遗传变异
章节大纲
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Jumping for Joy!
::跳跃乔伊!The people in this picture illustrate some of the great phenotypic variation displayed in modern Homo sapiens . The lighter-skinned men in the photo are Euro-American tourists in Kenya (East Africa). The other men are native Kenyans who belong to a tribal group named the Maasai. The men come from on different continents on opposite sides of the globe. Their populations have different histories, environments, and cultures. Besides differences in skin color, the men have different hair and eye colors, facial features, and body builds. Based on such obvious physical differences, you might think that our is characterized by a high degree of . In fact, there is much less genetic variation in the human species than there is in many other mammalian species, including our closest relatives — the chimpanzees.
::照片中的人展示了现代智人中展示的一些巨大的口腔差异。照片中较轻的皮肤男子是肯尼亚(东非)的欧洲-美国游客。其他男人是肯尼亚本地人,属于一个名为马赛的部落群体。这些人来自全球对面的不同大陆,其人口有着不同的历史、环境和文化。除了肤色差异外,男人有不同的头发和眼睛颜色、面部特征和身体。根据这些明显的身体差异,你可能会认为我们的特征是高度的。事实上,人类物种的遗传差异远小于许多其他哺乳动物物种,包括我们的近亲黑猩猩。Overview of Human Genetic Variation
::人类遗传变化概览No two human individuals are genetically identical unless they are monozygotic (identical) twins. Between any two people, differs, on average, at about one in one thousand nucleotide base pairs. We each have a total of about three billion base pairs, so any two people differ by an average of about three million base pairs. That may sound like a lot, but it's only 0.1 percent of our total genetic makeup. This means that two people chosen at random are likely to be 99.9 percent identical genetically, no matter where in the world they come from.
::没有两个人类在基因上是相同的,除非它们是单一的双胞胎。在任何一个人之间,平均相差大约千分之一。我们各有大约30亿对基对,因此任何两个人平均相差大约300万对基对。这听起来像很多,但只占我们基因构成总数的0.1%。这意味着随机选择的两个人在基因上可能达到99.9%,不管他们来自哪个世界。At an individual level, most human genetic variation is not very important biologically, because it has no apparent adaptive significance. It neither enhances nor detracts from individual fitness . Only a small percentage of DNA variations actually occur in coding regions of DNA — which are sequences that are translated into — or in regulatory regions, which are sequences that control . Differences that occur in other regions of DNA have no impact on phenotype . Even variations in coding regions of DNA may or may not affect phenotype. Some DNA variations may alter the amino acid sequence of a protein, but not affect how the protein functions. Other DNA variations do not even change the amino acid sequence of the encoded protein.
::在个人层面,大多数人类基因变异在生物学上并不非常重要,因为它没有明显的适应意义,既不增进也不减损个人健康,只有一小部分DNA变异实际上发生在DNA的编码区域——这些序列被转化成——或管制区域,它们是控制基因的序列。在DNA的其他区域出现的差异对基因型没有影响,甚至DNA编码区域的变异也可能不会影响基因型。一些DNA变异可能改变蛋白的氨酸序列,但不会影响蛋白的功能。其他DNA变异甚至不会改变编码蛋白的氨酸序列。At a population level, genetic variation is crucial if evolution is to occur. Genetically-based differences in fitness among individuals are the key to evolution by . Without genetic variation within populations, there can be no differential fitness by genotype , and natural selection cannot occur.
::在人口层面,基因变异是进化的关键。 基因变异是进化的关键。 人与人之间基于基因的体格差异是进化的关键。 没有人口内部的基因变异,就不可能有基因型的变异,自然选择也不可能发生。Patterns of Human Genetic Variation
::人类基因变异模式Data comparing DNA sequences from around the world show that only about ten percent of our total genetic variation occurs between people from different continents, like the American tourists and African Maasai pictured above. The other 90 percent of genetic variation occurs between people within continental populations, such as between North Americans or between Africans. Within any , many genes have two or more normal that contribute to genetic differences among individuals. The case in which a gene has two or more alleles in a population at frequencies greater than one percent is called a polymorphism. A s ingle nucleotide polymorphism (SNP) involves variation in just one nucleotide in a DNA sequence. SNPs account for most of our genetic differences. Other types of variations (such as deletions and insertions of nucleotides in DNA sequences) account for a much smaller proportion of our overall genetic variation.
