title: Longevity and plasticity of CFTR provide an argument for noncanonical SNP organization in hominid DNA.
abstract: Like many other ancient genes, the cystic fibrosis transmembrane conductance regulator (CFTR) has survived for hundreds of millions of years. In this report, we consider whether such prodigious longevity of an individual gene--as opposed to an entire genome or species--should be considered surprising in the face of eons of relentless DNA replication errors, mutagenesis, and other causes of sequence polymorphism. The conventions that modern human SNP patterns result either from purifying selection or random (neutral) drift were not well supported, since extant models account rather poorly for the known plasticity and function (or the established SNP distributions) found in a multitude of genes such as CFTR. Instead, our analysis can be taken as a polemic indicating that SNPs in CFTR and many other mammalian genes may have been generated--and continue to accrue--in a fundamentally more organized manner than would otherwise have been expected. The resulting viewpoint contradicts earlier claims of 'directional' or 'intelligent design-type' SNP formation, and has important implications regarding the pace of DNA adaptation, the genesis of conserved non-coding DNA, and the extent to which eukaryotic SNP formation should be viewed as adaptive.
authors.affiliation: Department of Computer and Information Sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Aubrey E
authors.initials: AE
authors.lastname: Hill
authors.affiliation: Department of Biology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Zackery E
authors.initials: ZE
authors.lastname: Plyler
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Hemant
authors.initials: H
authors.lastname: Tiwari
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Amit
authors.initials: A
authors.lastname: Patki
authors.affiliation: Department of Computer and Information Sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Joel P
authors.initials: JP
authors.lastname: Tully
authors.affiliation: Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: McAtee
authors.affiliation: Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Leah A
authors.initials: LA
authors.lastname: Moseley
authors.affiliation: Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sorscher
mesh_terms: D000483:Alleles; D000818:Animals; D003550:Cystic Fibrosis / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D019143:Evolution, Molecular; D005091:Exons; D018703:Founder Effect; D005787:Gene Frequency; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D007438:Introns; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D044465:White People; D014998:Y Chromosome
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator