哺乳动物毛色形成机制与影响因素

哺乳动物拥有丰富多彩的毛色,对于多种多样的动物毛色,影响其形成的可能原因较多,遗传物质与环境的相互作用不可忽视。本文针对调控黑色素细胞形成及褐黑色素、真黑色素合成的相关基因,分析了哺乳动物毛色形成的可能机制,并对研究不同毛色动物的同种动物遗传差异的方法进行了讨论。     

绵羊黑色素合成相关基因的研究进展

毛色是一种可利用的遗传标记。在确定杂交组合、品种纯度和亲缘关系以及评价产品质量等方面均有一定的用途。哺乳动物毛色是由黑色素细胞产生的真黑素和褐黑素二者的分布和比例决定的。控制哺乳动物毛色色素的基因有很多,着重对黑色素合成相关基因酪氨酸酶基因(TYR)、黑素皮质激素受体1基因(MC1R)、鼠灰信号蛋白基因(Agouti)、酪氨酸酶相关蛋白1基因(TYRP1)的生物学功能及其遗传变异机制进行了综述。     

翼手目(蝙蝠)适应性进化分子机制的研究进展

作为哺乳动物第二大目的翼手目(Chiroptera;俗称蝙蝠)在飞行能力、回声定位与听觉系统、食性、冬眠、免疫防御等诸多方面表现出显著而独特的适应性进化,是研究生物对环境适应性进化分子机制的热点模型之一。文章综述了翼手目适应性进化分子机制的研究进展,特别是近年来在基因组水平上开展的相关研究,显示出更为复杂的分子进化模式和功能分化。随着越来越多的翼手目物种基因组数据的产生,将有望揭示新的进化机制,并为后续的功能实验奠定基础,促进人们对翼手目这一类群的认识和了解,同时也为系统认识动物适应性进化分子机制做出贡献。     

MicroRNA-411a-3p靶向钙/钙调素依赖蛋白激酶4调控羊驼黑色素细胞中的黑色素生成

羊驼是重要的毛用型经济动物,具有22种天然色。毛色由皮肤中黑色素细胞产生的黑色素颗粒的分布和转运所决定的。然而,羊驼色素形成或毛色形成的分子机制复杂,由多个基因、miRNA 和lncRNA调控。但是,miR-411a-3p 对羊驼色素形成起调控作用未见报道。为研究miR-411a-3p在黑色素产生过程中的调控作用,本文将构建的miR-411a-3p载体转染到羊驼黑色素细胞中,并对毛色基因的表达进行研究。经生物信息学预测,钙/钙调素依赖蛋白激酶4(calcium-calmodulin dependent protein kinase 4, CaMK4)可能是miR-411a-3p的靶基因之一。双荧光素酶报告基因结果显示,与对照组相比,双荧光报告酶活性下降（34.78 ± 16.09）%(P<0.01),其下降趋势明显,说明CaMK4可能是miR-411a-3p的靶基因之一。miR-411a-3p通过结合CaMK4的3′ untranslated region (3′-UTR)直接调控CaMK4的表达。在羊驼黑色素细胞中转染miR-411a-3p后,CaMK4、CDK5和TYRP1在转录水平的表达量与NC组相比具有显著下降趋势,其中TYRP1下降趋势尤为显著（53.66 ± 2.11）%（P<0.01）。Western印迹检测CaMK4、CDK5、TYRP1、p-CREB在蛋白质水平的表达与NC组相比下降趋势明显,尤其是CDK5和p-CREB基因下降极为显著,分别为（70.26 ± 4.84）%（P<0.01）和（70.11 ±9.05）%（P<0.01）。Masson-Fontana法检测黑色素颗粒,结果显示,miR-411a-3p抑制黑色素细胞产生黑色素颗粒。通过紫外分光度法检测真黑素（eumelanin,EM）和褐黑素（phenomelanin,PM）显示,EM和PM的含量均被下调。结果表明,miR-411a-3p靶向抑制CaMK4表达,从而改变CREB的表达以控制黑色素的产生,此研究结果对哺乳动物毛色形成机制有重要意义。     

