Contribution of Mutation and RNA Recombination to the Evolution of a Plant Pathogenic RNA

The nucleotide sequence of 17 variants of the satellite RNA of cucumber mosaic virus (CMV-satRNA) isolated from field-infected tomato plants in the springs of 1989, 1990, and 1991 was determined. The sequence of each of the 17 satRNAs was unique and was between 334 and 340 nucleotides in length; 57 positions were polymorphic. There was much genetic divergence, ranging from 0.006 to 0.141 nucleotide substitutions per site for pairwise comparisons, and averaging 0.074 for any pair. When the polymorphic positions were analyzed relative to a secondary structure model proposed for CMV-satRNAs, it was found that there were significantly different numbers of changes in base-paired and non–base-paired positions, and that mutations that did not disrupt base pairing were preferred at the putatively paired sites. This supports the concept that the need to maintain a functional structure may limit genetic divergence of CMV-satRNA. Phylogenetic analyses showed that the 17 CMV-satRNA variants clustered into two subgroups, I and II, and evolutionary lines proceeding by the sequential accumulation of mutations were apparent. Three satRNA variants were outliers for these two phylogenetic groups. They were shown to be recombinants of subgroup I and II satRNAs by calculating phylogenies for different molecular regions and by using Sawyer's test for gene conversion. At least two recombination events were required to produce these three recombinant satRNAs. Thus, recombinants were found to be frequent (∼17%) in natural populations of CMV-satRNA, and recombination may make an important contribution to the generation of new variants. To our knowledge this is the first report of data allowing the frequency of recombinant isolates in natural populations of an RNA replicon to be estimated. Received: 14 May 1996 / Accepted: 17 July 1996     

Genetic exchange by recombination or reassortment is infrequent in natural populations of a tripartite RNA plant virus.

Two hundred seventeen field isolates of cucumber mosaic cucumovirus (CMV), sampled from 11 natural populations, were typed by RNase protection assay (RPA) using probes from the genomic RNAs of strains in subgroup I and in subgroup II of CMV strains. Most (85%) of the analyzed isolates belonged to subgroup I. For these subgroup I isolates, only two clearly different RPA patterns, A and B, were found for each of four probes representing RNA1, RNA2, and each of the two open reading frames in RNA3. On the basis of these RPA patterns for each probe, different haplotypes were defined. The frequency composition for these haplotypes differed for the various analyzed populations, with no correlation with place or year of sampling. This genetic structure corresponds to a metapopulation with local extinctions and recolonizations. Most subgroup I isolates (73%) belonged to haplotypes with RPA pattern A (type 1) or B (type 2) for all four probes. A significant fraction of subgroup I isolates (16%) gave evidence of mixed infections with these two main types, from which genetic exchange could occur. Genetic exchange by segment reassortment was seen to occur: the fraction of reassortant isolates was 4%, reassortment did not occur at random, and reassortants did not become established in the population. Thus, there is evidence of selection against reassortment between types 1 and 2 of subgroup I isolates. Aphid transmission experiments with plants doubly infected with type 1 and type 2 isolates gave further evidence that reassortment is selected against in CMV. Genetic exchange by recombination was detected for RNA3, for which two RPA probes were used. Recombinant isolates amounted to 7% and also did not become established in CMV populations. Sequence analyses of regions of RNA1, RNA2, and RNA3 showed that there are strong constraints to maintain the encoded sequence and also gave evidence that these constraints may have been different during divergence of types 1 and 2 and, later on, during diversification of these two types. Constraints to the evolution of encoded proteins may be related to selection against genetic exchange. Our data, thus, do not favor current hypotheses that explain the evolution of multipartite viral genomes to promote genetic exchange.     

Secondary structure as a constraint on the evolution of a plant viral satellite RNA.

