Human type I hair keratin pseudogene ϕhHaA has functional orthologs in the chimpanzee and gorilla: evidence for recent inactivation of the human gene after the Pan-Homo divergence

  title={Human type I hair keratin pseudogene ϕhHaA has functional orthologs in the chimpanzee and gorilla: evidence for recent inactivation of the human gene after the Pan-Homo divergence},
  author={Hermelita Winter and Lutz Langbein and Michael Krawczak and David N. Cooper and Luis Felipe Jave-Su{\'a}rez and Michael A. Rogers and Silke Praetzel and Peter J. Heidt and Jürgen Schweizer},
  journal={Human Genetics},
Abstract. In addition to nine functional genes, the human type I hair keratin gene cluster contains a pseudogene, ϕhHaA (KRTHAP1), which is thought to have been inactivated by a single base-pair substitution that introduced a premature TGA termination codon into exon 4. Large-scale genotyping of human, chimpanzee, and gorilla DNAs revealed the homozygous presence of the ϕhHaA nonsense mutation in humans of different ethnic backgrounds, but its absence in the functional orthologous chimpanzee… 

Identification of nine human-specific frameshift mutations by comparative analysis of the human and the chimpanzee genome sequences

This study demonstrates that even the unfinished chimpanzee genome sequence can be useful in identifying modification of genes that are specific to the human lineage and, therefore, could potentially be relevant to the study of the acquisition of human-specific traits.

An Exon-Based Comparative Variant Analysis Pipeline to Study the Scale and Role of Frameshift and Nonsense Mutation in the Human-Chimpanzee Divergence

  • GongXin Yu
  • Biology
    Comparative and functional genomics
  • 2009
ExonVar is reported, a novel computational pipeline for Exon-based human-chimpanzee comparative Variant analysis that revealed a number of sequencing errors in the chimpanzee and human genome sequences and further illustrated that they could be corrected without resequencing.

The human type I keratin gene family: characterization of new hair follicle specific members and evaluation of the chromosome 17q21.2 gene domain.

In general concurrence with recent studies, bioinformatic analysis of the chromosome 17q21.2 DNA sequence shows that all of the 27 keratin genes found on this domain have been characterized at the transcriptional level, and this seems to be the entire complement of functional type I keratins in humans.

Differences between human and chimpanzee genomes and their implications in gene expression, protein functions and biochemical properties of the two species

This review summarized the available information about genetic differences between humans and chimpanzees and their potential functional impacts on differential molecular, anatomical, physiological and cognitive peculiarities of these species.

Evolution of the phosphoglycerate mutase processed gene in human and chimpanzee revealing the origin of a new primate gene.

Evidence that PGAM3 likely produces a functional protein is found, as an example of addressing functionality for human processed pseudogenes, and interspecies and intraspecies variation forPGAM3 was not consistent with the neutral model proposed for pseudogene, suggesting that a new functional primate gene has originated.

Duplication and positive selection among hominin-specific PRAME genes

It is predicted that PRAME genes evolved adaptively due to strong competition between rapidly-dividing cells during spermatogenesis and oogenesis, and it is suggested that as PRAME gene copy number is polymorphic among individuals, positive selection of PRAME alleles may still prevail within the human population.

Genes for intermediate filament proteins and the draft sequence of the human genome: novel keratin genes and a surprisingly high number of pseudogenes related to keratin genes 8 and 18.

The limits of the analysis are described, the striking unevenness of pseudogene derivation in the IF multigene family is discussed and the nomenclature of Moll and colleagues is proposed to extend to any novel keratin.

Understanding the recent evolution of the human genome: insights from human–chimpanzee genome comparisons

Recent progress in comparing the human and chimpanzee genomes is reviewed and how the differences detected have improved the understanding of the evolution of the human genome is discussed.

