In this article, i’m just taking forward some of the analysis of the Science paper on a draft sequence of the Neanderthal genome (Pääbo et al, 2010). Specifically i’m interested in the alleles which have the researchers suggest have been positively selected for in humans since the divergence from Neanderthal some 400,000 years ago. These alleles may perhaps tell us something about what makes humans unique. This preliminary analysis is rather superficial and simply consists of a more detailed description of the specified alleles together with speculation as appropriate. Excerpts are from Entrez Gene.
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’.
The gene products described here are therefore involved in development of the autonomic nervous system, regulation of insulin function, cerebral folate transport and neurodevelopment.
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.
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