MicroRNA-411a-3p靶向钙/钙调素依赖蛋白激酶4调控羊驼黑色素细胞中的黑色素生成

羊驼是重要的毛用型经济动物,具有22种天然色。毛色由皮肤中黑色素细胞产生的黑色素颗粒的分布和转运所决定的。然而,羊驼色素形成或毛色形成的分子机制复杂,由多个基因、miRNA 和lncRNA调控。但是,miR-411a-3p 对羊驼色素形成起调控作用未见报道。为研究miR-411a-3p在黑色素产生过程中的调控作用,本文将构建的miR-411a-3p载体转染到羊驼黑色素细胞中,并对毛色基因的表达进行研究。经生物信息学预测,钙/钙调素依赖蛋白激酶4(calcium-calmodulin dependent protein kinase 4, CaMK4)可能是miR-411a-3p的靶基因之一。双荧光素酶报告基因结果显示,与对照组相比,双荧光报告酶活性下降（34.78 ± 16.09）%(P<0.01),其下降趋势明显,说明CaMK4可能是miR-411a-3p的靶基因之一。miR-411a-3p通过结合CaMK4的3′ untranslated region (3′-UTR)直接调控CaMK4的表达。在羊驼黑色素细胞中转染miR-411a-3p后,CaMK4、CDK5和TYRP1在转录水平的表达量与NC组相比具有显著下降趋势,其中TYRP1下降趋势尤为显著（53.66 ± 2.11）%（P<0.01）。Western印迹检测CaMK4、CDK5、TYRP1、p-CREB在蛋白质水平的表达与NC组相比下降趋势明显,尤其是CDK5和p-CREB基因下降极为显著,分别为（70.26 ± 4.84）%（P<0.01）和（70.11 ±9.05）%（P<0.01）。Masson-Fontana法检测黑色素颗粒,结果显示,miR-411a-3p抑制黑色素细胞产生黑色素颗粒。通过紫外分光度法检测真黑素（eumelanin,EM）和褐黑素（phenomelanin,PM）显示,EM和PM的含量均被下调。结果表明,miR-411a-3p靶向抑制CaMK4表达,从而改变CREB的表达以控制黑色素的产生,此研究结果对哺乳动物毛色形成机制有重要意义。     

MicroRNA-411a-3p靶向钙/钙调素依赖蛋白激酶4调控羊驼黑色素细胞中的黑色素生成（英文）

羊驼是重要的毛用型经济动物,具有22种天然色。毛色由皮肤中黑色素细胞产生的黑色素颗粒的分布和转运所决定的。然而,羊驼色素形成或毛色形成的分子机制复杂,由多个基因、miRNA和lncRNA调控。但是,miR-411a-3p对羊驼色素形成起调控作用未见报道。为研究miR-411a-3p在黑色素产生过程中的调控作用,本文将构建的miR-411a-3p载体转染到羊驼黑色素细胞中,并对毛色基因的表达进行研究。经生物信息学预测,钙/钙调素依赖蛋白激酶4(calcium-calmodulin dependent protein kinase 4, CaMK4)可能是miR-411a-3p的靶基因之一。双荧光素酶报告基因结果显示,与对照组相比,双荧光报告酶活性下降(34.78±16.09)%(P0.01),其下降趋势明显,说明CaMK4可能是miR-411a-3p的靶基因之一。miR-411a-3p通过结合CaMK4的3′untranslated region (3′-UTR)直接调控CaMK4的表达。在羊驼黑色素细胞中转染miR-411a-3p后,CaMK4、CDK5和TYRP1在转录水平的表达量与NC组相比具有显著下降趋势,其中TYRP1下降趋势尤为显著(53.66±2.11)%(P0.01)。Western印迹检测CaMK4、CDK5、TYRP1、p-CREB在蛋白质水平的表达与NC组相比下降趋势明显,尤其是CDK5和p-CREB基因下降极为显著,分别为(70.26±4.84)%(P0.01)和(70.11±9.05)%(P0.01)。Masson-Fontana法检测黑色素颗粒,结果显示,miR-411a-3p抑制黑色素细胞产生黑色素颗粒。通过紫外分光度法检测真黑素(eumelanin,EM)和褐黑素(phenomelanin,PM)显示,EM和PM的含量均被下调。结果表明,miR-411a-3p靶向抑制CaMK4表达,从而改变CREB的表达以控制黑色素的产生,此研究结果对哺乳动物毛色形成机制有重要意义。     

