Tag Archives: HOXD8

What are the Implications of the Sequencing of the Neandertal Genome?

Neanderthal ManTwo Landmark Scientific Studies


In light of the recent sequencing of the Neanderthal Genome (60% complete), I thought it was a good opportunity to pause and reflect on what this means. Paablo and colleagues have in addition just announced at the recent Biology of Genomes 2010 conference that they have sequenced genome of the ‘unknown Hominin‘ sample from Siberia. Apparently it is not human and is more closely related to Neanderthal.  A previous analysis of the mitochondrial DNA suggests that we last shared a common ancestor with this Hominin 1 million years ago. What is remarkable is that this new Hominin species was found with ornaments including a bracelet and that the remains were dated to between 30,000 and 48,000 years ago.

With this sequencing of two of our nearest hominin relatives, we have an opportunity to learn a great deal about these hominins and also about ourselves. I think perhaps we are witnessing two landmark scientific studies and maybe when the dust settles they will be ranked alongside the discovery of DNA.

There are several big names who have specifically commented on (or participated in or both) this study that i’ve come across when reading around this subject – Paablo, Ed Green John Hawks, Chris Stringer,  Ed Willeserv, Clive Finlayson (if there are any names i’ve missed out let me know in the comments section) and they are interviewed or referenced in  Appendix 1 for those wanting to read around the subject.

Speculation


Given the gravitas of these two studies, I thought it would be a good opportunity to speculate. I am a psychiatrist and not a geneticist, anthropologist, comparative biologist, cognitive archaeologist or historian but commentary may pass into some of these areas given that the potential ramifications of these studies are so diverse. In terms of psychiatry, there are three immediate areas that it may be of relevance to  – genomics and evolutionary psychiatry but more on these later. I would also add that the proper discourse for the ramifications is within the peer-reviewed literature but within this medium it should be possible to at least begin a dialogue. It has often been said that the mark of good science is that the results pose more questions than are answered and that can certainly be argued to be the case here. I’m also asking some questions again quite superficially just as a starting point for discussion.

Were Neandertals A Different Species?


This is an important question for one very simple reason – technically if Neandertals were a different species then the offspring would be hybrids. This is also an area of controversy within the field with opposing views. One of the key features separating one species from another is the inability for the two species to produce offspring together. Obviously if Neandertals and humans did interbreed then this rule would be flouted. However there are additional criteria for a species which relate to morphological features amongst others. Here Neandertals and humans differ. However in response to morphological differences it can be argued that Neandertals have been shown to exhibit great diversity both according to region and to time period. Thus the sample size becomes very important in drawing robust conclusions and just as in a clinical trial a well-powered study with a comparator group consisting of either modern or archaic human specimens is needed.  Many of the differences noted have been criticised on the grounds that specimens may have become deformed either through pathology during their lifetime (e.g the old man of Chappelle-aux Saints) or after death. When differences are recognised it is usually suggested that they result from either adaptation to a cold climate in Europe or that they result from genetic drift. Here are some of the differences that have been noted.

  • Skull: Neandertals had a protruding area in their skull referred to as the occipital bun. However there are several groups of modern humans who exhibit this feature. (there is some evidence that this is associated with other cranial features).
  • Inner Ear: Differentiating features in the inner ear including larger malleus and closed angle between small and long processes of incus.
  • Hand: The Neandertal’s  little finger has markings suggestive of powerful attached musculature in this specimen – it was as strong as the other fingers
  • Femur: A low angle between the shaft and the neck.

In any case there is sufficient evidence to suggest that the human lineage initially diverged from our Neandertal concestor 300,000 years ago.  The evidence from Paabo’s group also suggests that we don’t share mitochondrial DNA with Neandertals. This must factor into any discussion on speciation. Indeed John Hawks has suggested that this results from selective pressures in the human lineage.

 

What if they Aren’t Separate Species?


Could interbreeding accelerate adaptation of one group? If there are two groups that have been isolated for 300,000 years and differences between the groups are assumed to be due to adaptation rather than genetic drift then wouldn’t admixture result in a rapid adaptation of the non-adapted group to the other group’s environment? Alternatively might it take both groups in a very different direction particularly if the networks of adaptive gene solutions are incompatible? I don’t know the answers to these questions.

