Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant
نویسندگان
چکیده
An adaptive variant of the human Ectodysplasin receptor, EDARV370A, is one of the strongest candidates of recent positive selection from genome-wide scans. We have modeled EDAR370A in mice and characterized its phenotype and evolutionary origins in humans. Our computational analysis suggests the allele arose in central China approximately 30,000 years ago. Although EDAR370A has been associated with increased scalp hair thickness and changed tooth morphology in humans, its direct biological significance and potential adaptive role remain unclear. We generated a knockin mouse model and find that, as in humans, hair thickness is increased in EDAR370A mice. We identify new biological targets affected by the mutation, including mammary and eccrine glands. Building on these results, we find that EDAR370A is associated with an increased number of active eccrine glands in the Han Chinese. This interdisciplinary approach yields unique insight into the generation of adaptive variation among modern humans.
منابع مشابه
P-121: Cloning and Expression of The Inosine Triphosphate Pyrophosphatase Gene Variant II in E.coli
Background Environmental and cellular inappropriate conditions can cause damages to cells nucleotide poll. Deamination and oxidation damages interfere with cell�s vital reactions. Inosine triphosphate pyrophosphatase (ITPA), an evolutionary conserved enzyme, plays a critical role in elimination of non-canonical bases. In human genome, the ITPA gene is located on chromosome 20 short arm and tran...
متن کاملP-157: Polymorphic Core Promoter GA-repeats Alter Gene Expression of The Early Embryonic Developmental Genes
Background: We examine the GA-repeat core promoters of MECOM and GABRA3 in human embryonic kidney-293 cell line and show that those GA-repeats have promoter activity,and those different alleles of the repeats can significantly alter gene expression.We propose a novel role for GA-repeat core promoters to regulate gene expression in the genes involved in development and evolution. Materials and M...
متن کاملP-215: Discovery of A Novel APA Variant of A Human Potential Gene Based on Expressed Sequenced Tags Analysis
Background: Expressed sequence tags (ESTs) are sequences of cDNA fragments prepared from different tissue sources. There are over one million of these sequences in the publicly available database, and these sequences are believed to represent more than half of all human genes. The ESTs belong to different cDNA libraries, was prepared from one particular cell type, organ, or tumor. Therefore, th...
متن کاملThe activation level of the TNF family receptor, Edar, determines cusp number and tooth number during tooth development.
Mutations in members of the ectodysplasin (TNF-related) signalling pathway, EDA, EDAR, and EDARADD in mice and humans produce an ectodermal dysplasia phenotype that includes missing teeth and smaller teeth with reduced cusps. Using the keratin 14 promoter to target expression of an activated form of Edar in transgenic mice, we show that expression of this transgene is able to rescue the tooth p...
متن کاملCloning, Expression and Characterization of Recombinant Human Fc Receptor Like 1, 2 and 4 Molecules
Background: The Fc receptor like (FCRL) molecules belong to the immunoglobulin (Ig) superfamily with potentially immunoregulatory <span style="font-va...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Cell
دوره 152 شماره
صفحات -
تاریخ انتشار 2013