Riddles in code; is there a gene for language?

07/09/2014 |

‘I have…’

Words are like genes; on their own they are not very powerful.  But apply them with others in the right phrase, at the right time and with the right emphasis, and they can change everything.

‘I have a dream…’

Genes are coded information.  They are like the words of a language, and can be combined into a story which tells us who we are.

The stories we choose to tell are powerful; they can change who we become, and also change the people with whom we share them.

‘I have a dream today!’

Language is a means for coding and passing on information, but it is cultural, and definitely non-genetic.  Nevertheless, for our speech capacity to have evolved, our ancestors must have had a body equipped to make speech sounds, along with the mental capacity to generate and process this language ‘behaviour’.  Our body’s development is orchestrated through the actions of relevant genes.  If the physical aspects of language ultimately have a genetic basis, this implies that speech must derive, at least in part, from the actions of our genes.

The hunt for genes involved with language led researchers at the University of Oxford to investigate an extended family (known as family KE).  Some family members had problems with their speech.  The pattern of their symptoms suggested that they inherited these difficulties as a ‘dominant’ character, and through a single gene locus.

The FoxP2 gene encodes for the ‘Forkhead-Box Protein-2’; a transcription factor. This is a type of protein that interacts with DNA (shown here as a pair of brown spiral ladders), and influences which genes are turned on in the cell, and which remain silent. This diagram shows two Forkhead box proteins, which associate with each other when active. This bends the DNA strand and makes critical areas of the genetic code more accessible (Image: Wikimedia Commons)

The FOXP2 gene encodes for the ‘Forkhead-Box Protein-2’; a transcription factor. This is a type of protein that interacts with DNA (shown here as a pair of brown spiral ladders), and influences which genes are turne... mored on in the cell, and which remain silent. This diagram shows two Forkhead box proteins, which associate with each other when active. This bends the DNA strand and makes critical areas of the genetic code more accessible (Image: Wikimedia Commons)

Discovery of another unrelated patient with the same symptoms confirmed that the condition was linked to a gene known as FOXP2  (short for ‘Forkhead Box Protein-2’).  This locus encodes a ‘transcription factor’; a protein that influences the activation of many other genes.  FOXP2 was subsequently dubbed ‘the gene for language’.  Is that correct?

Not really.  FOXP2 affects a range of processes, not just speech.  The mutation which inactivates the gene causes difficulties in controlling muscles of the face and tongue, problems with compiling words into sentences, and a reduced understanding of language.  Neuroimaging studies showed that these patients have reduced nerve activity in the basal ganglia  region of the brain.  Their symptoms are similar to some of the problems seen in patients with debilitating diseases such as Parkinson’s and Broca’s Aphasia; these conditions also show impairment of the basal ganglia.

Genes code for proteins by using a 3-letter alphabet of adenine, thymine, guanine and cytosine (abbreviated to A, T, G and C). These nucletodes are knwn as ‘bases’ (are alkaline in solution) and make matched pairs which form the ‘rungs of the ladder’ of the DNA helix. Substituting one base for another (as happens in many mutations) can change the amino acid sequence of the protein a gene encodes. Changes may make no impact on survival, allowing the DNA sequence to alter over time. Changes that affect critical sections of the protein (e.g. an enzyme’s active site), or critical proteins like FoxP2, are rare (Image: Wikimedia Commons)

Genes code for proteins by using a 3-letter alphabet of adenine, thymine, guanine and cytosine (abbreviated to A, T, G and C). These nucletodes are knwn as ‘bases’ (are alkaline in solution) and make matched pairs w... morehich form the ‘rungs of the ladder’ of the DNA helix. Substituting one base for another (as happens in many mutations) can change the amino acid sequence of the protein a gene encodes. Changes may make no impact on survival, allowing the DNA sequence to alter over time. Changes that affect critical sections of the protein (e.g. an enzyme’s active site), or critical proteins like FOXP2, are rare (Image: Wikimedia Commons)

Genes provide the code to build proteins.  Proteins are assembled from this coding template (the famous triplets) as a sequence of amino acids, strung together initially like the carriages of a train and then folded into their finished form.  The amino acid sequences of the FOXP2 protein show very few differences across all vertebrate groups.  This strong conservation of sequence suggests that this protein fulfils critical roles for these organisms.  In mice, chimpanzees and birds, FOXP2 has been shown to be required for the healthy development of the brain and lungs.  Reduced levels of the protein affect motor skills learning in mice and vocal imitation in song birds.