::比较世界各地DNA序列的数据显示,我们全部基因变异中,只有大约10%发生在来自不同大陆的人之间,如上面所描绘的美国游客和非洲马萨伊人。其他90%的基因变异发生在大陆人口之间,如北美人之间或非洲人之间。在任何一种基因中,许多基因有两种或两种以上正常,造成个人之间的基因变异。在一个频率大于1%的人口中,基因有两个或两个以上的异象,这种情况被称为多元形态。单核酸多形态(SNP)只涉及一个DNA序列的核核素变异。SNP占我们基因变异的大部分。其他种类的变异(如删除和插入核素在DNA序列中)占我们整体基因变异的较小比例。Different populations may have different allele frequencies for polymorphic genes. However, the distribution of allele frequencies in different populations around the world tends not to be discrete or distinct. Instead, the pattern is more often one of gradual geographic variations, or clines, in allele frequencies. You can see an example of a clinal distribution of allele frequencies in the map . Clinal distributions like this may be a reflection of natural selection pressures varying continuously over geographic space, or they may reflect a combination of and of neutral alleles.
::不同的人群可能具有不同的多形态基因异端频率。 但是,世界各地不同人群中异端频率的分布往往不是离散的或不同的。 相反,这种模式更经常地是异端频率的渐进地理变化,或者说直线。您可以看到地图中全端频率的临床分布的例子。像这样的直端分布可能反映了地理空间之间不断变化的自然选择压力,或者它们可能反映中度异端的组合和中性异端的组合。This map shows the Old World clinal distribution of a single nucleotide polymorphism. The inset map focuses on the Indian subcontinent in South Asia. The red dots are locations where samples were collected. The numbers on the X-axis are allele frequencies.
::此地图显示一个单核酸多元形态的旧世界临床分布。 内置地图以南亚的印度次大陆为重点。 红色点是采集样本的地点。 X 轴上的数值是所有频率 。Although most genetic variation occurs within rather than between populations, certain alleles do seem to cluster in particular geographic areas. One example happens with the Duffy gene. Variations in this gene are the basis of the Duffy group, which is determined by the presence or absence of a red blood cell antigen , similar to the more familiar ABO blood group antigens. The genotype for no antigen for the Duffy blood group is far higher in African populations and in people who have African ancestry than it is in non-African people, as indicated in the following . Genes (such as the Duffy gene) may be useful as genetic markers to establish the ancestral populations of individuals.
::虽然大多数基因变异都发生在人口内部而不是人口之间,但某些异种似乎都集中在特定地理区域,Duffy基因就是一个例子,Duffy基因的变异是Duffy组的基础,该基因的变异是由红色血细胞抗原的存在或不存在所决定的,这类似于比较熟悉的ABO血族抗原,Duffy血族没有抗原的基因型在非洲人口和拥有非洲血统的人中远远高于非非洲人,如下文所示。基因(例如Duffy基因)可作为基因标记,用来确定个人的祖传人口。Population Frequencies for No Antigen in the Duffy Blood Group Population Percent of Population Lacking Duffy Antigen African
::非洲人非洲非洲人88-100 African American
::非裔美国人68 non-African American
::非非洲裔美国人<1 The reason for the different population frequencies for the Duffy antigen appears to be natural selection. People who lack the Duffy antigen are relatively resistant to malaria , which is one of the oldest and most devastating human diseases. Malaria has been a persistent and widespread disease in sub-Saharan Africa for tens of thousands of years. DNA analyses suggest that the allele associated with lack of the Duffy antigen evolved at least twice in Africa and was strongly selected for, causing it to increase in frequency . The Duffy gene is just one of many genes that have polymorphic alleles, because one of the alleles protects against malaria. In fact, a greater number of known genetic polymorphisms may be attributed to selection because of malaria than any other single selective agent.
::缺乏Duffy抗原的人相对抗疟疾,疟疾是人类最古老和最具破坏性的疾病之一;疟疾是撒哈拉以南非洲数万年来长期流行的疾病;DNA分析表明,在非洲,与Duffy抗原缺乏相关的所有物至少两次演变,并被强烈选用,导致其频率增加。Duffy基因只是许多具有多变异基因的基因之一,因为其中一个异性可以防止疟疾。 事实上,由于疟疾,已知的遗传多种形态可能比任何其他单一的选择性物剂都多。Factors Influencing the Level of Human Genetic Variation
::影响人类遗传变化程度的因素The age and size of a population increases the genetic variation within that population. You would expect an older, larger population to have more genetic variation. The older a population is, the longer it has been accumulating . The larger a population is, the more people there are in which mutations can occur. Anatomically modern humans evolved less than a quarter million years ago, which is a relatively short period of time for mutations to accumulate. Our population was also quite small at some point in the past, perhaps consisting of no more than ten thousand adults, which reduced genetic variation even more. These factors explain why humans are relatively homogeneous genetically as a species.