The genetic variability and evolution of the satellite RNA (satRNA) of cucumber mosaic virus (CMV) was analyzed. Twenty-five CMV-satRNAs compared clustered into three main groups, and no correlation was found between genetic proximity and other characteristics (pathogenicity, geographical origin) of the satRNAs. Values for the number of nucleotide substitutions per site between any two satRNAs suggest that divergence is checked by functional constraints. The analysis of mutations relative to an ancestral sequence, and the number of substitutions per site at first, second and third positions of codons in putative open reading frames, show that the variation of CMV-satRNAs does not follow a pattern typical of coding sequences, and indicates that preservation of the sequence of encoded products is not a constraint to evolution. On the other hand, when the observed variation was analyzed relative to a secondary structure model proposed for CMV-satRNAs, several lines of evidence indicated that the maintenance of the secondary structure is a constraint to evolution: the number of substitutions per site, the number of point insertions and deletions and the number of base substitutions that would disrupt base-pairing were significantly higher for unpaired than for base-paired positions. Also, compensatory mutations at base-paired positions occurred more frequently than expected from random. The results suggest that CMV-satRNAs are non-coding, functional RNAs whose biology would be determined by their direct interaction with components of the host and/or the helper virus.     

Molecular population genetics of Cucumber mosaic virus in California: evidence for founder effects and reassortment

The structure and genetic diversity of a California Cucumber mosaic virus (CMV) population was assessed by single-strand conformation polymorphism and nucleotide sequence analyses of genomic regions 2b, CP, MP, and the 3' nontranslated region of RNA3. The California CMV population exhibited low genetic diversity and was composed of one to three predominant haplotypes and a large number of minor haplotypes for specific genomic regions. Extremely low diversity and close evolutionary relationships among isolates in a subpopulation suggested that founder effects might play a role in shaping the genetic structure. Phylogenetic analysis indicated a naturally occurring reassortant between subgroup IA and IB isolates and potential reassortants between subgroup IA isolates, suggesting that genetic exchange by reassortment contributed to the evolution of the California CMV population. Analysis of various population genetics parameters and distribution of synonymous and nonsynonymous mutations revealed that different coding regions and even different parts of coding regions were under different evolutionary constraints, including a short region of the 2b gene for which evidence suggests possible positive selection.     

Nucleotide diversity and Pleistocene population expansion in Atlantic and Mediterranean scallops (Pecten maximus and P. jacobaeus) as revealed by the mitochondrial 16S ribosomal RNA gene

Atlantic (Pecten maximus) and Mediterranean (Pecten jacobaeus) scallops have been traditionally considered as distinct species, but recent genetic studies have shown that they are races or subspecies separated by the Almeria-Oran oceanographic front in SE Spain. We have scored the nucleotide polymorphism of a 511 base pairs long fragment of the mitochondrial 16S ribosomal RNA gene in 85 individuals from 4 populations of P. maximus and 3 of P. jacobaeus. The populations were characterized by sharing the 2 most common haplotypes. We found no significant differences in haplotype frequencies among populations or species. However, slight, significant differentiation between taxa appeared when haplotypes were pooled in two groups according to their phylogenetic relationships and after analysis of molecular variance, in agreement with previous allozyme studies. Levels of within-population nucleotide diversity were similar in all populations except in P. jacobaeus from the northern Adriatic Sea, suggesting a smaller effective population size in that area which could be due to variable recruitment. Finally, populations showed an excess of rare haplotypes. The mismatch distribution and several population genetic statistics indicate that the excess of rare variants is due to a population expansion which occurred in the second half of the Pleistocene period, less than 0.9 my before present, and probably well after the origin of the two scallop races.     

Linkage disequilibrium and the mapping of complex human traits.

The potential value of haplotypes defined by several single nucleotide polymorphisms has attracted recent interest. With sufficient linkage disequilibrium (LD), haplotypes could be used in association studies to map common alleles that might influence the susceptibility to common diseases, as well as for reconstructing the evolution of the genome. It has been proposed that a globally useful resource need only be based on high frequency variants, identified from a few modest samples. Rapid progress has been made in quantifying the pattern of human LD and haplotypes defined by such common variants within and among populations. However, the quality and utility of the proposed LD-based resource could be seriously compromised if important sampling and analytical factors are overlooked in its design. The LD map should be based on adequately justified criteria defined by sound population genetic principles.     