The human and chimpanzee forms of FOXP2 protein differ by only two amino acids. We also share one of these changes with bats.  Not only that, but there is only one amino acid difference between FOXP2 from chimpanzees and mice.  These differences might look trivial but they are probably significant.  FOXP2 has evolved faster in bats than any other mammal, hinting at a possible role for this protein in echolocation.

Mouse brain slice, showing neurons from the somatosensory cortex (20X magnification) producing green fluorescent protein (GFP). Projections (dendrites) extend upwards towards the pial surface from the teardrop-shaped cell bodies. Humanised Foxp2 in mice causes longer dendrites to form on specific brain nerve cells, lengthens the recovery time needed by some neurons after firing, and increases the readiness of these neurons to make new connections with other nerves (synaptic plasticity). The degree of synaptic plasticity indicates how efficiently neurons code and process information (Image: Wikimedia Commons)

Mouse brain slice, showing neurons from the somatosensory cortex (20X magnification) producing green fluorescent protein (GFP). Projections (dendrites) extend upwards towards the pial surface from the teardrop-shaped ce... morell bodies. Humanised Foxp2 in mice causes longer dendrites to form on specific brain nerve cells, lengthens the recovery time needed by some neurons after firing, and increases the readiness of these neurons to make new connections with other nerves (synaptic plasticity). The degree of synaptic plasticity indicates how efficiently neurons code and process information (Image: Wikimedia Commons)

Changing the form of mouse FOXP2 to include these two human-associated amino acids alters the pitch of these animals’ ultrasonic calls, and affects their degree of inquisitive behaviour.  Differences also appear in their neural anatomy.  Altering the number of working copies (the genetic ‘dose’) of FOXP2 in mice and birds affects the development of their basal ganglia.

Mice with ‘humanised’ FOXP2 protein show changes in their cortico-basal ganglia circuits along with altered exploratory behaviour and reduced levels of dopamine (a neurotransmitter  that affects our emotional responses).  So too, human patients with damage to the basal ganglia show reduced levels of initiative and motivation for tasks.

This suggests that FOXP2 is part of a general mechanism that affects our thinking, particularly around our initiative and mental flexibility.  These are critical components of human creativity, and are as it happens, essential for our speech.

Basal ganglia circuits process and organise signals from other parts of the brain into sequences.  Speaking involves coordinating a complex sequence of muscle actions in the mouth and throat, and synchronising these with the out-breath.  We use these same muscles and anatomical structures to breathe, chew and swallow;  our ability to coordinate them affects our speech, although this is not their primary role.

Family KE’s condition, caused by a dominant mutation in the FoxP2 gene, follows an autosomal (not sex-linked) pattern of inheritance, as shown here. Dominant mutations are visible when only one gene copy is present. In contrast a recessive trait is not seen in the organism unless both chromosomes of the pair carry the mutant form of the gene. The FoxP2 transcription factor protein is required in precise amounts for normal function of the brain. The loss of one working FoxP2 gene copy reduces this ‘dose’ which is enough to cause the problems that emerged as family KE’s symptoms (Image: Annotated from Wikimedia Commons)

Family KE’s condition, caused by a dominant mutation in the FOXP2 gene, follows an autosomal (not sex-linked) pattern of inheritance, as shown here.Dominant mutations are visible when only one gene copy is present. In... more contrast a recessive trait is not seen in the organism unless both chromosomes of the pair carry the mutant form of the gene. The FOXP2 transcription factor protein is required in precise amounts for normal function of the brain. The loss of one working FOXP2 gene copy reduces this ‘dose’ which is enough to cause the problems that emerged as family KE’s symptoms (Image: Annotated from Wikimedia Commons)

In practice, very few of our 25,000 genes are individually responsible for noticeable characteristics.  Most genetically inherited diseases result from the effects of multiple gene loci.  FOXP2 is unusual because of its ‘dominant’ genetic character.  It does not give us our language abilities, but it is involved in the neural basis of our mental flexibility and agility at controlling the muscles of our mouths, throats and fingers.