What if they are Separate Species?

Then technically this would be called a hybridisation event.


How Could This Impact on Evolutionary Psychiatry and Psychology?

Although the principles of sexual and natural selection are invoked, the ‘Out of Africa’ hypothesis has provided a grand narrative suggesting successive waves of human migration out-of-africa without admixture. In terms of admixture, this means that the human population has been suddenly exposed to a significantly different gene pool. The genomic sequencing does suggest that there aren’t too many differences between human and neanderthal genomes but those differences exist within areas of significant biological function e.g homeobox genes. Therefore evolutionary models must incorporate two components

1. A progressive combination of adaptation and genetic drift in the human population with selection processes in action prior to the

2. A sudden and location specific admixture with a significantly different gene pool.

However it has been argued that with further sequencing of more samples – both Neanderthal and human – the positive allele selection identified from the selection sweep would be reduced and might even be zero. However this would still need to factor in consideration of the marked mDNA differences.

This means that evolutionary models may now have to factor in the psychological and biological attributes of the Neanderthals in understanding human psychology and illness. Additionally it is appearing likely that there may have been a large number of intelligent hominin species leaving Africa prior to our migration and with whom our ancestors came into contact with. This has been a blind spot in both wider culture and specifically in a number of evolutionary psychology/psychiatry models which is understandable given the limited available data.

In addition, the use of genetics adds another layer to the models that can now be developed. We can ask such interesting questions as

  • Did Neanderthals have an effect on the biology of human language? (they had FOXP2 genes and a high-pitched voice for instance).
  • What were the traits in mitochondrial DNA from Neanderthals that were completely selected out by humans? (if they did interbreed).
  • Which illnesses did Neanderthals bring into the human gene pool?
  • Was the rapid development of the Neanderthal brain in childhood a dominant trait?
  • Could this be associated with a chromosomal inversion found in 20% of Europeans?

What do the Positive Selected Alleles in Humans Show?

These are shown in more detail in Appendix 1. As John Hawks has commented in his article, we just don’t know enough about the biology of these genes yet to determine how this has impacted on human evolution. The reader is invited to look at the genes in Appendix 1 and follow the links before drawing their own conclusions. From my rather superficial inspection of the genes, I’ve noted the following. Firstly there are some very powerful genes that have apparently been selected for in humans. The Homeobox genes govern the shape of the developing body and may therefore have profound effects. Zinc finger proteins can alter the expression of other genes and might therefore be influencing several other genes and having complex effects. Interestingly and perhaps easier to understand, several of the selected alleles code for immune related proteins one of which is involved in Hepatitis C infections. Adaptation to viral infections would be a useful and inevitable part of the process of adaptation to any environment.

What Could the Effects of Interbreeding Have Been?

One point that has been neglected in much of the discussion is what effect could interbreeding have had on both human and neandertal cultures? If Neandertals and humans considered each other quite distinct then this could have had profound effects on both cultures.

One intriguing possibility is that if a hybridisation event took place it was significantly represented in both Aurignacian and Mousterian cultures. Along with the Venus figurine (curiously associated with fertility), the Lion man of Hohlenstein Stadl is one of the oldest known art works (note above that the Siberian hominin ornaments may predate this by a significant period). The figure has been described either as a man or a woman. The difficulty has arisen because of interpretation of the mane. However in Europe during that period, the Cave Lion on which it may have been modelled was prevalent and may not have had a mane. In any case the figure is also a hybrid with the head of a lion. This figure appears at other sites and is thought to have some significance. Although speculation, this may represent the culmination of thousands of years of verbal transmission of a story of ancestral interbreeding along with characteristics of the offspring.

From Wikimedia Commons

What is even more interesting, is that 25,000 years later the same lion headed figure (with intriguing associations) reappears prominently in several civilisations (e.g references can be found in the tomb of Tutankamun).

English: Tuthankamen's famous burial mask, on display in the Egyptian Museum in Cairo. Date 	  7 December 2003(2003-12-07) Source 	  Own work by uploader, http://bjornfree.com/galleries.html Author 	  Bjørn Christian Tørrissen Permission (Reusing this file) 	  See below.

