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Article ; Online: Genetic Diversity on the Sex Chromosomes.

Wilson Sayres, Melissa A

2018 Volume 10, Issue 4, Page(s) 1064–1078

Abstract: Levels and patterns of genetic diversity can provide insights into a population's history. In species with sex chromosomes, differences between genomic regions with unique inheritance patterns can be used to distinguish between different sets of possible ...

Abstract	Levels and patterns of genetic diversity can provide insights into a population's history. In species with sex chromosomes, differences between genomic regions with unique inheritance patterns can be used to distinguish between different sets of possible demographic and selective events. This review introduces the differences in population history for sex chromosomes and autosomes, provides the expectations for genetic diversity across the genome under different evolutionary scenarios, and gives an introductory description for how deviations in these expectations are calculated and can be interpreted. Predominantly, diversity on the sex chromosomes has been used to explore and address three research areas: 1) Mating patterns and sex-biased variance in reproductive success, 2) signatures of selection, and 3) evidence for modes of speciation and introgression. After introducing the theory, this review catalogs recent studies of genetic diversity on the sex chromosomes across species within the major research areas that sex chromosomes are typically applied to, arguing that there are broad similarities not only between male-heterogametic (XX/XY) and female-heterogametic (ZZ/ZW) sex determination systems but also any mating system with reduced recombination in a sex-determining region. Further, general patterns of reduced diversity in nonrecombining regions are shared across plants and animals. There are unique patterns across populations with vastly different patterns of mating and speciation, but these do not tend to cluster by taxa or sex determination system.
MeSH term(s)	Animals ; Chromosomes, Human, X/genetics ; Chromosomes, Human, Y/genetics ; Female ; Genes, sry/genetics ; Genetic Variation ; Humans ; Male ; Recombination, Genetic/genetics ; Selection, Genetic/genetics ; Sex Chromosomes/genetics ; Sex Determination Processes/genetics
Language	English
Publishing date	2018-04-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2495328-3
ISSN	1759-6653 ; 1759-6653
ISSN (online)	1759-6653
ISSN	1759-6653
DOI	10.1093/gbe/evy039
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Article ; Online: The synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells.

Olney, Kimberly C / Nyer, David B / Vargas, Daniel A / Wilson Sayres, Melissa A / Haynes, Karmella A

BMC systems biology

2018 Volume 12, Issue 1, Page(s) 83

Abstract: Background: Mounting evidence from genome-wide studies of cancer shows that chromatin-mediated epigenetic silencing at large cohorts of genes is strongly linked to a poor prognosis. This mechanism is thought to prevent cell differentiation and enable ... ...

Abstract	Background: Mounting evidence from genome-wide studies of cancer shows that chromatin-mediated epigenetic silencing at large cohorts of genes is strongly linked to a poor prognosis. This mechanism is thought to prevent cell differentiation and enable evasion of the immune system. Drugging the cancer epigenome with small molecule inhibitors to release silenced genes from the repressed state has emerged as a powerful approach for cancer research and drug development. Targets of these inhibitors include chromatin-modifying enzymes that can acquire drug-resistant mutations. In order to directly target a generally conserved feature, elevated trimethyl-lysine 27 on histone H3 (H3K27me3), we developed the Polycomb-based Transcription Factor (PcTF), a fusion activator that targets methyl-histone marks via its N-terminal H3K27me3-binding motif, and co-regulates sets of silenced genes. Results: Here, we report transcriptome profiling analyses of PcTF-treated breast cancer model cell lines. We identified a set of 19 PcTF-upregulated genes, or PUGs, that were consistent across three distinct breast cancer cell lines. These genes are associated with the interferon response pathway. Conclusions: Our results demonstrate for the first time a chromatin-mediated interferon-related transcriptional response driven by an engineered fusion protein that physically links repressive histone marks with active transcription.
MeSH term(s)	Breast Neoplasms/pathology ; Genetic Loci/genetics ; Histones/metabolism ; Humans ; Interferons/genetics ; MCF-7 Cells ; Polycomb-Group Proteins/metabolism ; Transcriptional Activation
Chemical Substances	Histones ; Polycomb-Group Proteins ; Interferons (9008-11-1)
Language	English
Publishing date	2018-09-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1752-0509
ISSN (online)	1752-0509
DOI	10.1186/s12918-018-0608-4
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Article ; Online ; Research data: (with research data) Genetic Mapping and Phylogenetic Analysis Reveal Intraspecific Variation in Sex Chromosomes of the Virginian Strawberry.