In addition, genes are only part of the story of our development.  The way we think and subsequently behave alters our emotional state.  Feeling stressed or calm affects which circuits are active in our brain.  This alters the biochemical state of body organs and tissues, particularly of the immune system, modifying which genes they are using.

The dance between the code stored in our genes and the consequences of our thoughts builds us into what we are mentally, physically and socially.  This story is ours to tell.  By our experience, and with this genetic vocabulary, we create what we become.

Text copyright © 2015 Mags Leighton. All rights reserved.

References
Chial H (2008)  ‘Rare genetic disorders: Learning about genetic disease through gene mapping, SNPs, and microarray data’ Nature Education 1(1):192  http://www.nature.com/scitable/topicpage/rare-genetic-disorders-learning-about-genetic-disease-979
Clovis YM et al. (2012) ‘Convergent repression of Foxp2 3′UTR by miR-9 and miR-132 in embryonic mouse neocortex: implications for radial migration of neurons’  Development 139, 3332-3342.
Enard, W (2011) ‘FOXP2 and the role of cortico-basal ganglia circuits in speech and language evolution’  Current Opinion in Neurobiology  21; 415–424
Enard, W et al (2009)  A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice  Cell 137 (5); 961–971  http://www.sciencedirect.com/science/article/pii/S009286740900378X
Feuk L et at., Absence of a Paternally Inherited FOXP2 Gene in Developmental Verbal Dyspraxia, in The American Journal of Human Genetics, Vol. 79 November 2006, p.965-72.
Fisher SE and Scharff C (2009) ‘FOXP2 as a molecular window into speech and language’  Trends in Genetics 25 (4); 166-177
Lieberman P  (2009)  ‘FOXP2 and Human Cognition’  Cell 137; 800-803
Marcus GF & Fisher SE (2003) ‘FOXp2 in focus; what can genes tell us about speech and language?’  Trends in Cognitive Sciences 7(6); 257-262
Reimers-Kipping S et al. (2011) ‘Humanised Foxp2 specifically affects cortico-basal ganglia circuits’ Neuroscience 175; 75-84
Scharff C & Haesler S (2005) ‘An evolutionary perspective on Foxp2; strictly for the birds?’ Current opinion in Neurobiology 15:694-703
Vargha-Khadem F et al. (2005) ‘FOXP2 and the neuroanatomy of speech and language’  Nature Reviews Neuroscience 6, 131-138 http://www.nature.com/nrn/journal/v6/n2/full/nrn1605.html
Wapshott N (2013)  ‘Martin Luther King's 'I Have A Dream' Speech Changed The World’ Huffington post, 28th August 2013  http://www.huffingtonpost.com/2013/08/28/i-have-a-dream-speech-world_n_3830409.html
Webb DM & Zhang J (2005) ‘Foxp2 in song learning birds and vocal learning mammals’  Journal of Heredity 96(3);212-216
|                                            

The reptile that almost became a fish

07/08/2014 |

‘It’s head is as long as I am tall!’

       ‘What is it?’

‘Hmm…  A giant fish?  A lizard?  Don’t know.’

       ‘Well I know!  It’s a sea dragon!’ 

It is spring, 1811, the morning after a storm.  Mary is 12 years old, and fearless.  She edges across the cliff to where her brother is already working to free the fossil bones.  Fragments of weathered mudstone clatter down onto the beach.  The eye sockets of the huge skull are wider than the span of her hand.