Conclusions

Here, I am barely scraping the surface. For each gene below there is a significant amount of both literature research and experimental research that needs to take place in order to get a better understanding of what this all means. The sequencing of the genome will continue in order to get better coverage and reliability of results. Additionally many of the genes described in the study are associated with mental illnesses and the significance of this is as yet unclear.

Appendix 1

Chromosome 1

SELENBP1: ‘This gene product belongs to the selenium-binding protein family….It has been proposed that the effects of selenium in preventing …… neurologic diseases may be mediated by selenium-binding proteins’.

POGZ: ‘The protein encoded by this gene appears to be a zinc finger protein’.

MIR554: ‘microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs’.

RFX5: ‘A lack of MHC-II expression results in a severe immunodeficiency syndrome called MHC-II deficiency, or the Bare Lymphocyte Syndrome‘.

SNX27:  ‘A highly similar protein in mouse is responsible for the specific recruitment of an isoform of serotonin 5-hydroxytryptamine 4 receptor into early endosomes, suggesting the analogous role for the human protein’. This receptor is found in cells in the gut and heart.

CGN: From Entrez Gene it appears to have the following functions – Actin binding, protein binding, motor activity (‘Catalysis of movement along a polymeric molecule such as a microfilament or microtubule, coupled to the hydrolysis of a nucleoside triphosphate’).

TUFT1: Possible function in multiple tissues including tooth enamel.

PI4KB: Inositol phosphate metabolism, metabolic pathways and Phosphatidylinositol signaling system. There is also some research on the modification of the PI4KB gene produce in relation to Hepatitis C infection.

PSMB4:  ‘An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit’.

Chromosome 2


ZFP36L2: ‘This putative nuclear transcription factor most likely functions in regulating the response to growth factors’.

THADA: Thyroid adenoma associated. NIDDM association. ‘Common Variants in the Trichohyalin Gene Are Associated with Straight Hair in Europeans’. ‘Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate’.

EVX2: Even skipped Homeobox 2.  ’causes synpolydactyly, a dominantly inherited disease resulting in limb malformation’. There looks to be an interesting paper on this clinical condition here.

MTX2: ‘it is thought that the encoded protein is peripherally associated with the cytosolic face of the outer mitochondrial membrane, and that it is involved in the import of proteins into the mitochondrion’.

HOXD1: ‘This nuclear protein functions as a sequence-specific transcription factor that is involved in differentiation and limb development. Mutations in this gene have been associated with severe developmental defects on the anterior-posterior (a-p) limb axis’

HOXD3: ‘The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms’.

HOXD4: ‘The protein encoded by this gene may play a role in determining positional values in developing limb buds’.

HOXD8: ‘In addition to effects during embryogenesis, this particular gene may also play a role in adult urogenital tract function’.

HOXD9: ‘The exact role of this gene has not been determined’.

HOXD10: ‘Mutations in this gene have been associated with Wilm’s tumor and congenital vertical talus (also known as “rocker-bottom foot” deformity or congenital convex pes valgus and/or a foot deformity resembling that seen in Charcot-Marie-Tooth disease’.

HOXD11: ‘The product of the mouse Hoxd11 gene plays a role in forelimb morphogenesis’.

HOXD12: ‘The exact role of this gene has not been determined’.

HOXD13: ‘Mutations in this particular gene cause synpolydactyly’

MIR10B: ‘The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA’.

Chromosome 3


KCNAB1: ‘Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume’. ‘Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study’.

Chromosome 6


RUNX2: ‘This protein is essential for osteoblastic differentiation and skeletal morphogenesis and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer or, with more affinity, as a subunit of a heterodimeric complex. Mutations in this gene have been associated with the bone development disorder cleidocranial dysplasia (CCD)’. The researchers had suggested that a mutation in this gene would be consistent with some features seen in Neanderthals.

SUPT3H: Suppressor of Ty 3 homolog: ‘Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies’. ‘Identification of 15 loci influencing height in a Korean population’. ‘Many sequence variants affecting diversity of adult human height’.

BACH2: ‘Multiple common variants for celiac disease influencing immune gene expression’. ‘Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes’. ‘Genome-wide association scan of the time to onset of attention deficit hyperactivity disorder’.

