Molecular Biological Study of Chemokine Gene Family

趋化因子是一类小的细胞因子家族，在各种类型的白细胞的定向迁移中发挥重要作用。根据保守的半胱氨酸残基的排列，它们被划分为两个主要的亚家族CXC和CC，以及两个次要的亚家族C和CX3C。到目前为止，在人类中已经鉴定出该家族的40多个成员。值得注意的是，CXC趋化因子基因和CC趋化因子基因主要集中在染色体4q12-21和17q11.2。同样，小鼠主要的CXC和CC趋化因子基因簇分别位于5号和11号染色体上。为了了解在各自的染色体上产生大量CXC和CC趋化因子基因的进化过程，我们构建了覆盖人类和小鼠主要CXC和CC趋化因子基因簇的BAC和YAC重叠群。结果表明，CXC和CC趋化因子基因在主要簇中的组织在两个物种之间存在很大差异，最可能的原因是最近的基因复制和重排。我们的结果为了解产生主要趋化因子基因簇的进化过程提供了重要的见解，也为确定人类和小鼠主要趋化因子簇之间的同源基因提供了有价值的信息。

Chemokines are a family of small cytokines that play essential roles in the directed migration of various types of leukocytes. Based on the arrangement of the conserved cysteine residues, they are classified into two major subfamilies, CXC and CC, and two minor subfamilies, C and CX_3C.So far, more than 40 members of this family have been identified in humans. Strikingly, the majority of CXC chemokine genes and that of CC chemokine genes are closely clustered at chromosomes 4q 12-21 and 17q11.2, respectively. Similarly, the mouse major CXC and CC chemokine gene clusters are located on chromosomes 5 and 11, respectively. In order to understand the evolutionary processes that generated large numbers of CXC and CC chemokine genes in the respective chromosomal sites, we have constructed BAC and YAC contigs covering the human and mouse major clusters of CXC and CC chemokine genes. The results reveal that the organizations of CXC and CC chemokine genes in the major clusters are quite diverged between the two species most probably due to very recent gene duplications and rearrangements. Our results provide an important insight into the evolutionary processes that generated the major chemokine gene clusters and also valuable information in assigning the orthologues between human and mouse major cluster chemokines.