A 185 million year old fossil of Ichthyosaurus acutirostris beside ammonites (Harpoceras falcifer). This specimen shows the distinctive downward (hypoocercal) bend of the spine into the lower tail fluke, characteristic of this reptile group. The outlines of the fluked tail and dorsal fin are visible; these were supported by cartilage rather than bone as in modern fish. The huge eye sockets (relative to its body size) enabled these animals to hunt by sight for shellfish, small fish and squid in dimly lit or murky waters (Image: Wikimedia Commons)

A 185 million year old fossil of Ichthyosaurus acutirostris beside ammonites (Harpoceras falcifer). This specimen shows the distinctive downward (hypoocercal) bend of the spine into the lower tail fluke, characteristic ... moreof this reptile group. The outlines of the fluked tail and dorsal fin are visible; these were supported by cartilage rather than bone as in modern fish. The huge eye sockets (relative to its body size) enabled these animals to hunt by sight for shellfish, small fish and squid in dimly lit or murky waters (Image: Wikimedia Commons)

During the 200 million years that dinosaurs roamed the land, the oceans were ruled by formerly land-dwelling reptiles.  Of these, ichthyosaurs adopted dolphin-like forms, plesiosaurs became sea lion-like, and mosasaurs occupied crocodile-like ‘ambush’ predator roles.

Of these, ichthyosaurs were arguably the most successful.  Their multiple adaptations to a fully aquatic life included huge eyes, a stiffened, fluked tail, and the ability to mate and give birth to live young in water.  Much as killer whales do today, these predators structured the marine ecosystem.  Many came to resemble the modern whales, dolphins and tuna fish that now fulfil similar ecological roles.  The convergence of body forms between some ichthyosaur species and tuna are particularly astonishing because these reptiles were air breathers.

Why did icthyosaurs evolve to look like modern marine animals?

Ichthyosaurs first colonised the sea 250Ma ago. The earliest known aquatic ichthyosaur, the otter-like Utatsusaurus hataii (top) fed on fish and shellfish in shallow water. After the Cretaceous-Tertiary mass extinction (65Ma), the land-based ancestors of modern whales also took to water. The early whale Kutchicetus minimus (middle) had an otter-like ecological role, and converged to evolve a similar body form. Both had an undulating swimming style which was in the horizontal plane (like an eel) for Utatsusarus, and vertical for Kutchicetus. This reflects the style of locomotion inherited from their respective ancestors (Images: Wikimedia Commons)

Ichthyosaurs first colonised the sea 250Ma ago. The earliest known aquatic ichthyosaur, the otter-like Utatsusaurus hataii (top) fed on fish and shellfish in shallow water. After the Cretaceous-Tertiary mass extinction ... more(65Ma), the land-based ancestors of modern whales also took to water. The early whale Kutchicetus minimus (bottom) had an otter-like ecological role, and converged to evolve a similar body form. Both had an undulating swimming style which was in the horizontal plane (like an eel) for Utatsusarus, and vertical for Kutchicetus. This reflects the style of locomotion inherited from their respective ancestors (Images: Wikimedia Commons)

Life in water poses a specific set of challenges.  These marine reptiles fulfilled similar ecological roles  to whales, and in time evolved body forms similar to these modern mammals.  This is known as convergence.

Like whales and tuna, ichthyosaurs were adapted for long distance energy-efficient swimming.  The respective horizontal and vertical strokes of both ichthyosaur and dolphin tails give an equally powerful ‘lift’ in both directions, propelling these animals forward in a near straight line.

A further example of this convergence is seen in the modern otter.  Unlike the Ichthyosaurs, both whales and otters had land-based mammalian ancestors with a vertically moving spine, giving them their bounding gait.  The whale-like ichthyosaurs moved their tail flukes horizontally, like a modern lizard.

Like whales and tuna, ichthyosaurs were adapted for long distance energy-efficient swimming.  The respective horizontal and vertical strokes of both ichthyosaur and  , propelling these animals forward in a near straight line.

What can modern animals tell us about ichthyosaurs?