中国对虾16 S rRNA基因序列多态性的研究

利用ＰＣＲ技术扩增获得中国对虾（Ｐｅｎａｅｕｓ ｃｈｉｎｅｎｓｉｓ）线粒体ＤＮＡ的１６Ｓ ｒＲＮＡ基因片段,通过测定该基因片段的序列,分析了取自我国烟台、长岛近海和宁波养殖的１７只中国对虾遗传多态性。结果发现,不同地理种群存在丰富的ＤＮＡ序列多态性,１７只个体具有１７种基因型,在扩增的长为５２３ｂｐ的基因片段中,共检测到３７个多态性核苷酸位点（７．０７％）。ＵＰＧＭＡ法构建的分子系统树表明不同地理     

The evolution of virulence in a plant virus

Abstract The evolution of virulence is a rapidly growing field of research, but few reports deal with the evolution of virulence in natural populations of parasites. We present here an observational and experimental analysis of the evolution of virulence of the plant virus Cucumber mosaic virus (CMV) during an epidemic on tomato in eastern Spain. Three types of CMV isolates were found that caused in tomato plants either a systemic necrosis (N isolates), stunting and a severe reduction of leaf lamina (Y isolates), or stunting and leaf curl (A isolates). These phenotypes were due to the presence of satellite RNAs (satRNAs) necrogenic (in N isolates) or attenuative (in A isolates) of the symptoms caused by CMV without satRNA (Y isolates). For these three types of isolates, parameters of virulence and transmission were estimated experimentally. For virulence the ranking of isolates was N < Y < A, for trans-missibility, Y < A < N. The predictions of theoretical models for the evolution of virulence were analyzed with these parameters and compared with observations from the field. A single-infection model predicted adequately the observed long-term evolution of the CMV population to intermediate levels of virulence. A coinfection model that considered competition between isolates with an effect on transmission explained the invasion of the CMV population by N isolates at the beginning of the epidemic, and its predictions also agreed with field data on the long-term evolution of the CMV population. An important conclusion from both models was that the density of the aphid vector's population is a major factor in the evolution of CMV virulence. This may be relevant for the design of control strategies for CMV-induced diseases.     

Cloning and genetic variability of a HindIII repetitive DNA in Acrossocheilus paradoxus (Cyprinidae).

Thirty clones of a highly repetitive HindIII fragment of DNA from seven populations of Acrossocheilus paradoxus (Cyprinidae) were isolated and sequenced. The fragment represents a tandemly repeated sequence, with a monomeric unit of 270 bp, amounting to 0.08-0.10% of the fish genome. Higher units of this monomer appear as a ladder in Southern blots. The HindIII satellite DNA family is conserved in three genera of the Cyprinidae. Variation in nucleotide sequences of this repetitive fragment, which is A+T-rich, is distributed both within individuals and among populations. High overall nucleotide divergence (dij = 0.056 +/- 0.001) was detected among clones of the HindIII satellite DNAs of Acrossocheilus paradoxus. Based on the molecular clock hypothesis, the maximum evolutionary rate was estimated to be 5.3 x 10(-7) substitutions per site per year. Lineage sorting may have contributed to the genetic heterogeneity within individuals and populations. Cladistic analyses indicated a closer phylogeographic relationship between populations of the central and south regions in Taiwan.     

基于叶绿体单倍型的山东丹参居群遗传结构分析

依据叶绿体psbA-trnH基因间隔区的序列多态对来自山东地区丹参的3个自然居群和1个栽培居群进行了遗传结构研究.结果显示,80个供试材料中共有10种单倍型,核苷酸多样性为0.024,叶绿体DNA单倍型进化分支分析把10种单倍型分为2大支,但每支都由4个居群的单倍型共同构成;Nei多样性指数为0.284,Shannon信息指数为0.406,多态位点百分比率为70%;4个居群总基因多样性为0.905,居群内平均基因多样性指数为0.747,遗传分化系数为0.175;不同居群间的遗传分化系数为0.017～0.199,基因流为2.013～28.912;AMOVA分析揭示居群间只有5%的遗传差异.研究结果表明,山东丹参遗传多样性水平较高,但由于彼此较高的基因交流,居群间遗传分化水平低,仅有的遗传差异主要存在于居群内;另外,序列谱系关系分析表明山东栽培丹参来源复杂且具有丰富的遗传多样性.     