马毛色遗传的分子基础与应用

毛色不仅是马品种和个体识别的重要依据,而且还可以作为某些疾病筛查的有力工具和手段。马的毛色主要由黑色素细胞产生的真黑素和褐黑素两种黑色素的分布及比例所决定,许多基因对黑色素的产生和分布的调控起着重要的作用,各基因相互间共同作用最终形成各种单毛色和复毛色,这些基因主要包括MC1R、ASIP、KIT、TYRP和EDNRB。另外STX17、MATP和PMEL17也在马毛色形成过程具有重要的作用,同时还发现个别毛色基因与黑色素瘤疾病有关。文章对近年来马主要毛色候选基因的作用机理、DNA序列多态性与毛色性状及黑色素瘤疾病的关系等研究进行了详细的阐述,为今后马匹育种工作和疾病防治提供重要理论依据。     

昆虫着色及体表黑色斑纹和斑点形成机制研究进展

昆虫在生长发育的过程中,会不断受到捕食者的攻击,为逃避被捕食在长期的适应进化中展现出各种适应性的形态特征,体色和斑纹的适应性变化是其中重要的防御策略。昆虫多样的着色模式常用于释放警告信号或者模仿宿主植物,避免被其他动物捕食并且加速逃避学习,而且在寻求伴侣、适应地理、调节体温和抵抗紫外线等方面发挥重要的生物功能,是昆虫学研究的热点之一。鳞翅目昆虫具有分布广、种类多的特点,大量的斑点和斑纹模式常见于鳞翅目昆虫中,其生物学功能比其他动物更明显。近年来研究发现色素色和结构色是昆虫主要的着色模式,眼色素、黑色素以及喋啶类色素是影响昆虫着色最重要的色素;而昆虫的寄主、环境因素、激素显著影响昆虫多样性着色模式的形成。利用定位克隆、经典遗传连锁图谱、RNA干涉、基因组编辑、高通量测序等技术分离鉴定出了多个调控鳞翅目昆虫着色的关键基因。研究表明, TH, DDC, yellow, laccase2, ebony, AA-NAT, tan和GTPCHI是昆虫色素合成信号通路中的关键基因,而多效性基因spz3, apt-like和wnt1以及20E诱导的转录因子E75A和spalt通过影响鳞翅目昆虫黑色素合成信号通路的活性从而调控黑色素的合成与沉积。本文对昆虫体色和斑纹多样性的形成和影响因素,昆虫着色类型及物质基础,以及黑色斑点和斑纹形成和调节机制方面的研究进展作了整理和总结,以期为今后着色基因的利用以及害虫防治提供理论参考。     

蚜虫体色多态性及生态进化功能

体色多态性在蚜虫中普遍存在,是探索生物适应环境机制及生态进化功能的一个优良范式。尽管蚜虫体色多态性被认知已经有两个多世纪,但其内在的机制仍然不甚明了。本文从蚜虫体色多态性的表现形式、体色的组成部分及色素种类、影响体色多态的重要因子、体色多态的生态功能及维持体色多态性的机制等方面综述有关研究进展,为进一步研究蚜虫体色分化的内在机理、体色多态的维持机制及体色多态的生态进化功能等提供方向和线索。     

黑色素羽毛装饰反映了鸟类的抗氧化和免疫能力吗?