The ichthyosaur Stenopterygius quadriscissus (above), became widespread, in the late Jurassic and early Cretaceous (160-100Ma). Its body shape is similar to that of the Bluefin tuna (Thunnus thynnus (below). Tuna hunt fish and squid at around 500m depth. This is possible because they have a high oxygen intake, fast metabolic rate, warm muscles, an energy efficient swimming style, and a higher heart rate and blood pressure than other fish (Images: Wikimedia Commons)

The ichthyosaur Stenopterygius quadriscissus (above), became widespread, in the late Jurassic and early Cretaceous (160-100Ma). Its body shape is similar to that of the Bluefin tuna (Thunnus thynnus (below). Tuna hunt f... moreish and squid at around 500m depth. This is possible because they have a high oxygen intake, fast metabolic rate, warm muscles, an energy efficient swimming style, and a higher heart rate and blood pressure than other fish (Images: Wikimedia Commons)

Modern tuna and lamnid sharks have converged into a similar ‘deep water sprint-predator’ ecological role.  These long distance migrants move constantly at a moderate speed, except for short fast bursts when chasing prey.  Chunky vertebrae stiffen their bodies at their core, reducing sideways movements except at the narrow ‘hinge’ before the tail.  The continuously active red ‘cruising’ muscles either side of the spine are warm, in marked contrast to most other fish.  In combination with large tendons, these muscles work like pulleys, flicking the fluked tail from side to side. The surrounding white muscles give extra power during short ‘sprints’.

The ichthyosaur Stenopterygius was tuna-shaped with chunky stacked vertebrae.  This stiffened body form suggests that these reptiles converged on the cruise-and-sprint deep water hunting role of modern tuna and lamnids.

Did ichthyosaurs have warm muscles like whales and tuna?

Cast of a skeleton of Hawkins’ plesiosaur (Thalassiodracon hawkinsi) from the Lower Lias strata at Street in Somerset; part of England’s Jurassic coast. These rocks are rich in marine fossils of all kinds including fish, ammonites and belemnites (Image: Wikimedia Commons)

Cast of a skeleton of Hawkins’ plesiosaur (Thalassiodracon hawkinsi) from the Lower Lias strata at Street in Somerset; part of England’s Jurassic coast. These rocks are rich in marine fossils of all kinds including ... morefish, ammonites and belemnites (Image: Wikimedia Commons)

The isotopic proportion between the heavy 18O and the light 16O oxygen (the ratio is given as d18O) in the bones of living fish and marine animals decreases as body temperature increases.  In principle we can use cold-blooded fish fossils as a ‘thermometer’ to indicate the water temperature, and compare this against isotope-predicted body temperatures for other fossil animals from the same rocks.

Oxygen isotope data allows us to infer that Jurassic plesiosaurs and ichthyosaurs had body temperatures of around 35⁰C, much higher than that of their environment.  This indicates that they could generate heat, and may well regulated their body temperatures independently of their environment (homeothermy).  Modern warm bodied marine animals have to conserve their body heat.  This means it is reasonable to infer that ichthyosaurs used similar methods such as a counter-current blood circulation  system and/or heat-insulating blubber.

What happened to the ichthyosaurs?

Plotosaurus bennisoni; a mosasaur from the Upper Cretaceous of North America. Most mososaurs lived in shallow coastal waters, although after the disappearance of the ichthyosaurs, some evolved into similar deep water sprint predators. Plotosaurus had crescent-shaped tail flukes, equipping this animal to whale-like fast pursuit behaviour (Image: Wikimedia Commons)

Plotosaurus bennisoni; a mosasaur from the Upper Cretaceous of North America. Most mososaurs lived in shallow coastal waters, although after the disappearance of the ichthyosaurs, some evolved into similar deep water sp... morerint predators. Plotosaurus had crescent-shaped tail flukes, equipping this animal to whale-like fast pursuit behaviour (Image: Wikimedia Commons)

Ichthyosaurs dominated the world’s oceans for around 150 million years, but then disappeared from the fossil record after the mid-Cretaceous (around 95Ma).  The cause of their sudden extinction remains a mystery.  The empty ecological roles that this created were later filled by mosasaurs; relatives of modern monitor lizards including the Komodo dragon.  In turn these reptiles died out during the Cretaceous-Tertiary mass extinction (65Ma), making way for the later evolution of modern whales, dolphins and tuna.