Chromosome 7


INHBA: ‘The inhibin beta A subunit joins the alpha subunit to form a pituitary FSH secretion inhibitor’. ‘it is proposed that inhibin may be both a growth/differentiation factor and a hormone.’

RNF148: ring finger protein 148.’(Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the ‘cross-brace’ motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in mediating protein-protein interactions; identified in a proteins with a wide range of functions such as viral replication, signal transduction, and development’.

RNF133: See RNF148.

CADPS2: ‘This gene encodes a member of the calcium-dependent activator of secretion (CAPS) protein family, which are calcium binding proteins that regulate the exocytosIs of synaptic and dense-core vesicles in neurons and neuroendocrine cells. Mutations in this gene may contribute to autism susceptibility’.

Chromosome 10


RHOBTB1:  ‘Genome-wide association study identifies eight loci associated with blood pressure’.

NRG3:  ‘This gene encodes neuregulin 3 (NRG3). NRG3 has been shown to activate the tyrosine phosphorylation of its cognate receptor, ERBB4, and is thought to influence neuroblast proliferation, migration and differentiation by signalling through ERBB4. NRG3 also promotes mammary differentiation during embryogenesis. Linkage studies have implicated this gene as a susceptibility locus for schizophrenia and schizoaffective disorder’.

BICC1: ‘This gene encodes an RNA-binding protein that is active in regulating gene expression by modulating protein translation during embryonic development’.

Chromosome 11

JRKL: ‘The function of this gene has not yet been defined, however, the encoded protein shares similarity with the human (41% identical) and mouse (34% identical) jerky gene products. This protein may act as a nuclear regulatory protein’. Phenotypes: ‘Epilepsy, childhood absence, evolving to juvenile myoclonic epilepsy’.

CCDC82: coiled-coil domain containing 82. This is protein coding but the function does not yet appear to have been characterised.

MAML2: MAML2 mastermind-like 2. Phenotypes – Mucoepidermoid salivary gland carcinoma.

CLPB: I couldn’t find a reference to humans but in the Chimpanzee this is a ‘ClpB caseinolytic peptidase B homolog’.

FOLR1: Phenotypes – ‘?Congenital anomalies, susceptibility to’, ‘Neurodegeneration due to cerebral folate transport deficiency’. Function: Folic acid binding. Receptor activity. Process: folic acid metabolic process. Folic acid transport. Receptor-mediated endocytosis. Component: Anchored to plasma membrane. Brush border. Extracellular region. Integral to plasma membrane. Membrane fraction. Plasma membrane. The protein encoded by this gene is a member of the folate receptor family. Members of this gene family bind folic acid and its reduced derivatives, and transport 5-methyltetrahydrofolate into cells. This gene product is a secreted protein that either anchors to membranes via a glycosyl-phosphatidylinositol linkage or exists in a soluble form. Mutations in this gene have been associated with neurodegeneration due to cerebral folate transport deficiency.

PHOX2A: ‘The protein encoded by this gene contains a paired-like homeodomain most similar to that of the Drosophila aristaless gene product. The encoded protein plays a central role in development of the autonomic nervous system. It regulates the expression of tyrosine hydroxylase and dopamine beta-hydroxylase, two catecholaminergic biosynthetic enzymes essential for the differentiation and maintenance of the noradrenergic neurotransmitter phenotype. The encoded protein has also been shown to regulate transcription of the alpha3 nicotinic acetylcholine receptor gene. Mutations in this gene have been associated with autosomal recessive congenital fibrosis of the extraocular muscles’. Function: ‘Our 16-patient sample suggests that KIF21A and PHOX2A sequence variation does not have a role in common forms of congenital incomitant vertical strabismus’. ‘The ARIX 153G>A polymorphism might be a genetic risk factor for the development of congenital superior oblique muscle palsy’. ‘PHOX2A and PHOX2B genes are highly co-expressed in human neuroblastoma’.