::人口的年龄和规模会增加该人口中的基因变异。你会期望一个年龄较大、人口较多的人口具有更多的基因变异。人口年龄越大,累积的时间越长。人口越多,发生突变的人就越多。现代人类的解剖学演化不到25万年前,是变异积累的相对较短的时期。我们的人口在过去的某个时候也相当小,可能不超过1万个成年人,从而降低了基因变异。这些因素解释了为什么人类作为一个物种具有相对单一的遗传特征。What We Can Learn From Knowledge of Human Genetic Variation
::我们能够从人类遗传变异知识中学习什么Knowledge of genetic variation can help us understand our similarities and differences, our origins, and our evolutionary past. It can also help us understand human diseases and — hopefully — find new ways to treat them.
::对基因变异的了解有助于我们了解我们的异同、起源和演变历史,也有助于我们了解人类疾病,并有希望找到治疗这些疾病的新方法。Human Origins
::人 原 人 源 人 源 人 源 人 源 人The data on human genetic variation generally supports the out-of-Africa hypothesis for human origins. According to this hypothesis, the common ancestor of all modern humans evolved in Africa around 200 thousand years ago. Then, starting no later than about 60 thousand years ago, part of the African population left Africa and migrated to Europe and Asia. As the migrants spread throughout the Old World, they replaced (and/or absorbed) the populations of archaic humans they encountered.
::人类基因变异数据一般支持非洲以外人类起源的假设。 根据这一假设,现代人类的共同祖先大约20万年前就在非洲演变了。 然后,从不晚于6万年前开始,部分非洲人口离开了非洲,移民到了欧洲和亚洲。 随着移民遍布整个老世界,他们取代(和(或)吸收)了他们所遇到的古老人类。Most studies of human genetic variation find there is greater genetic diversity in African than non-African populations. This is consistent with the older age of the African population proposed by the out-of-Africa hypothesis. In addition, most of the genetic variation in non-African populations is a subset of the variation in African populations. This is consistent with the idea that part of the African population left Africa much later and migrated to other places in the Old World.
::大多数人类基因变异研究发现,非洲人口的遗传多样性大于非洲以外的人口,这与非洲以外假设提出的非洲人口的老年年龄一致,此外,非洲以外的人口的大多数遗传变异是非洲人口变异的子集,这与非洲部分人口更晚离开非洲并迁移到老世界其他地方的想法是一致的。Recent comparisons of modern human and archaic human (including Neanderthal and Denisovan) DNA show that interbreeding occurred between their populations, but to differing degrees. The result of new DNA sequences entering a population’s gene pool through interbreeding is called admixture. There is greater admixture with archaic humans in modern European, Asian, and Oceanic populations than in modern African populations. Populations with the greatest admixture are those in Melanesia. About eight percent of their DNA came from archaic Denisovans in East Asia.
::最近对现代人类和古老人类(包括尼安德特人和杰尼索凡人)DNA的比较表明,他们之间的交织发生在人口之间,但程度不同。 新的DNA序列通过相互交织进入人口基因库的结果被称为粘合。 在现代欧洲、亚洲和海洋人口中,与古老人类的结合比在现代非洲人口中要大。 最混合的人口在美拉尼西亚。 大约8%的DNA来自东亚的古代杰尼索夫人。Human Population History
::人类人口史Patterns of human genetic variation can be used to reconstruct population history. That history is literally recorded in our DNA. Any major population event (such as a significant reduction in population size or a high rate of migration) leaves a mark on a population’s genetic variation.
::人类基因变异模式可以用来重建人口历史。 人类的基因变异模式可以用来重建人口历史。 历史实际上记录在我们的DNA中。 任何重大人口事件(如人口规模大幅缩小或高移民率)都会给人口的基因变异留下一个印记。-
Going through a dramatic size reduction decreases intra-population genetic variation (variation occurring within a population). As a case in point, DNA analyses suggest that there may have been drastic size reductions in the human populations that colonized the New World between 15 thousand and 20 thousand years ago. There were also size reductions in the human populations that first left Africa at least 60 thousand years ago, which helps explain the lower genetic diversity of modern non-African populations.