Wei, Na / Govindarajulu, Rajanikanth / Tennessen, Jacob A / Liston, Aaron / Ashman, Tia-Lynn / Sayres, Melissa Wilson

The Journal of heredity

2017 Volume 108, Issue 7, Page(s) 731–739

Abstract: With their extraordinary diversity in sexual systems, flowering plants offer unparalleled opportunities to understand sex determination and to reveal generalities in the evolution of sex chromosomes. Comparative genetic mapping of related taxa with good ... ...

Abstract	With their extraordinary diversity in sexual systems, flowering plants offer unparalleled opportunities to understand sex determination and to reveal generalities in the evolution of sex chromosomes. Comparative genetic mapping of related taxa with good phylogenetic resolution can delineate the extent of sex chromosome diversity within plant groups, and lead the way to understanding the evolutionary drivers of such diversity. The North American octoploid wild strawberries provide such an opportunity. We performed linkage mapping using targeted sequence capture for the subdioecious western Fragaria virginiana ssp. platypetala and compared the location of its sex-determining region (SDR) to those of 2 other (sub)dioecious species, the eastern subspecies, F. virginiana ssp. virginiana (whose SDR is at 0-5.5 Mb on chromosome VI of the B2 subgenome), and the sister species F. chiloensis (whose SDR is at 37 Mb on chromosome VI of the Av subgenome). Male sterility was dominant in F. virginiana ssp. platypetala and mapped to a chromosome also in homeologous group VI. Likewise, one major quantitative trait locus (QTL) for female fertility overlapped the male sterility region. However, the SDR mapped to yet another subgenome (B1), and to a different location (13 Mb), but similar to the location inferred in one population of the naturally occurring hybrid between F. chiloensis and F. virginiana (F. ×ananassa ssp. cuneifolia). Phylogenetic analysis of chromosomes across the octoploid taxa showed consistent subgenomic composition reflecting shared evolutionary history but also reinforced within-species variation in the SDR-carrying chromosome, suggesting either repeated evolution, or recent turnovers in SDR.
Language	English
Publishing date	2017-10-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	3044-2
ISSN	1465-7333 ; 0022-1503 ; 0022-1503
ISSN (online)	1465-7333
ISSN	0022-1503
DOI	10.1093/jhered/esx077
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Article ; Online: Variable Autosomal and X Divergence Near and Far from Genes Affects Estimates of Male Mutation Bias in Great Apes.

Narang, Pooja / Wilson Sayres, Melissa A

Genome biology and evolution

2016 Volume 8, Issue 11, Page(s) 3393–3405

Abstract: Male mutation bias, when more mutations are passed on via the male germline than via the female germline, is observed across mammals. One common way to infer the magnitude of male mutation bias, α, is to compare levels of neutral sequence divergence ... ...

Abstract	Male mutation bias, when more mutations are passed on via the male germline than via the female germline, is observed across mammals. One common way to infer the magnitude of male mutation bias, α, is to compare levels of neutral sequence divergence between genomic regions that spend different amounts of time in the male and female germline. For great apes, including human, we show that estimates of divergence are reduced in putatively unconstrained regions near genes relative to unconstrained regions far from genes. Divergence increases with increasing distance from genes on both the X chromosome and autosomes, but increases faster on the X chromosome than autosomes. As a result, ratios of X/A divergence increase with increasing distance from genes and corresponding estimates of male mutation bias are significantly higher in intergenic regions near genes versus far from genes. Future studies in other species will need to carefully consider the effect that genomic location will have on estimates of male mutation bias.
MeSH term(s)	Animals ; Bias ; Female ; Hominidae/genetics ; Humans ; Male ; Mutation Rate ; Oocytes/metabolism ; Selection, Genetic ; Spermatozoa/metabolism ; X Chromosome/genetics ; X Chromosome Inactivation
Language	English
Publishing date	2016-12-31
Publishing country	England
Document type	Journal Article
ISSN	1759-6653
ISSN (online)	1759-6653
DOI	10.1093/gbe/evw232
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Article ; Online: Genomic signatures of sex-biased demography: progress and prospects.

Webster, Timothy H / Wilson Sayres, Melissa A

Current opinion in genetics & development

2016 Volume 41, Page(s) 62–71

Abstract: Sex-biased demographic events have played a crucial role in shaping human history. Many of these processes affect genetic variation and can therefore leave detectable signatures in the genome because autosomal, X-linked, Y-linked, and mitochondrial DNA ... ...