FOLR2:  ‘The protein encoded by this gene is a member of the folate receptor (FOLR) family, and these genes exist in a cluster on chromosome 11. Members of this gene family have a high affinity for folic acid and for several reduced folic acid derivatives, and they mediate delivery of 5-methyltetrahydrofolate to the interior of cells’. ‘Although this protein was originally thought to be specific to placenta, it can also exist in other tissues, and it may play a role in the transport of methotrexate in synovial macrophages in rheumatoid arthritis patients’. Function: Folic acid binding. Receptor activity. Process: Folic acid transport. Component: Anchored to membrane. Extracellular region. Membrane fraction. Plasma membrane.

INPPL1: ‘The protein encoded by this gene is an SH2-containing 5′-inositol phosphatase that is involved in the regulation of insulin function. The encoded protein also plays a role in the regulation of epidermal growth factor receptor turnover and actin remodelling. Additionally, this gene supports metastatic growth in breast cancer’.

Chromosome 14


MIR337: microRNA 337. ‘microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs’.

MIR665: microRNA 665. see MIR 337. microRNA 431. See MIR 337 for general information.

DLK1: Delta-like 1 homolog. ‘This gene encodes a transmembrane protein containing six epidermal growth factor repeats. The protein is involved in the differentiation of several cell types, including adipocytes; it is also thought to be a tumor suppressor’. ‘A polymorphism within this gene has been associated with child and adolescent ‘. obesity.

RTL1: Retrotransposon-like 1. ‘This gene is a retrotransposon-derived, paternally expressed imprinted gene that is highly expressed at the late fetal stage in both the fetus and placenta. It has an overlapping maternally expressed antisense transcript, which contains several microRNAs targeting the transcripts of this gene through an RNA interference (RNAi) mechanism. This gene is essential for maintenance of the fetal capillaries’. Process: Multicellular organismal development. Component: Integral to membrane. Membrane.

MIR431: microRNA 431. See MIR 337 for general information. Specific function doesn’t appear to be characterised.

MIR493: microRNA 493. See MIR 337 for general information. Specific function doesn’t appear to be characterised.

MEG3: maternally expressed 3. ‘MEG3 is a maternally expressed imprinted gene which appears to function as an RNA molecule; multiple splice variants are observed in the available sequence data and a pituitary transcript variant has been associated with inhibited cell proliferation’. ‘The expression profile in mouse of the co-regulated Meg3/Gtl2 and Dlk1 genes suggests a causative role in the pathologies found in uniparental disomy animals, characterized by defects in skeletal muscle maturation, bone formation, placenta size and organization, and prenatal lethality’.

MIR770: microRNA 770. See MIR 337 for general information. Specific function doesn’t appear to be characterised.

Chromosome 21


DYRK1A: dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A. ‘It may play a significant role in a signaling pathway regulating cell proliferation and may be involved in brain development. This gene is a homolog of Drosophila mnb (minibrain) gene and rat Dyrk gene. It is localized in the Down syndrome critical region of chromosome 21′. Function: ATP-binding. Non-membrane spanning protein tyrosine kinase activity. Nucleotide binding. Protein binding. Protein kinase activity. Protein self-assocation. Protein serine/threonine kinase activity. Protein tyrosine kinase activity. Transferase activity. Process: Nervous system development. Peptidyl-tyrosine phosphorylation. Peptidyl-tyrosine phosphorylation. Protein aminoa acid autophosphorylation. Protein amino acid phosphorylation. Component: Nuclear speck. Nucleus.

Appendix 2Online Newspapers, Blogs and Websites referencing the study


  • BBC – interview with Professor Finlayson.
  • Bristol University – brief article with useful links to research on possible human-neanderthal interbreeding.
  • Christian Science Monitor – discussion including comparison of Neanderthal, chimpanzee and humans.
  • Dienekes Anthropology Blog – detailed article arguing against admixture with lots of comments.
  • The Economist – Turning Point in our in understanding of ourselves through genome sequencing.
  • Half-Sigma – brief article with discussion and lots of comments.
  • John Hawks Blog – Detailed explanation of the possible Neanderthal contribution to the human genome.
  • Lawrence Journal.com – brief article with reference to illness.
  • Mathilda’s Anthropology blog – brief article with lots of comments.
  • Mind Hacks – brief mention here.
  • Oregon Live.com – brief tongue-in-cheek take on what an early Neanderthal-Human encounter may have been like.
  • The Washington Post – brief article with references to illness.
  • Trueslant.com – comment on Earth’s Children fiction book about human raised by Neandertals.
  • USA Today – discussion of myths and drawing an analogy between Hercules and the Neandertal.
  • Wired – brief article which refers to possible skeletal evidence of interbreeding.

