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Cited by 121Skin and Cellular Biology ResearchGenomics and Phylogenetic StudiesChromosomal and Genetic Variations

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Molecular evolution of the keratin associated protein gene family in mammals, role in the evolution of mammalian hair

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Wu, Dong-Dong, Irwin, David M, Zhang, Ya-Ping·2008·BMC Evolutionary Biology
DOI 10.1186/1471-2148-8-241PMC PMC2528016
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Abstract

Background: Hair is unique to mammals. Keratin associated proteins (KRTAPs), which contain two major groups: high/ultrahigh cysteine and high glycine-tyrosine, are one of the major components of hair and play essential roles in the formation of rigid and resistant hair shafts. Results: The KRTAP family was identified as being unique to mammals, and near-complete KRTAP gene repertoires for eight mammalian genomes were characterized in this study. An expanded KRTAP gene repertoire was found in rodents. Surprisingly, humans have a similar number of genes as other primates despite the relative hairlessness of humans. We identified several new subfamilies not previously reported in the high/ultrahigh cysteine KRTAP genes. Genes in many subfamilies of the high/ultrahigh cysteine KRTAP genes have evolved by concerted evolution with frequent gene conversion events, yielding a higher GC base content for these gene sequences. In contrast, the high glycine-tyrosine KRTAP genes have evolved more dynamically, with fewer gene conversion events and thus have a lower GC base content, possibly due to positive selection. Conclusion: Most of the subfamilies emerged early in the evolution of mammals, thus we propose that the mammalian ancestor should have a diverse KRTAP gene repertoire. We propose that hair content characteristics have evolved and diverged rapidly among mammals because of rapid divergent evolution of KRTAPs between species. In contrast, subfamilies of KRTAP genes have been homogenized within each species due to concerted evolution.