鸟类信号系统研究认为,不同于类胡萝卜素,基于黑色素的羽色装饰不需要昂贵的生理代价。然而,羽毛色素细胞的黑色素沉积与抗氧化能力和免疫系统有很强的联系,而抗氧化能力和免疫系统在提高有机体适合度方面具有重要的功能。黑色素细胞的生长对氧化环境压力十分敏感;并且,黑色素本身似乎就具有抗氧化剂的功能。相应地,把抗氧化剂用于以黑色素为基础羽色发育,还是用于其它方面例如免疫调节和免疫刺激等,个体也许必须对此做出权衡。组织中的抗氧化功能大多与代谢活动有关,也就是和自由基的最高水平有关。此外,人们发现,在哺乳动物中调节黑色素沉积的激素,即α黑素细胞刺激素,在鸟类上皮组织的色素沉积中也具有同样的功能。这种进化保守的激素是免疫和炎症反应的一个重要介体。它下调前炎性细胞因子、免疫介导细胞因子和协同刺激分子,以及主要组织相容性复合体Ⅰ类分子在单核细胞的表达以及抗体的产生,而上调抑制因子白介素。黑色素在羽毛上的大量沉积,也可能反映出免疫系统在局部免疫应答的负调控能力。这些将黑色素沉积和抗氧化剂以及免疫功能联系起来的机制,表明基于黑色素的羽色信号具有一定的生理代价,这些对以往关于黑色素的优势作用的假说提出质疑     

Exclusion of melanocortin-1 receptor (mc1r) and agouti as candidates for dominant black in dogs

The domestic dog exhibits a variety of coat colors that encompass a wide range of variation among different breeds. Very little is known about the molecular biology of dog pigmentation; current understanding is based mostly on traditional breeding experiments, which in some cases have suggested genetic interactions that are different from those reported in other mammals. We have examined the molecular genetics of dominant black, a uniform coat color characteristic of black Labrador retrievers or Newfoundlands that has been proposed to be caused by either variation in the melanocortin-1 receptor gene (Mc1r) or by variation in the Agouti gene (A). We identified several coding polymorphisms within Mc1r and several simple sequence repeat polymorphisms closely linked to A, and examined their inheritance in a Labrador retriever x greyhound cross that segregates dominant black. No single Mc1r allele was found consistently in animals carrying dominant black, and neither Mc1r nor A cosegregated with dominant black. These results refine our understanding of mammalian coat color inheritance and suggest that dominant black coat color in dogs is caused by a gene not previously implicated in pigment type switching.     

Role of light in human skin color viariation.

The major source of color in human skin derives from the presence within the epidermis of specialized melanin-bearing organelles, the melanosomes. Tanning of human skin on exposure to ultraviolet light results from increased amounts of melanin within the epidermis. Melanosomes synthesized by melanocytes are acquired by keratinocytes and transported within them to the epidermal surface. In some cases, the melanosomes are catobolized en route. New information indicates that the multicellular epidermal melanin unit (melanocyte and associated pool of keratinocytes) rather than the melanocyte alone is the focal point for the control of melanin metabolism within mammalian epidermis. Gross human skin color derives from the visual impact of the summed melanin pigmentation of the many epidermal melanin units. In theory, constitutive skin color in man designates the genetically-determined levels of melanin pigmentation developed in the absence of exposure to solar radiation or other environmental influences; facultative skin color or "tan" characterizes the increases in melanin pigmentation above the constitutive level induced by ultraviolet light. The details of genetic regulation of pigment metabolism within the epidermal melanin units are being clarified. In some mammals at least, the function of epidermal melanin units is significantly influenced by hormones which may be regulated by radiations received through the eyes. Based on an evolutionary history of the human family which exceeds ten million years, it is proposed that melanin pigmentation may have played a number of roles in human adaptions to changing biologic and physical environments.     