Podcasts

Appendix 3 – Other Resources including Research Papers


  • Critique of Neanderthal predator theory.
  • PNAS paper on methodology for evaluating adaptive properties of Neandertal skulls.
  • Evidence that Shanidar 3 Neandertal sustained injuries from a low kinetic energy object.
  • Questioning the cold climate adaptation hypothesis of large Neandertal chests.
  • Dating of Belgian specimens.
  • Investigation of nasal aperture in Neandertals and cold adaptation.
  • Analysis of Italian early Neandertal Saccopastore 1 specimen
  • Analysis of thorax in Neandertals and humans and suggestion that this relates to activity levels in Neandertals.
  • Working memory and cognition in Neandertal (here and here).
  • Analysis of Peche De L’Aze 1 Neandertal child.
  • Analysis of Spanish Neandertal specimen.
  • Evidence of human/Neandertal admixture.
  • Analysis of a Spanish Neandertal mandible.
  • An article looking back at 150 years since the recogntion of the Neandertal.
  • Bite force varies according to size in both Neandertals and humans rather and not between the two.
  • Discussion of Mental Foramen in Neandertal and humans.
  • Paabo PNAS study on examination of Neander Valley specimens.
  • Article on cold adaptation. ‘it is estimated that Neandertals required 3,360 to 4,480 kcal per day to support strenuous winter foraging and cold resistance costs’.
  • Shanidar 3 and thoracic morphology in the Neandertal.
  • Isotope analysis suggesting that Neandertal diet consisted of herbivores.
  • Greater moment in the knees of Neandertals in the locomotor range compared to humans.
  • Analysis of the pelvis of two Israeli Neandertal specimens
  • The dentition of the old man of Chapelle-aux-saints.

Appendix 4

Miscellaneous news articles on Neandertals

Videos


  • 2007 ITN news report on Neanderthal mitochondrial DNA sequencing.
  • Reconstruction of the musculature. Great quote – ‘the pinky was just as strong as the other fingers’.
  • Recreating the Neanderthal face. Great quote – ‘This Neanderthal did not have a waist’.
  • Interview with John Hawks. Notes that over 400 Neanderthal skeletons have been found.
  • Footage of the cave in Vindija, Croatia.
  • Interview with John Hawks on the possible complexities of the Neanderthal-Human interactions.

Appendix 5

Review of John Hawks Blog (see here also)

Hawks has a special interest in Neanderthals (or Neandertals as he prefers in this spelling debate) and he talks about them in this interview as well as in a number of other posts. Indeed the posts in which he discusses Neanderthals are extensive and this list is by no means exhaustive although it will become apparent that there are certain themes. An understanding of Neanderthals has come about through two broad approaches – the study of Neanderthal fossils (with associated tools and fauna) and the study of DNA (including mitochondrial DNA). There are an abundance of interesting posts about the genetic analysis of Neanderthals including the methylation of Neanderthal DNA, the El Sidron specimen mitochondrial DNA extraction, the Mitochondria Neanderthal story parts 1 and 2 ,  commentary on Neanderthal mitochondrial DNA here and here, mitochondrial DNA adaptations in modern humans, the Neanderthal genome FAQ 2009, Neanderthal genome FAQs, . There are also numerous posts examining the many aspects of analysis of fossilised Neanderthal speciments: A discussion of a recent understanding of the structure of the Neanderthal ribcage, forensic analysis of a Shanidar specimen, dredging of a Neanderthal specimen from the North Sea, discussion of a Neanderthal mandible at an Aurignacian site with the implications,  the Lakonis Greek individual, the Neanderthal vocal tract , protein content of Neanderthal bones, muscle differences between humans, chimpanzees and Neanderthals, the El Sidron Neanderthal’s O group blood type, pigment use and symbolic behaviour, differences between Neanderthal populations, body mass, CBLM volume, the marine diet of Neanderthals, more on Neanderthal mobility, elephant hunting Neanderthals, Gorham’s cave, shellfish, nitrous oxide in Neanderthal sinuses, dental analysis of Croatian specimens and inference of lifespan, Neanderthals and red hair, a 120,000 year old Neanderthal hut, a discussion of the crossing of the Gibraltar strait, dating the Croatian specimens , comparison of human, Neanderthal and other hominid teeth , further discussion of Neanderthal teeth including the development of the Neanderthal teeth , nitrogen isotope dating and Neanderthals , hunting 12 foot camels ,  the mandibular ramus of Neanderthals, radiocarbon dating of Chatelperronnitrogen isotope dating and fish consumption (which can confound dating analysis), neanderthals and mammoths and dating the Mladec site.