The linkage disequilibrium between chloroplast DNA and mitochondrial DNA haplotypes in Beta vulgaris ssp. maritima (L.): the usefulness of both genomes for population genetic studies

The structure and evolution of the plant mitochondrial genome may allow recurrent appearance of the same mitochondrial variants in different populations. Whether the same mitochondrial variant is distributed by migration or appears recurrently by mutation (creating homoplasy) in different populations is an important question with regard to the use of these markers for population genetic analyses. The genetic association observed between chloroplasts and mitochondria (i.e. two maternally inherited cytoplasmic genomes) may indicate whether or not homoplasy occurs in the mitochondrial genome. Four-hundred and fourteen individuals sampled in wild populations of beets from France and Spain were screened for their mitochondrial and chloroplast polymorphisms. Mitochondrial DNA (mtDNA) polymorphism was investigated with restriction fragment length polymorphism (RFLP) and chloroplast DNA (cpDNA) polymorphism was investigated with polymerase chain reaction PCR-RFLP, using universal primers for the amplification. Twenty and 13 variants for mtDNA and cpDNA were observed, respectively. Most exhibited a widespread geographical distribution. As a very strong linkage disequilibrium was estimated between mtDNA and cpDNA haplotypes, a high rate of recurrent mutation was excluded for the mitochondrial genome of beets. Identical mitochondrial variants found in populations of different regions probably occurred as a result of migration. We concluded from this study that mtDNA is a tool as valuable as cpDNA when a maternal marker is needed for population genetics analyses in beet on a large regional scale.     

Low mtDNA Cytb diversity and shallow population structure of Eleutheronema tetradactylum in the East China Sea and the South China Sea

Eleutheronema tetradactylum is an economically important fish species in China water. To investigate the genetic diversity and describe population structure of it, an 1151 base pair (bp) fragment of the mitochondrial DNA Cytb sequence was analyzed in 120 individuals from four populations in the East China Sea and the South China Sea. A total of 16 haplotypes were defined by 24 variable nucleotide sites. High level of haplotype diversity and low nucleotide diversity were observed in all populations. The results of AMOVA detected that 89.44% of the genetic variation occurred within populations. Significant genetic differentiations were detected among populations (0.05097, P < 0.05), but no large-scale regional differences were detected. Analysis of neutral evolution and mismatch distribution suggested no recent population expansion happened. The present results provided new information for genetic assessment, fishery management and conservation of this species.     

Genetic variation in populations of the endangered fish Ladigesocypris ghigii and its implications for conservation

1. The genetic variation of the endangered freshwater fish Ladigesocypris ghigii, endemic to the island of Rhodes (Greece), was investigated for nine populations, originating from seven different stream systems and a reservoir, both at the mtDNA and nuclear level, in order to suggest conservation actions. 2. Both restriction fragment length polymorphism analysis of five segments of mitochondrial DNA (ND‐5/6, COI and 12S‐16S rRNA) amplified by polymerase chain reaction, and random amplified polymorphic DNA analysis, revealed extremely low levels of intra‐population polymorphism. It is highly likely that the low intra‐population variability is the result of successive bottleneck events evident in shrinkage and expansion of the populations year after year, which may have led to a complete loss of several genotypes and haplotypes, and an increased degree of inbreeding. 3. Inter‐population genetic structuring was high, with fixation of haplotypes within six of the nine populations and fixation of alleles within populations originating from different waterbodies. It is probable that all haplotypes and/or alleles found were initially represented in all populations. However, because of the long time of isolation coupled with successive bottleneck and subsequent genetic drift, common mtDNA haplotypes and alleles among the populations may have become rare or extinct through stochastic lineage loss. 4. Although nucleotide divergence among haplotypes was very shallow, half of the haplotypes recorded (three of six), resulted from nucleotide changes on the 12S–16S rRNA segments, which are the most conserved part of the mitochondrial genome. This fact may indicate that the observed genetic variation did not necessarily result only from the retention of ancestral polymorphism, but may have arisen through mutation and complete lineage sorting over a relatively small number of generations, once the populations had become isolated from one another. 5. Our data suggest that two of the L. ghigii populations may be on independent evolutionary trajectories. Considering that each population appears so far well adapted within each site, all populations should be managed and conserved separately.     

