A Draft Sequence of the Neanderthal Genome – Review Part 3

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.

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’.

There are a number of genes here that are associated with illnesses including ADHD, Schizophrenia, Schizoaffective Disorder, Autism as well as regulation of height and an association with cleidocranial dysplasia the authors have drawn attention to most of these associations in the paper. These associations will benefit from further reflection.

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.

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37 thoughts on “A Draft Sequence of the Neanderthal Genome – Review Part 3

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