There are a number of posts discussing high level concepts which move further from the data but which provide a richer perspective on Neanderthals in terms of behaviour or longer term population effects: Evidence of reduced Neanderthal mitochondrial DNA diversity over time, a discussion of genetic introgression, the 17q21.31 inversion and a discussion of introgression in relation to the Neanderthal genome, a number of other posts on introgression focusing on FOXP2, microcephalin FAQ’s and general issues on Neanderthal introgression (and here), ethical issues, interpretations of Neanderthals on the basis of multiple studies, genetic drift versus natural selection, myths of Neanderthals, Neanderthals and Kuru, Neanderthals and heat loss, gender and Neanderthal hunting and here and here, reconstruction of possible Neanderthal music, more on talking Neanderthals here, discussion of Neanderthal language here, comparing brown bear and Neanderthal colonisation, colonisation of arctic Europe (argument that this was humans), Pleistocene Europe as a population sink, New World founders, the Toba bottleneck, review of bottleneck studies, one interpretation of human and Neanderthal encounters, dental analysis of Qafzeh specimens (possibly not Neanderthal), 50,000 year old bedding material in a Georgian cave discussed here. Neanderthal extinction by competitive exclusion, coexistence with humans, the human revolution, an epic post on human expansion, report on a conference, the opening of the Krapina Neanderthal museum, analogies with Baboons and more on Neanderthal mobility are discussed in these posts.

References

A Draft Sequence of the Neandertal Genome.Richard E. Green, Johannes Krause, Adrian W. Briggs, Tomislav Maricic,  Udo Stenzel, Martin Kircher, Nick Patterson,  Heng Li, Weiwei Zhai,  Markus Hsi-Yang Fritz, Nancy F. Hansen, Eric Y. Durand, Anna-Sapfo Malaspinas, Jeffrey D. Jensen, Tomas Marques-Bonet, Can Alkan, Kay Prüfer, Matthias Meyer, Hernán A. Burbano, Jeffrey M. Good, Rigo Schultz, Ayinuer Aximu-Petri,  Anne Butthof, Barbara Höber, Barbara Höffner,  Madlen Siegemund, Antje Weihmann, Chad Nusbaum,  Eric S. Lander, Carsten Russ, Nathaniel Novod,  Jason Affourtit, Michael Egholm, Christine Verna, Pavao Rudan, Dejana Brajkovic,  Zeljko Kucan, Ivan Gusic,  Vladimir B. Doronichev, Liubov V. Golovanova,  Carles Lalueza-Fox, Marco de la Rasilla, Javier Fortea,  Antonio Rosas, Ralf W. Schmitz,  Philip L. F. Johnson, Evan E. Eichler, Daniel Falush, Ewan Birney, James C. Mullikin, Montgomery Slatkin, Rasmus Nielsen, Janet Kelso, Michael Lachmann, David Reich,Svante Pääbo. Science 7 May 2010:Vol. 328. no. 5979, pp. 710 – 722.

Friedemann Schrenk and Stephanie Muller in collaboration with Christine Hemm. Translated by Phyllis Jestice. The Neanderthals. Routledge – Taylor and Francis Group. Kindle Edition. 2009.

Acknowledgements

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A Draft Sequence of the Neanderthal Genome: Review – 2nd Part

Chromosome 2

Continuing with a rather superficial analysis of some of the alleles that the research team suggested had been positively selected for in the human lineage since divergence from the Neanderthal 400,000 years ago. These alleles may give insights into important aspects of human evolution over the last 400,000 years. Excerpts are from Entrez Gene.