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Figures

Figure 1 Summary of the evolution of the KRTAP gene repertoires in eight mammals. Major events in the evolution of the KRTAP gene family are summarized. The number of KRTAP genes in each species is indicated on the right with "all", "HS", and "HGT" indicating patterns for all, high/ultrahigh cysteine, and high glycine-tyrosine KRTAPs, respectively. The columns represent the numbers of intact, interrupted and all genes and the percentage of pseudogenization calculated as the ratio of number of disrupted gene to all genes, for each of the categories of genes. Stars in the phylogeny indicate the origin of subfamilies, while circles indicate losses.
Figure 1 Summary of the evolution of the KRTAP gene repertoires in eight mammals. Major events in the evolution of the KRTAP gene family are summarized. The number of KRTAP genes in each species is indicated on the right with "all", "HS", and "HGT" indicating patterns for all, high/ultrahigh cysteine, and high glycine-tyrosine KRTAPs, respectively. The columns represent the numbers of intact, interrupted and all genes and the percentage of pseudogenization calculated as the ratio of number of disrupted gene to all genes, for each of the categories of genes. Stars in the phylogeny indicate the origin of subfamilies, while circles indicate losses.CC BY · PubMed Central
Figure 2 Phylogenetic tree of high glycine-tyrosine KRTAP genes of all mammals. Simplified phylogeny of all of the high glycine-tyrosine KRTAP genes generated by the neighbor-joining algorithm using p-distances. Genes of each subfamily are represented by different colors. Numbers on branches are the reliabilities of the branches which are calculated by interior branch tests with 1,000 replications. The bars indicate six subfamilies (6, 7, 8, 19, 20 and 21) of HGT-KRTAP genes.
Figure 2 Phylogenetic tree of high glycine-tyrosine KRTAP genes of all mammals. Simplified phylogeny of all of the high glycine-tyrosine KRTAP genes generated by the neighbor-joining algorithm using p-distances. Genes of each subfamily are represented by different colors. Numbers on branches are the reliabilities of the branches which are calculated by interior branch tests with 1,000 replications. The bars indicate six subfamilies (6, 7, 8, 19, 20 and 21) of HGT-KRTAP genes.CC BY · PubMed Central
Figure 3 Summary of the chromosomal distribution of KRTAP genes in the human genomes. The relative genomic location of each KRTAP gene is shown for chromosomes 2, 11, 17 and 21. Each gene, and distances between genes are not to scale. Arrowheads indicate the direction of transcription. The clusters are also labeled.
Figure 3 Summary of the chromosomal distribution of KRTAP genes in the human genomes. The relative genomic location of each KRTAP gene is shown for chromosomes 2, 11, 17 and 21. Each gene, and distances between genes are not to scale. Arrowheads indicate the direction of transcription. The clusters are also labeled.CC BY · PubMed Central
Figure 4 Correlation between GC (Guanine and Cytosine) content and divergence between KRTAP genes. The synonymous substitution rates (dS) among paralogs within each subfamily and codon GC content (GC%) (A) and third codon GC content (GC3%) (B) of each subfamily is plotted. Dots and circles represent high cysteine KRTAP (HS) and high glycine-tyrosine KRTAP (HGT), respectively. The linear regression formulae for GC and dS are shown.
Figure 4 Correlation between GC (Guanine and Cytosine) content and divergence between KRTAP genes. The synonymous substitution rates (dS) among paralogs within each subfamily and codon GC content (GC%) (A) and third codon GC content (GC3%) (B) of each subfamily is plotted. Dots and circles represent high cysteine KRTAP (HS) and high glycine-tyrosine KRTAP (HGT), respectively. The linear regression formulae for GC and dS are shown.CC BY · PubMed Central
Figure 5 Evolutionary dynamics of KRTAP genes. A comparison of the evolutionary dynamics as evaluated by Pearson correlation coefficient (r) of gene numbers of each subfamily between species is shown. A) The coefficient value for the high cysteine KRTAP and high glycine/tyrosine genes is shown with standard errors of the estimates. The correlation coefficient of the high cysteine genes is significantly higher than for the high glycine/tyrosine genes. B) A linear regression of the coefficients between high cysteine KRTAP and high glycine/tyrosine KRTAP genes. The two groups of coefficient values are positively correlated at the 1% level.
Figure 5 Evolutionary dynamics of KRTAP genes. A comparison of the evolutionary dynamics as evaluated by Pearson correlation coefficient (r) of gene numbers of each subfamily between species is shown. A) The coefficient value for the high cysteine KRTAP and high glycine/tyrosine genes is shown with standard errors of the estimates. The correlation coefficient of the high cysteine genes is significantly higher than for the high glycine/tyrosine genes. B) A linear regression of the coefficients between high cysteine KRTAP and high glycine/tyrosine KRTAP genes. The two groups of coefficient values are positively correlated at the 1% level.CC BY · PubMed Central

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Metadata

Authors
Wu, D.-D., Irwin, D. M., & Zhang, Y.-P.
Affiliations
  • Kunming Institute of Zoology (CN)
  • University of Toronto (CA)
Corresponding author
Zhang, Ya-Ping
ORCID
Venue
BMC Evolutionary Biology
Publisher
Springer Science and Business Media LLC
Published
2008-08-23
Volume
8
Issue
1
Pages
241-241
ISSN
1471-2148 (ISSN-L)
DOI
10.1186/1471-2148-8-241
PMC
PMC2528016
OpenAlex
W2059503064
Cited by
121
References
69
Citations by year
2026: 3 · 2025: 6 · 2024: 9 · 2023: 8 · 2022: 12 · 2021: 6 · 2020: 12 · 2019: 3 · 2018: 12 · 2017: 3 · 2016: 7 · 2015: 5 · 2014: 7 · 2013: 5 · 2012: 5
FWCI
2.63
Type
journal article
Language
en
Update notices
erratum (2009-08-25)
Open access
Licence
cc-by
Locations
  • BMC Evolutionary Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • TSpace (University of Toronto) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Deutsches Krebsforschungszentrum
  • National Natural Science Foundation of China (30430110, 973 Program, 30621092, 2007CB411600)
  • National Key Research and Development Program of China (2007CB411600)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
Keywords
keratin-associated proteins, hair shaft structure, rodents, concerted evolution, gene conversion, positive selection, GC content
MeSH terms
Amino Acid Sequence, Animals, Base Composition, Gene Conversion, Multigene Family, Hair, Humans, Keratins, Mammals, Phylogeny, Pseudogenes, Recombination, Genetic, Species Specificity, Genome, Human, Evolution, Molecular, Gene Duplication

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