::通过大幅缩小人口规模,人口内部遗传变异(人口内部的变异)减少。 举例来说,DNA分析表明,在15 000至20 000年前殖民新世界的人类人口数量可能急剧减少。 在6 000年前首次离开非洲的人口数量也减少,这有助于解释现代非非洲人口的遗传多样性较低的原因。 -
A high rate of
between populations may lead to gene flow, and this changes genetic variation in two ways. Gene flow decreases inter-population genetic variation (variation occurring between populations), while it increases intra-population variation. Gene flow — primarily between nearby populations — may contribute to the formation of clines in allele frequencies, as on the map above.
::人口之间的高比率可能导致基因流动,这种基因变异以两种方式改变:基因流动减少人口之间的基因变异(人口之间的变异),同时增加人口内部的变异;基因流动——主要是附近人口之间的流动——可能有助于形成所有不同频率的线条,如上图所示。
Human Genetic Variation and Disease
::人类遗传变异和疾病An important benefit of studying human genetic variation is that we can learn more about the genetic basis of human diseases. The more we understand the causes of diseases, the more likely we will be able to find effective treatments and cures for them.
::研究人类基因变异的一个重要好处是我们可以更多地了解人类疾病的遗传基础,我们越了解疾病的原因,就越有可能找到有效的治疗和治疗方法。Some disorders are caused by mutations in a single gene. Most of these disorders are generally rare, but some of them occur at significantly higher frequencies in certain populations. For example, Ellis-van Creveld syndrome has an unusually high frequency in Pennsylvania Amish populations, and Tay-Sachs disease has a relatively high frequency in Ashkenazi Jewish populations. Albinism is another single-gene disorder that has a variable frequency. Only about one in every 17 thousand to 20 thousand people in North America and Europe have albinism. In Africa, in contrast, an estimated one in every five thousand to 15 thousand people have albinism. Some African populations have estimated albinism rates as high as one in one thousand. The photo shows an African albino man from Mali, where there is a relatively high rate of albinism. High population-specific frequencies of single-gene disorders like these may be attributable to a variety of factors, such as small founding populations and a relative lack of gene flow.
::某些疾病是由单一基因突变引起的,大多数这类疾病一般都是罕见的,但其中一些疾病在某些人口中发生频率要高得多。例如,艾利斯-凡·克雷维尔德综合症在宾夕法尼亚阿米什人中发病率异常高,而塔伊-萨赫斯疾病在阿什克纳齐犹太人人口中的发病率较高。白化病是另一个单一基因疾病,其频率不一。北美和欧洲每17 000至20 000人中只有一人患有白化病。相比之下,在非洲,估计每5 000至15 000人中就有一人患有白化病。一些非洲人口估计白化病发病率高达千分之一。照片显示,马里的非洲白化病患者患白化病的比例较高,那里患白化症的比例相对较高。这类单一基因疾病的高发频率可能与多种因素有关,如创始人口少和相对缺乏基因流动等。This man from Mali exhibits the lack of pigmentation that is a hallmark of albinism.
::这位来自马里的男子表现出缺乏色素,这是白化病的标志。It is likely that the majority of human diseases are caused by a complex mix of multiple genes (polygenic) and environmental factors (multifactorial). Examples of polygenic, multifactorial diseases are type II and heart disease. We do not typically think of these diseases as genetic diseases, because our genes do not predetermine whether we develop them. O ur genes, however, do influence our chances of developing the diseases under certain environmental conditions. Even our chances of developing some are influenced by our genes. For example, a variant allele for a gene called CCR5 seems to confer resistance to infection with , the that causes AIDS.
::大部分人类疾病很可能是由多种基因(多源基因)和环境因素(多因素因素)的复杂组合造成的,多源、多因子疾病的例子有第二类和心脏病。我们一般不把这些疾病视为遗传疾病,因为我们的基因并不预先决定我们是否发展这些疾病。然而,我们的基因确实影响到我们在某些环境条件下发展这些疾病的机会。即使我们发展一些疾病的机会也受到我们的基因的影响。例如,一种称为CCR5的基因的变异异异异基因似乎对艾滋病传染产生抵抗力。Summary
::摘要-
No two human individuals are genetically identical (except for monozygotic twins), but the human species as a whole exhibits relatively little genetic diversity, relative to other mammalian species. Genetically, two people chosen at random are likely to be 99.9 percent identical.
::与其他哺乳动物物种相比,人类的基因多样性相对较少。 在遗传学上,随机选择的两个人可能达到99.9%。 -
Of the total genetic variation in humans, about 90 percent occurs between people within continental populations. Only about 10 percent occurs between people from different continents. Older, larger populations tend to have greater genetic variation, because there is more time and there are more people in which to accumulate mutations.