Enzymatic control of pigmentation in mammals.

Visible pigmentation in mammals results from the synthesis and distribution of melanin in the skin, hair bulbs, and eyes. The melanins are produced in melanocytes and can be of two basic types: eumelanins, which are brown or black, and phaseomelanins, which are red or yellow. In mammals typically there are mixtures of both types. The most essential enzyme in this melanin biosynthetic pathway is tyrosinase and it is the only enzyme absolutely required for melanin production. However, recent studies have shown that mammalian melanogenesis is not regulated solely by tyrosinase at the enzymatic level, and have identified additional melanogenic factors that can modulate pigmentation in either a positive or negative fashion. In addition, other pigment-specific genes that are related to tyrosinase have been cloned which encode proteins that apparently work together at the catalytic level to specify the quantity and quality of the melanins synthesized. Future research should provide a greater understanding of the enzymatic interactions, processing, and tissue specificity that are important to pigmentation in mammals.     

黑素皮质激素受体1（MC1R）基因系统发育树与犬的毛色

犬的驯养迄今约有1万多年,由于不同环境和不同目的人工选择形成了犬品种间或品种内极丰富的毛色多样性,经证实,这些犬的很多毛色类型与MC1R相关 ,MC1R在一些物种中有同源基因 本文阐述了犬MC1R多态性研究进展,并选择其它9个有代表性的哺乳动物物种与犬MC1R同源基因进行了比较,以此建立系统发育树。结果显示,10个物种的MC1R基因的分子进化关系与物种的经典分类学地位基本相符。      

马毛色遗传机理研究进展

动物毛色是人类正向选择产生的表型之一,在遗传与进化过程中扮演着重要角色。其中马的毛色丰富多变,单从表型无法准确判别其属于哪种毛色,造成马品种登记时毛色性状记录不准确,因此研究马毛色形成机理在育种工作中具有重要意义。随着基因组学及测序技术的日益成熟,马毛色形成遗传机理的研究不断深入,并发现不同毛色性状与特定疾病之间的相关性。本文从遗传学的角度对马的毛色进行归类,对与其形成的相关基因、作用机理及应用等研究进展进行了综述,以期为马毛色形成机理的系统性研究和马匹选育提供借鉴和参考。     

Skin as a living coloring book: how epithelial cells create patterns of pigmentation

The pigmentation of mammalian skin and hair develops through the interaction of two basic cell types — pigment donors and recipients. The pigment donors are melanocytes, which produce and distribute melanin through specialized structures. The pigment recipients are epithelial cells, which acquire melanin and put it to use, collectively yielding the pigmentation visible to the eye. This review will focus on the pigment recipients, the historically less understood cell type. These end‐users of pigment are now known to exert a specialized control over the patterning of pigmentation, as they identify themselves as melanocyte targets, recruit pigment donors, and stimulate the transfer of melanin. As such, this review will discuss the evidence that the skin is like a coloring book: the pigment recipients create a ‘picture,’ a blueprint for pigmentation, which is colorless initially but outlines where pigment should be placed. Melanocytes then melanize the recipients and ‘color in’ the picture.     