Abstract	Sex-biased demographic events have played a crucial role in shaping human history. Many of these processes affect genetic variation and can therefore leave detectable signatures in the genome because autosomal, X-linked, Y-linked, and mitochondrial DNA inheritance differ between sexes. Here, we discuss how sex-biased processes shape patterns of genetic diversity across the genome, review recent genomic evidence for sex-biased demography in modern human populations, and suggest directions for future research.
Language	English
Publishing date	2016-12
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	1077312-5
ISSN	1879-0380 ; 0959-437X
ISSN (online)	1879-0380
ISSN	0959-437X
DOI	10.1016/j.gde.2016.08.002
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Article ; Online: Fruitful analysis of sex chromosomes reveals X-treme genetic diversity.

Taravella, Angela M / Sayres, Melissa A Wilson

Genome biology

2016 Volume 17, Issue 1, Page(s) 244

Abstract: A new study on sex chromosome evolution in papaya helps to illuminate sex chromosome biology, including deviations from expected trajectories.Please see related Research article: https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1095-9. ...

Abstract	A new study on sex chromosome evolution in papaya helps to illuminate sex chromosome biology, including deviations from expected trajectories.Please see related Research article: https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1095-9.
MeSH term(s)	Carica/genetics ; Carica/growth & development ; Chromosomes, Plant/genetics ; Evolution, Molecular ; Genetic Variation ; Sex Chromosomes/genetics
Language	English
Publishing date	2016-11-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2040529-7
ISSN	1474-760X ; 1465-6914 ; 1465-6906
ISSN (online)	1474-760X ; 1465-6914
ISSN	1465-6906
DOI	10.1186/s13059-016-1115-9
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Article ; Online: Genetic Diversity on the Human X Chromosome Does Not Support a Strict Pseudoautosomal Boundary.

Cotter, Daniel J / Brotman, Sarah M / Wilson Sayres, Melissa A

Genetics

2016 Volume 203, Issue 1, Page(s) 485–492

Abstract: Unlike the autosomes, recombination between the X chromosome and the Y chromosome is often thought to be constrained to two small pseudoautosomal regions (PARs) at the tips of each sex chromosome. PAR1 spans the first 2.7 Mb of the proximal arm of the ... ...

Abstract	Unlike the autosomes, recombination between the X chromosome and the Y chromosome is often thought to be constrained to two small pseudoautosomal regions (PARs) at the tips of each sex chromosome. PAR1 spans the first 2.7 Mb of the proximal arm of the human sex chromosomes, whereas the much smaller PAR2 encompasses the distal 320 kb of the long arm of each sex chromosome. In addition to PAR1 and PAR2, there is a human-specific X-transposed region that was duplicated from the X to the Y chromosome. The X-transposed region is often not excluded from X-specific analyses, unlike the PARs, because it is not thought to routinely recombine. Genetic diversity is expected to be higher in recombining regions than in nonrecombining regions because recombination reduces the effect of linked selection. In this study, we investigated patterns of genetic diversity in noncoding regions across the entire X chromosome of a global sample of 26 unrelated genetic females. We found that genetic diversity in PAR1 is significantly greater than in the nonrecombining regions (nonPARs). However, rather than an abrupt drop in diversity at the pseudoautosomal boundary, there is a gradual reduction in diversity from the recombining through the nonrecombining regions, suggesting that recombination between the human sex chromosomes spans across the currently defined pseudoautosomal boundary. A consequence of recombination spanning this boundary potentially includes increasing the rate of sex-linked disorders (e.g., de la Chapelle) and sex chromosome aneuploidies. In contrast, diversity in PAR2 is not significantly elevated compared to the nonPARs, suggesting that recombination is not obligatory in PAR2. Finally, diversity in the X-transposed region is higher than in the surrounding nonPARs, providing evidence that recombination may occur with some frequency between the X and Y chromosomes in the X-transposed region.
MeSH term(s)	Chromosomes, Human, X/genetics ; Evolution, Molecular ; Female ; Humans ; Polymorphism, Genetic ; Pseudoautosomal Regions/genetics ; Recombination, Genetic
Language	English
Publishing date	2016-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2167-2
ISSN	1943-2631 ; 0016-6731
ISSN (online)	1943-2631
ISSN	0016-6731
DOI	10.1534/genetics.114.172692
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Article ; Online: Natural selection reduced diversity on human y chromosomes.