Genetic Variation Analysis of Mugil cephalus in China Sea Based on Mitochondrial COI Gene Sequences

In this study, genetic diversity and population genetic structure of flathead grey mullet, Mugil cephalus, among four China Sea populations were investigated by COI sequences. All the populations studied had high values of haplotype and nucleotide diversity, except for the Yellow Sea population. In the phylogenetic tree, these haplotypes clustered in two groups, one for the populations from the Bohai and East China seas, and the other from the Yellow and South China seas. Analysis of molecular variance indicated that the northern populations (Bohai and East China) had lower genetic divergence (0.0725, P > 0.05) than that of the southern population (South China) (0.4530-0.6827, P < 0.001), suggesting that two distinct genetic groups exist in Chinese waters. Tests of neutral evolution and mismatch distribution indicated that no historical demographic expansion occurred in these populations. The results provide new information for genetic assessment, fishery management, and conservation of this species.     

Distribution of genetic variation in the growth hormone 1 gene in Atlantic salmon (Salmo salar) populations from Europe and North America

The level and hierarchical distribution of genetic variation in complete sequences of the Atlantic salmon (Salmo salar) growth hormone (GH1) gene were investigated in populations from Europe and North America with a view to inferring the major evolutionary forces affecting genetic variation at this locus. Seventeen polymorphic sites were identified in complete sequences from nine populations, with levels of noncoding (intron and untranslated region sequences) nucleotide diversity being similar to those observed in other species. No variation, however, was observed in exonic sequences, indicating that nucleotide diversity in the Atlantic salmon GH1 gene is three and 25 times less than that estimated for human and Drosophila coding sequences, respectively. This suggests that purifying selection is the predominant contemporary force controlling the molecular evolution of GH1 coding sequences. Comparison of haplotype relationships within and between populations indicated that differentiation between populations from Europe and North America was greater than within-continent comparisons. However, several haplotypes observed in the northernmost European populations were more similar to those observed in North American than to any other haplotypes observed in Europe. This is most likely to be a result of historical, rather than contemporary, gene flow. Neutrality test statistics, such as Tajima's D, were significantly positive in the European populations in which North American-like haplotypes were observed. Although a positive Tajima's D is commonly interpreted as the signal of balancing selection, a more likely explanation in this case is that either historical migration or ascertainment bias, rather than within population local adaptation, has given rise to an excess of intermediate frequency alleles.     

Phylogeography and population structure of the golden monkeys (Rhinopithecus roxellana): inferred from mitochondrial DNA sequences

The golden monkey (Rhinopithecus roxellana) is one of the most endangered primate species due to its dramatically shrinking distribution during the past 400 years. Its populations are restricted to three isolated regions, Qinglin (QL), Sichuan/Gansu (SG), and Shennongjia (SNJ) in China. As with other snub-nosed monkeys in China and Vietnam, the biology and evolution of this species is still poorly known. To assess genetic differentiation and explore the relationships among populations of golden monkeys from different geographic locations, 379 bp of mitochondrial DNA control region (CR) hypervariable segment I (HVI) was studied from 60 individuals. Twelve haplotypes were identified from seven populations within the three regions. Haplotype diversity was high (0.845), whereas nucleotide diversity among all haplotypes was low (0.0331). The most recent common ancestor (TMRCA) among mtDNA haplotypes was estimated to have lived approximately 0.48-0.32 million years ago. None of the haplotypes is shared among any of the three regions. Phylogenetic analysis and AMOVA revealed clear and significant phylogeographic structure between the three regions. However, only SG contained haplotypes of the two main clades, indicating either incomplete random sorting of haplotypes or a complex history with phases of population subdivisions and merging of populations. The phylogeographic structure implies that R. roxellana should be regarded as separate management units (MUs) for each of the three regions. It is likely that recent phylogeographic history has shaped the pattern of genetic differentiation observed in the golden monkey and that its populations have suffered significant demographic fluctuation.     