Genome-wide analysis of chimpanzee genes with premature termination codons

The results showed that the density of PTC genes fluctuated across the genome depending on the local genomic context, and PTCs were preferentially located in the terminal parts of the transcript, which generally have a lower frequency of functional domains, indicating that selection was operating against P TCs at sites central to protein function.

Molecular characterization of the pericentric inversion that causes differences between chimpanzee chromosome 19 and human chromosome 17.

The findings suggest that repeat-mediated nonhomologous recombination has facilitated inversion formation in chimpanzee chromosome 19, and this inversion affects neither the genomic structure nor the gene-activity state with regard to replication timing of these genes.



The region coding for the helix termination motif and the adjacent intron 6 of the human type I hair keratin gene hHa2 contains three natural, closely spaced polymorphic sites.

Sequence comparisons of the HTR of hHa2 with those of other type I hair keratins including the h Ha2-ortholog from chimpanzee provide evidence that the P1- and P2-linked mutations must have occurred very early in human evolution and that the two P2 -associated codon variants may be the result of two independent point mutations in an ancestral AGC serine codon.

Characterization of a 190-Kilobase Pair Domain of Human Type I Hair Keratin Genes*

Evolutionary tree construction reveals an early divergence of hair keratin genes from cytokeratin genes, followed by the segregation of the genes into the three subclusters of tandemly arranged genes.

Sequence data and chromosomal localization of human type I and type II hair keratin genes.

A cDNA library constructed with poly(A)+ RNA from human scalp was screened with selected fragments of both murine type I and type II hair keratin cDNAs, revealing an orthologous relationship between the largest member of the type II wool keratin subfamily, K2.9-12, and the phKI-2 encoded keratin hHa2.

Characterization of a 300 kbp region of human DNA containing the type II hair keratin gene domain.

Reverse transcription-polymerase chain reaction shows that all hair keratin genes are expressed in the hair follicle, and it is assumed that the approximately 200 kbp DNA domain contains the entire complement of human type II hair Keratin genes.

A mutation in human CMP-sialic acid hydroxylase occurred after the Homo-Pan divergence.

Cloning of human and chimpanzee hydroxylase cDNAs indicates that the lineage leading to modern humans suffered a mutation sometime after the common ancestor with the chimpanzee and bonobo, potentially affecting recognition by a variety of endogenous and exogenous sialic acid-binding lectins.

X chromosome evidence for ancient human histories.

  • E. HarrisJ. Hey
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
Diverse African and non-African samples of the X-linked PDHA1 (pyruvate dehydrogenase E1 alpha subunit) locus revealed a fixed DNA sequence difference between the two sample groups, suggesting the transformation to modern humans occurred in a subdivided population.

Analysis of mtDNA variation in African populations reveals the most ancient of all human continent-specific haplogroups.

Comparison of the intrapopulation sequence divergence in African and non-African populations confirms that African populations exhibit the largest extent of mtDNA variation, a result that further supports the hypothesis that Africans represent the most ancient human group and that all modern humans have a common and recent African origin.

Sequential Loss of Two Neighboring Exons of the Tropoelastin Gene During Primate Evolution

A sequential loss of exons 34 and 35 during primate evolution was probably facilitated by Alu-mediated recombination events and possibly conferred a functional evolutionary advantage in elastic tissue.

Molecular phylogeny of the hominoids: inferences from multiple independent DNA sequence data sets.

  • M. Ruvolo
  • Biology
    Molecular biology and evolution
  • 1997
The multiple-locus test (Wu 1991), which evaluates hypotheses using gene tree-species tree mismatch probabilities in a likelihood ratio test, favors the phylogeny with a Homo-Pan clade and rejects the other alternatives with a P value of 0.002: the problem of hominoid phylogeny can be confidently considered solved.

DNA sequence variation in a non-coding region of low recombination on the human X chromosome

10 kb of non-coding DNA is sequenced in a region of low recombination at Xq13.3 to provide more answers about the genetic origin and history of humans.