Text copyright © 2015 Mags Leighton. All rights reserved.

References
Benson, R.B.J. and Butler, R.J. (2011)  Uncovering the diversification history of marine tetrapods: ecology influences the effect of geological sampling biases In Comparing the Geological and Fossil Records: Implications for Biodiversity Studies ( A.J. McGowan and A.B.Smith, eds).  Geological Society of London Special Publications 358, 191-208.
Bernal, D. et al. (2005)  Mammal-like muscles power swimming in a cold-water shark.  Nature 437: 1349-1352.
Brill, R.W. (1996)  Selective advantages conferred by the high performance physiology of tunas, billfishes and dolphin fish.  Comparative Biochemistry and Physiology, A 113, 3-15.
Brill, R.W. et al.(2005)  Bigeye tuna (Thunnus obesus) behavior and physiology and their relevance to stock assessments and fishery biology.  Collective Volume of Scientific Papers ICCAT 57, 142-161.  Online;http://www.iccat.es/en/pubs_CVSP.htm
Dickson, K.A. and Graham, J.B. (2004)  Evolution and consequences of endothermy in fishes.  Physiological and Biochemical Zoology 77, 998-1018.
Donley, J.M. (2004)  Convergent evolution in mechanical design of lamnid sharks and tuna.  Nature 429, 61-65.
Fröbisch, N.B. et al. (2013)  Macropredatory ichthyosaur from the middle Triassic and the origin of modern trophic networks.  Proceedings of the National Academy of Sciences, USA 110, 1393-1397.
Graham, J.B. and Dickson, K.A. (2004)  Tuna comparative physiology. Journal of Experimental Biology 297, 4015-4024.
Houssaye, A. (2013)  Bone histology of aquatic reptiles: what does it tell us about secondary adaptation to an aquatic life?  Biological Journal of the Linnean Society 108, 3-21.
Korsmeyer, K.E. et al. (1996)  The aerobic capacity of tunas; adaptation for multiple metabolic demands.  Comparative Biochemistry and Physiology, A 113, 17-24.
Lindgren, J. et al. (2007) A fishy mosasaur: the axial skeleton of Plotosaurus (Reptilia, Squamata) reassessed. Lethaia 40,153–160.
Lindgren, J. et al. (2011)  Landlubbers to leviathans: evolution of swimming in mosasaurine mosasaurs.  Paleobiology 37, 445-469.
Lingham-Soliar, T. and Plodowski, G. (2007) Taphonomic evidence for high-speed adapted fins in thunniform ichthyosaurs. Naturwissenschaften 94, 65-70.
Malte, H. et al. (2007) Differential heating and cooling rates in bigeye tuna (Thunnus obesus Lowe); a model of non-steady heat exchange. Journal of Experimental Biology 210, 2618-2626.
Motani, R. et al. (1998) Ichthyosaurian relationships illuminated by new primitive skeletons from Japan.  Nature 393, 255-257.
Motani, R. (2002) Scaling effects in caudal fin propulsion and the speed of ichthyosaurs. Nature 415, 309-312.
Motani, R. (2002) Swimming speed estimation of extinct marine reptiles: energetic approach revisited. Palaeobiology 28, 251-262.
Motani, R. (2010) Warm-blooded “Sea Dragons”? Science 328, 1361-1362.
Rothschild, B. M. et al. (2012)  Adaptations for marine habitat and the effect of Triassic and Jurassic predator pressure on development of decompression syndrome in ichthyosaurs.  Naturwissenschaften 99, 443-448.
Syme, D.A. and Shadwick, R.E. (2011)  Red muscle function in stiff bodied swimmers: there and almost back again.  Philosophical Transactions of the Royal Society, B 366, 1507-1515.
Thewissen, J.G.M. and Bajpai, S. (2009)  New skeletal material of Andrewsiphius and Kutchicetus, two Eocene cetaceans from India.   Journal of Paleontology 83, 635-663.
|