ZFP36L2: ‘This putative nuclear transcription factor most likely functions in regulating the response to growth factors’. Speculation: Difficult without more information.

THADA: Thyroid adenoma associated. NIDDM association. ‘Common Variants in the Trichohyalin Gene Are Associated with Straight Hair in Europeans’. ‘Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate’. Speculation: Although there were a number of associations, I wasn’t clear on what the function of THADA is.

EVX2: Even skipped Homeobox 2.  ’causes synpolydactyly, a dominantly inherited disease resulting in limb malformation’. There looks to be an interesting paper on this clinical condition here. Speculation: As with other homeobox associated and homeobox genes this will relate to morphology.

MTX2: ‘it is thought that the encoded protein is peripherally associated with the cytosolic face of the outer mitochondrial membrane, and that it is involved in the import of proteins into the mitochondrion’. Speculation: Difficult without more information.

HOXD1: ‘This nuclear protein functions as a sequence-specific transcription factor that is involved in differentiation and limb development. Mutations in this gene have been associated with severe developmental defects on the anterior-posterior (a-p) limb axis’

HOXD3: ‘The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms’.

HOXD4: ‘The protein encoded by this gene may play a role in determining positional values in developing limb buds’.

HOXD8: ‘In addition to effects during embryogenesis, this particular gene may also play a role in adult urogenital tract function’.

HOXD9: ‘The exact role of this gene has not been determined’.

HOXD10: ‘Mutations in this gene have been associated with Wilm’s tumor and congenital vertical talus (also known as “rocker-bottom foot” deformity or congenital convex pes valgus and/or a foot deformity resembling that seen in Charcot-Marie-Tooth disease’. Speculation: May be associated with efficiency of locomotion – a noted difference between humans and neanderthals.

HOXD11: ‘The product of the mouse Hoxd11 gene plays a role in forelimb morphogenesis’.

HOXD12: ‘The exact role of this gene has not been determined’.

HOXD13: ‘Mutations in this particular gene cause synpolydactyly’

MIR10B: ‘The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA’.

Conclusions

It looks as though a number of Homeobox alleles have been conserved across humans over the past 400,000 years. Perhaps there are strong selection effects for morphology and this may relate to notions of body image. The mechanisms governing the appearance of hair as well as characteristics of locomotion may also be features that have been conserved across humans since divergence from Neanderthal.

References

A Draft Sequence of the Neandertal Genome.Richard E. Green, Johannes Krause, Adrian W. Briggs, Tomislav Maricic,  Udo Stenzel, Martin Kircher, Nick Patterson,  Heng Li, Weiwei Zhai,  Markus Hsi-Yang Fritz, Nancy F. Hansen, Eric Y. Durand, Anna-Sapfo Malaspinas, Jeffrey D. Jensen, Tomas Marques-Bonet, Can Alkan, Kay Prüfer, Matthias Meyer, Hernán A. Burbano, Jeffrey M. Good, Rigo Schultz, Ayinuer Aximu-Petri,  Anne Butthof, Barbara Höber, Barbara Höffner,  Madlen Siegemund, Antje Weihmann, Chad Nusbaum,  Eric S. Lander, Carsten Russ, Nathaniel Novod,  Jason Affourtit, Michael Egholm, Christine Verna, Pavao Rudan, Dejana Brajkovic,  Zeljko Kucan, Ivan Gusic,  Vladimir B. Doronichev, Liubov V. Golovanova,  Carles Lalueza-Fox, Marco de la Rasilla, Javier Fortea,  Antonio Rosas, Ralf W. Schmitz,  Philip L. F. Johnson, Evan E. Eichler, Daniel Falush, Ewan Birney, James C. Mullikin, Montgomery Slatkin, Rasmus Nielsen, Janet Kelso, Michael Lachmann, David Reich,Svante Pääbo. Science 7 May 2010:Vol. 328. no. 5979, pp. 710 – 722.

Acknowledgements

Picture of Chromosome 2 from Wikimedia Commons and originally from the National Institute of Health. It is in the Public Domain.

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