::在人类的全部基因变异中,大约90%发生在大陆人口之间,只有大约10%发生在不同大陆的人之间。 年龄较大的人口往往有更大的基因变异,因为有更多的时间和更多的人可以积累突变。 -
Single nucleotide polymorphisms account for most human genetic differences. Allele frequencies for polymorphic genes generally have a clinal (rather than discrete) distribution. A minority of alleles seem to cluster in particular geographic areas, such as the allele for no antigen in the Duffy blood group. Such alleles may be useful as genetic markers to establish the ancestry of individuals.
::单核素化多形态的单一核素化是人类基因差异最大的因素。多形态基因的异变频率一般具有球形分布(而不是离散)分布。少数异变种似乎聚集在特定地理区域,如Duffy血族中无抗原的异变。这些异变可能作为基因标记,有助于确定个人的祖先。 -
Knowledge of genetic variation can help us understand our similarities and differences. It can also help us reconstruct our evolutionary origins and history as a species. For example, the distribution of modern human genetic variation is consistent with the out-of-Africa hypothesis for the origin of modern humans.
::基因变异的知识可以帮助我们理解我们的异同,也可以帮助我们重建我们作为一个物种的进化起源和历史。 比如,现代人类基因变异的分布符合非洲以外现代人类起源的假设。 -
An important benefit of studying human genetic variation is learning more about the genetic basis of human diseases. This, in turn, should help us find more effective treatments and cures.
::研究人类基因变异的一个重要好处是更多地了解人类疾病的遗传基础,这反过来又有助于我们找到更有效的治疗和治疗方法。
Review
::回顾1. Compare and contrast the significance of genetic variation at the individual and population levels.
::1. 比较和对比个人和人口层面遗传变异的重要性。2. Describe genetic variation within and between human populations on different continents.
::2. 描述不同大陆上人类人口内部和之间的基因变异。3. Explain why allele frequencies for the Duffy gene may be used as a genetic marker for African ancestry.
::3. 解释为什么Duffy基因的Allele频率可以用作非洲祖先的遗传标志。4. Identify factors that increase the level of genetic variation within populations.
::4. 查明提高人口内部遗传变异程度的因素。5. Discuss genetic evidence that supports the out-of-Africa hypothesis of modern human origins.
::5. 讨论支持非洲以外现代人类起源假设的遗传证据。6. What evidence suggests that modern humans interbred with archaic human populations after modern humans left Africa?
::6. 在现代人离开非洲之后,什么证据表明现代人与古老的人类人口交织在一起?7. How do population size reductions and gene flow impact the genetic variation of populations?
::7. 人口规模的缩小和基因流动如何影响人口的基因变异?8. Describe the role of genetic variation in human disease.
::8. 描述遗传变异在人类疾病中的作用。9. Explain the reasons why variation in a DNA sequence can have no effect on the fitness of an individual.
::9. 解释为什么DNA序列的变异不会对个人的健康状况产生影响的原因。10. Most human genetic differences...
::10. 大多数人类基因差异...a. are single nucleotide polymorphisms
::a. 是单核核酸多形态体b. occur between different continental populations
::b. 在不同大陆人口之间发生c. increase individual fitness
::c. 提高个人身体健康度d. decrease individual fitness
::d. 降低个人体格11. True or False: A person with an antigen in the Duffy blood group is unlikely to have recent African ancestry.
::11. 真实或假:在Duffy血族中有抗原的人不可能有最近的非洲血统。12. True or False: Most diseases are caused exclusively by genes.
::12. 真实或假:大多数疾病完全由基因引起的。13. Explain why migration between populations decreases inter-population genetic variation. How does this relate to the development of clines in allele frequency?
::13. 解释为什么人口之间的移徙会减少人口之间的基因变异,这与异频线的发展有何关系?14. The amount of mixing of modern human DNA and archaic human DNA is an example of _________ .
::14. 现代人类DNA和古老人类DNA的混合程度就是一例。Explore More
::探索更多Watch this TED talk to learn more about how knowledge of human genetic variation can be used to reconstruct our evolutionary past.
::观看TED的演讲, 学习更多关于人类基因变异的知识 如何用于重建我们进化的过去。Check out this video to learn more about albinism:
::校对:Portnoy -
Going through a dramatic size reduction decreases intra-population genetic variation (variation occurring within a population). As a case in point, DNA analyses suggest that there may have been drastic size reductions in the human populations that colonized the New World between 15 thousand and 20 thousand years ago. There were also size reductions in the human populations that first left Africa at least 60 thousand years ago, which helps explain the lower genetic diversity of modern non-African populations.