Wilson Sayres, Melissa A / Lohmueller, Kirk E / Nielsen, Rasmus

PLoS genetics

2014 Volume 10, Issue 1, Page(s) e1004064

Abstract: The human Y chromosome exhibits surprisingly low levels of genetic diversity. This could result from neutral processes if the effective population size of males is reduced relative to females due to a higher variance in the number of offspring from males ...

Abstract	The human Y chromosome exhibits surprisingly low levels of genetic diversity. This could result from neutral processes if the effective population size of males is reduced relative to females due to a higher variance in the number of offspring from males than from females. Alternatively, selection acting on new mutations, and affecting linked neutral sites, could reduce variability on the Y chromosome. Here, using genome-wide analyses of X, Y, autosomal and mitochondrial DNA, in combination with extensive population genetic simulations, we show that low observed Y chromosome variability is not consistent with a purely neutral model. Instead, we show that models of purifying selection are consistent with observed Y diversity. Further, the number of sites estimated to be under purifying selection greatly exceeds the number of Y-linked coding sites, suggesting the importance of the highly repetitive ampliconic regions. While we show that purifying selection removing deleterious mutations can explain the low diversity on the Y chromosome, we cannot exclude the possibility that positive selection acting on beneficial mutations could have also reduced diversity in linked neutral regions, and may have contributed to lowering human Y chromosome diversity. Because the functional significance of the ampliconic regions is poorly understood, our findings should motivate future research in this area.
MeSH term(s)	Chromosomes, Human, Y/genetics ; Computer Simulation ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; Female ; Genetic Drift ; Genetic Variation ; Genetics, Population ; Genome, Human ; Humans ; Male ; Mutation ; Open Reading Frames/genetics ; Selection, Genetic/genetics
Chemical Substances	DNA, Mitochondrial
Language	English
Publishing date	2014-01-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1004064
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Article ; Online: Fetal microchimerism and maternal health: a review and evolutionary analysis of cooperation and conflict beyond the womb.

Boddy, Amy M / Fortunato, Angelo / Wilson Sayres, Melissa / Aktipis, Athena

BioEssays : news and reviews in molecular, cellular and developmental biology

2015 Volume 37, Issue 10, Page(s) 1106–1118

Abstract: The presence of fetal cells has been associated with both positive and negative effects on maternal health. These paradoxical effects may be due to the fact that maternal and offspring fitness interests are aligned in certain domains and conflicting in ... ...

Abstract	The presence of fetal cells has been associated with both positive and negative effects on maternal health. These paradoxical effects may be due to the fact that maternal and offspring fitness interests are aligned in certain domains and conflicting in others, which may have led to the evolution of fetal microchimeric phenotypes that can manipulate maternal tissues. We use cooperation and conflict theory to generate testable predictions about domains in which fetal microchimerism may enhance maternal health and those in which it may be detrimental. This framework suggests that fetal cells may function both to contribute to maternal somatic maintenance (e.g. wound healing) and to manipulate maternal physiology to enhance resource transmission to offspring (e.g. enhancing milk production). In this review, we use an evolutionary framework to make testable predictions about the role of fetal microchimerism in lactation, thyroid function, autoimmune disease, cancer and maternal emotional, and psychological health. Also watch the Video Abstract.
MeSH term(s)	Animals ; Chimerism/embryology ; Female ; Fetus/cytology ; Fetus/metabolism ; Humans ; Maternal Health ; Maternal-Fetal Exchange/genetics ; Parturition/physiology ; Placenta/cytology ; Pregnancy
Language	English
Publishing date	2015-08-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	50140-2
ISSN	1521-1878 ; 0265-9247
ISSN (online)	1521-1878
ISSN	0265-9247
DOI	10.1002/bies.201500059
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Article ; Online: EvSex16: Evolutionary Genomics of Sex.

Olney, Kimberly C / Narang, Pooja / Taravella, Angela M / Webster, Timothy H / Wilson Sayres, Melissa A

The Journal of heredity

2017 Volume 108, Issue 7, Page(s) 707–708

MeSH term(s)	Biological Evolution ; Congresses as Topic ; Genetics, Population ; Genomics ; Sex Chromosomes/genetics
Language	English
Publishing date	2017-11-02
Publishing country	United States
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	3044-2
ISSN	1465-7333 ; 0022-1503
ISSN (online)	1465-7333
ISSN	0022-1503
DOI	10.1093/jhered/esx084
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