Tunicate larvae express a BMP protein during embryological development in a pattern similar to vertebrates (Miya, 1996).

 

CRANIATES

--GH is the only member of the gene family known to exist in agnathans. (Sower, 2001). 

--Enkalphin and POMC are known in several non-amniotes, including aganthans.  The duplication of the ancestral gene preceded craniates (Danielson, 1999).  . 

 

VERTEBRATES

--A duplication of the ancestral gene occurred before lampreys to produce NPY and PYY(Larhammar, 1993).  . 

--All vertebrates possess neuropeptide Y in central and peripheral nervous systems (Larhammar, 1993).

--Much of the expansion of the expansion of the interleukin family has occurred recently in separate events in early vertebrates (Huising, 2004).

--Early in vertebrate evolution, additional duplications WNT occurred (Sidow, 1992). 

--There are three GnRH genes known which appear to have resulted from an ancestral gene which was duplicated in ancestral vertebrates.  Two of the three resulting decapeptides have the same amino acid sequence in all known species (Fernald, 1999).

 

GNATHOSTOMES

--Substance P is related to kinins known in amphibians and sharks (Hoyle, 1998).

--Only three amino acids are variant between shark and human NPY; it is one of the most highly conserved peptides in vertebrates (Herzog, 1995).

--Proorphanin seems to have resulted from an early duplication of the gene for proenkalphin in gnathostomes. (Danielson, 1999). 

--Since cartilaginous fish and higher vertebrates possess both CCK and gastrin, the divergence of these homologous genes occurred before the origin of cartilaginous fish (Johnsen, 1997; Johnsen, 1996).  

--Galanin is expressed in the hypothalamus where it stimualates LH secretion.  It also affects the gastrointestinal tract.  In humans, mutations can affect stature, overall development, obesity, and the development of the reproductive system.  It is neuropeptide known from gnathostome vertebrates (OMIM).

--PTHrP known from brain of cartilaginous fish (Ingleton, 1996).

 

BONY FISH AND TETRAPODS

--Prolactin and growth hormone are known in mammals and bony fish (Sower, 2001).

--The N-acetylation of a-MSH and b-endorphin occurs before they are secreted in bony fish and mammals (Dores, 1994).  

--Basal actinopterygians, lungfish, amphibians, marsupials, and primitive placental mammals possess two GnRH genes (Fernald, 1999; King, 1995).

--The response of the cells of the bowfin aorta to bradykinin is comparable to those of mammals.  There is only one amino acid difference between the forms of bradykinin in humans and bowfins (Conlon, 1995).

--Interferons are definitely known from amniotes and possible homologs have also been identified in fish (Magor, 2001). 

 

SARCOPTERYGIANS

--The distribution of neuropeptide Y, a-MSH, and ANF recognition sites in the brains of lungfish is similar to that observed in amphibians.  The distribution of FMRF-amide in lungfish brains is more similar to amphibians than other fish (Vallarino, 1998). 

--Another duplication of the proenkalphin gene produced prodynorphin in the lineage which produced sarcopterygians and tetrapods (Danielson, 1999). 

--The lungfish POMC gene possesses a g-MSH sequence like the gene in tetrapods and unlike the gene in other fish (Lee, 1999).  The distribution of a-MSH recognition sites in the brains of lungfish is similar to that observed in amphibians (Vallarino, 1998).   

 

TETRAPODS

--Neurokinin A is known in all tetrapods. (Hoyle, 1998). 

--A duplication produced PP in tetrapods and some teleosts possess PY (Larhammar, 1993). 

 

AMNIOTES

--Interleukin 2 and 15 use the same β and γ chains but differ in their α chains.  They are only known in amniotes.  IL2 stimulates T cell production.  IL18 is only known in amniotes (Kaiser, 2004).

 

MAMMALS

--Interleukin-6 is only known from mammals (Magor, 2001). 

--The mutation in ancestral vasotocin which gave rise to vasopressin seems to have occurred only in the ancestral mammals; all non-mammalian vertebrates possess vasotocin (Hoyle, 1998).

--Tachykinin genes are known in mammals. (Hoyle, 1998).

--Expansion of the interleukin family occurred in ancestral mammals (Huising, 2004).

 

PRIMATES

--While there is only a single growth hormone gene in most vertebrates, gene duplications have produced multiple copies in teleost fish, goats, and primates (the latter of which have four genes) (Chuzhanova, 2000).

--The IFNα family seems to have arisen from after the primate lineage arose (Gillespie, 1983).

 

CATARRHINE PRIMATES

The 5HTT gene is regulated by an upstream polymorphic repetitive element (Reif, 2003).