Increased heterozygosity for MHC class II lineages in newborn males
Increased heterozygosity for MHC class II lineages in newborn males
复制标题
DOI：
10.1038/sj.gene.6363862
复制
发表时间：
2002-08-01
影响因子：
5
通讯作者：
Burnett, AK
中科院分区：
文献类型：
--
作者：
Dorak, MT;Lawson, T;Burnett, AK
在植物、真菌和海洋无脊椎动物中，存在遗传相容性系统以确保后代的多样性。遗传相容性在脊椎动物配子结合和选择性流产中的重要性最近也受到重视。有人认为主要组织相容性复合体（人类HLA）可能是脊椎动物的相容性系统。HLA II类单倍型通常含有第二个表达的DRB基因座，其可以是DRB 3、DRB 4或DRB 5。这些编码的超典型的特异性和标记的祖先血统。每个谱系的成员在主要的II类基因座HLA-DRB 1处具有相关的DNA序列。我们分析了415名新生儿在所有表达DRB基因座的PCR分析，以寻求性别特异性产前选择事件的证据。虽然在DRB 1时男性和女性之间的杂合率没有显著变化，但携带来自不同祖先谱系的两种DRB 1特异性的男性比例显著增加（男性53.7% vs女性39.3%，P= 0.003）。性别间差异最显著的是DRB 3和DRB 4单倍型，其中DRB 3和DRB 4单倍型的基因型差异最显著（P= 0.007）。这些结果表明，对于超典型单倍型杂合的男性孕体来说，结果更有利。大多数不同单倍型家族的杂合性确保了主要HLA 11类基因座DRB 1处的最高程度的功能杂合性，同时也增加了其他MHC基因座处杂合性的可能性。我们的观察结果与先前报道的雄性新生大鼠和小鼠中杂合子过量一致。MHC II类杂合性和广告的男性质量之间的相关性，鹿和野鸡，以及增加繁殖成功的MHC II类杂合雄性猕猴的出生后的好处，在男性的杂合性，可能是背后的产前选择机制的发展的例子。MHC介导的男性产前选择也可能是选择性事件之一，这是由受精时的初级（男性对女性）性别比非常高而在人类出生时接近1所暗示的。这些结果为人类和其他脊椎动物的进一步研究提供了一个有吸引力的工作假设。
In plants, fungi and marine invertebrates, there are genetic compatibility systems to ensure diversity in the offspring. The importance of genetic compatibility in gametic union and selective abortion in vertebrate animals has also been appreciated recently. There have been suggestions that the major histocompatibility complex (HLA in humans) may be a compatibility system in vertebrates. HLA class II haplotypes often contain a second expressed DRB locus which can be either DRB3, DRB4 or DRB5. These encode the supertypical specificities and mark the ancestral lineages. The members of each lineage have related DNA sequences at the main class II locus HLA-DRB1. We analysed 415 newborns at all expressed DRB loci by PCR analysis to seek evidence for sex-specific prenatal selection events. While there was no significant change in heterozygosity rates between males and females at DRB1, the proportion of males carrying two DRB1 specificities from different ancestral lineages was significantly increased (53.7% in males vs 39.3% in females, P= 0.003). The genotypes consisting of phylogenetically most distinct ones, namely the DRB3 and DRB4 haplotypes, showed the most striking difference between sexes (P= 0.007). These results suggested a more favourable outcome for male concepti heterozygous for supertypical haplotypes. Heterozygosity for most divergent haplotypical families ensures the highest degree of functional heterozygosity at the main HLA class 11 locus DRB1 while increasing the likelihood of heterozygosity also at other MHC loci. Our observations agree with the previously reported heterozygote excess in male newborn rats and mice. Correlations between MHC class II heterozygosity and advertised male quality in deer and pheasant as well as increased reproductive success in MHC class II heterozygous male macaques are examples of postnatal benefits of heterozygosity in males that may be behind the development of prenatal selection mechanisms. The MHC-mediated prenatal selection of males may also be one of the selective events suggested by the very high primary (male-to-female) sex ratio at fertilization reaching close to unity at birth in humans. These results provide an appealing working hypothesis for further studies in humans and other vertebrates.