miR-380调控羊驼黑色素细胞MAPK/ERK信号通路

miR-380是不同羊驼毛色中差异表达的基因之一,但是否与黑色素生成有关未见报道。为了丰富调控黑色素生成的机制,挖掘黑色素生成路径中所涉及到的更多新的基因并揭示miR 380在黑色素细胞中的功能,本实验通过生物信息学方法预测出MAPK信号通路的成员MAP3K6是miR-380的靶基因之一。在293T细胞中共转染miR-380和MAP3K6后,与对照组相比双荧光报告酶活性下降（28.92 ± 25.63）%(P<0.01) ,下降趋势明显,说明MAP3K6可能是miR-380的靶基因之一;在羊驼黑色素细胞中转染miR-380后,MAP3K6、MEK1、ERK1/2、CREB和MITF在转录水平的表达量与NC组相比具有显著下降趋势,其中CREB下降趋势尤为显著（64.20 ± 54.30）%（P<0.01）,Western印迹检测MAP3K6、p-MEK1、p-ERK1/2、CREB和MITF在蛋白质水平的表达与NC组相比下降趋势明显且p-MEK1和CREB基因下降极为显著,分别为（29.09 ± 10.68）%（P<0.001）和（47.12 ± 6.70）%（P<0.001）,抑制组则反之。通过 Masson-Fontana黑色素颗粒染色法检测miR-380抑制黑色素细胞产生黑色素颗粒,用紫外分光度法检测真黑素（eumelanin,EM）和褐黑素（pheomelanin,PM）,含量结果提示EM与PM含量分别下降为（38.63 ± 2.00）%（P<0.01）,（54.10 ± 5.73）%（P<0.001）且PM含量下降极为显著。综上所述miR-380通过靶向抑制MAP3K6等基因的表达,从而对MAPK/ERK信号通路起调控作用,最终影响黑色素生成生物学功能,此研究对哺乳动物毛色形成机制和防止皮肤受紫外辐射有重要意义。     

Variation of the melanocortin 1 receptor gene in the macaques

Melanocortin 1 receptor (MC1R), a G-coupled seven-transmembrane receptor protein, plays a key role in the regulation of melanin synthesis in mammals. Sequence variation of the MC1R gene (MC1R) has been associated with pigmentation phenotypes in humans and in several animal species. The macaques (genus Macaca) are known to show a marked inter-specific variation in coat color although the causative genetic variation remains unclear. We investigated nucleotide sequences of the MC1R in 67 individuals of 18 macaque species with different coat color phenotypes including black and agouti. Twenty-eight amino acid replacements were identified in the macaques, but none of these amino acid replacements could explain the black coat color of Macaca silenus and the Sulawesi macaque species. Our molecular evolutionary analysis has revealed that nonsynonymous substitution/synonymous substitution (dN/dS) ratio of the MC1R has not been uniform in the macaque groups and, moreover, their coat color and dN/dS ratio were not related. These results suggest that the MC1R is unlikely to be responsible for the coat color variation of the macaques and functions of MC1R other than pigmentation might be associated with the different selective pressures on the MC1R in macaques.     

Human pigmentation genes: identification, structure and consequences of polymorphic variation

The synthesis of the visible pigment melanin by the melanocyte cell is the basis of the human pigmentary system, those genes directing the formation, transport and distribution of the specialised melanosome organelle in which melanin accumulates can legitimately be called pigmentation genes. The genes involved in this process have been identified through comparative genomic studies of mouse coat colour mutations and by the molecular characterisation of human hypopigmentary genetic diseases such as OCA1 and OCA2. The melanocyte responds to the peptide hormones alpha-MSH or ACTH through the MC1R G-protein coupled receptor to stimulate melanin production through induced maturation or switching of melanin type. The pheomelanosome, containing the key enzyme of the pathway tyrosinase, produces light red/yellowish melanin, whereas the eumelanosome produces darker melanins via induction of additional TYRP1, TYRP2, SILV enzymes, and the P-protein. Intramelanosomal pH governed by the P-protein may act as a critical determinant of tyrosinase enzyme activity to control the initial step in melanin synthesis or TYRP complex formation to facilitate melanogenesis and melanosomal maturation. The search for genetic variation in these candidate human pigmentation genes in various human populations has revealed high levels of polymorphism in the MC1R locus, with over 30 variant alleles so far identified. Functional correlation of MC1R alleles with skin and hair colour provides evidence that this receptor molecule is a principle component underlying normal human pigment variation.