Open Access
Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators
Jennifer F. Hughes,Helen Skaletsky,Laura G. Brown,Tatyana Pyntikova,Ting-Jan Cho,Natalia Koutseva,Sara Zaghlul,Tina Graves,Susie Rock,Colin Kremitzki,Robert S. Fulton,Shannon Dugan,Yan Ding,Donna Morton,Ziad Khan,Lora Lewis,Christian J. Buhay,Qiaoyan Wang,Jennifer Watt,Michael Holder,Sandy Lee,Lynne V. Nazareth,Jessica Alföldi,Steve Rozen,Donna M. Muzny,Wesley C. Warren,Richard A. Gibbs,Rick K. Wilson,Daniel W. Bellott,David C. Page +29 more
TLDR
This article reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes, and concluded that the gene content of Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X-Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability.Abstract:
The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes. Our findings indicate that survival was nonrandom, and in two cases, convergent across placental and marsupial mammals. We conclude that the gene content of the Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X–Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability. We propose that beyond its roles in testis determination and spermatogenesis, the Y chromosome is essential for male viability, and has unappreciated roles in Turner’s syndrome and in phenotypic differences between the sexes in health and disease.read more
Citations
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Landscape of X chromosome inactivation across human tissues
Taru Tukiainen,Taru Tukiainen,Alexandra-Chloé Villani,Alexandra-Chloé Villani,Angela Yen,Angela Yen,Manuel A. Rivas,Manuel A. Rivas,Manuel A. Rivas,Jamie L. Marshall,Jamie L. Marshall,Rahul Satija,Rahul Satija,Matthew Aguirre,Matthew Aguirre,Laura D. Gauthier,Laura D. Gauthier,Mark Fleharty,Andrew Kirby,Andrew Kirby,Beryl B. Cummings,Beryl B. Cummings,Stephane E. Castel,Konrad J. Karczewski,Konrad J. Karczewski,François Aguet,Andrea Byrnes,Andrea Byrnes,Tuuli Lappalainen,Aviv Regev,Aviv Regev,Kristin G. Ardlie,Nir Hacohen,Nir Hacohen,Daniel G. MacArthur,Daniel G. MacArthur +35 more
TL;DR: It is shown that incomplete XCI affects at least 23% of X-chromosomal genes, identified seven genes that escape XCI with support from multiple lines of evidence and demonstrated that escape from XCI results in sex biases in gene expression, establishing incomplete X CI as a mechanism that is likely to introduce phenotypic diversity.
Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues
TL;DR: For example, this paper found that while tissue-specific gene expression programs are largely conserved, alternative splicing is well conserved in only a subset of tissues and is frequently lineage-specific.
Journal ArticleDOI
Evolution by gene loss
Ricard Albalat,Cristian Cañestro +1 more
TL;DR: These questions are addressed, and insights are discussed from genomic studies of gene loss in populations and their relevance in evolutionary biology and biomedicine.
Journal ArticleDOI
Hypertension Renin–Angiotensin–Aldosterone System Alterations
TL;DR: Animal studies support the existence of protective aminopeptidase A-Ang III-Ang II type 2 receptor and ACE2-Ang-(1 to 7)-Mas receptor arms, paving the way for multiple new treatment options for resistant hypertension.
Journal ArticleDOI
Functional coherence of the human y chromosome
Bruce T. Lahn,David C. Page +1 more
TL;DR: A systematic search of the nonrecombining region of the human Y chromosome (NRY) identified 12 novel genes or families, 10 with full-length complementary DNA sequences, which may account for infertility among men with Y deletions.
References
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Journal ArticleDOI
MUSCLE: multiple sequence alignment with high accuracy and high throughput
TL;DR: MUSCLE is a new computer program for creating multiple alignments of protein sequences that includes fast distance estimation using kmer counting, progressive alignment using a new profile function the authors call the log-expectation score, and refinement using tree-dependent restricted partitioning.
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PAML: a program package for phylogenetic analysis by maximum likelihood
TL;DR: The strength of PAML, in comparison with other phylogenetic packages currently available, is its implementation of a variety of evolutionary models, which include several models of variable evolutionary rates among sites, models for combined analyses of multiple gene sequence data and models for amino acid sequences.
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A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif
Andrew H. Sinclair,Berta P,Berta P,M. S. Palmer,Hawkins,B. Griffiths,Smith Mj,Foster Jw,Foster Jw,A.-M. Frischauf,Robin Lovell-Badge,Peter N. Goodfellow +11 more
TL;DR: A search of a 35-kilobase region of the human Y chromosome necessary for male sex determination has resulted in the identification of a new gene, termed SRY (for sex-determining region Y) and proposed to be a candidate for the elusive testis-d determining gene, TDF.
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PANTHER: a library of protein families and subfamilies indexed by function.
Paul Thomas,Michael J. Campbell,Anish Kejariwal,Huaiyu Mi,Brian Karlak,Robin Daverman,Karen Diemer,Anushya Muruganujan,Apurva Narechania +8 more
TL;DR: The PANTHER/X ontology is used to give a high-level representation of gene function across the human and mouse genomes, and the family HMMs are used to rank missense single nucleotide polymorphisms (SNPs) according to their likelihood of affecting protein function.