Estimation of the effective number of founders that initiate an infection after aphid transmission of a multipartite plant virus

The fecundity of RNA viruses can be very high. Thus, it is often assumed that viruses have large populations, and RNA virus evolution has been mostly explained using purely deterministic models. However, population bottlenecks during the virus life cycle could result in effective population numbers being much smaller than reported censuses, and random genetic drift could be important in virus evolution. A step at which population bottlenecks may be severe is host-to-host transmission. We report here an estimate of the size of the population that starts a new infection when Cucumber mosaic virus (CMV) is transmitted by the aphid Aphis gossypii, based on the segregation of two CMV genotypes in plants infected by aphids that acquired the virus from plants infected by both genotypes. Results show very small effective numbers of founders, between one and two, both in experiments in which the three-partite genome of CMV was aphid transmitted and in experiments in which a fourth RNA, CMV satellite RNA, was also transmitted. These numbers are very similar to those published for Potato virus Y, which has a monopartite genome and is transmitted by aphids according to a different mechanism than CMV. Thus, the number of genomic segments seems not to be a major determinant of the effective number of founders. Also, our results suggest that the occurrence of severe bottlenecks during horizontal transmission is general for viruses nonpersistently transmitted by aphids, indicating that random genetic drift should be considered when modeling virus evolution.     

基于线粒体COⅠ和16S rRNA基因序列比较分析东海带鱼群体遗传多样性

测定了东海带鱼(Trichiurus lepturus Linnaeus)三个群体(命名为A: 122°32′E 29°55′N、B: 123°30′E 26°75N; C: 124°24′E 27°26′N)72个个体的线粒体DNA16S rRNA和COⅠ基因序列,通过单基因序列和联合序列分析, 研究了东海带鱼群体的遗传变异情况。分别得到1130 bp的COⅠ基因序列片段和554 bp的16S rRNA序列片段, 其中COⅠ基因片段的T、C、A、G含量分别为29.0%、28.9%、24.4%和17.7%; 16S rRNA基因片段的T、C、A、G含量分别为22.7%、27.6%、28.0%和21.7%。基于线粒体16S rRNA、COⅠ和16S+COⅠ基因序列分析, 72个个体中分别确定43个, 8个和49个单倍型, 存在单倍型共享现象。群体的单倍型多样性指数为0.9766—0.9992, 显示了群体内的单倍型较为丰富。3个群体间各序列平均核苷酸差异数(K)在5.111—9.024和0.0045—0.0076, 核苷酸多样性指数(π)为0.0048—0.0084, 显示不同带鱼群体遗传多态性丰富。使用邻接法构建的分子进化树揭示同一群体内大部分个体聚在一起。分析结果表明, 群体A遗传背景比群体B、群体C较为丰富, 群体内部个体差异大于群体间差异, 群体间基因交流频率较高, 遗传分化不明显, 初步判定东海带鱼3个群体的遗传多样性偏低。     

西藏牦牛线粒体DNA 的遗传多样性及系统进化分析

为从分子水平上探究西藏牦牛类群的遗传多样性、亲缘关系,本研究测定了日多牦牛、类乌齐牦牛、丁青牦牛、错那牦牛、隆子牦牛、仲巴牦牛、聂荣牦牛、申札牦牛等8 个西藏牦牛类群共328 头牦牛mtDNAD-loop区序列,分析其多态性,构建系统进化树。结果表明:本次测定的西藏牦牛mtDNA D-loop 区序列长度为 887 - 895 bp,共检测到135 个变异位点,其中单态突变位点52 个,简约信息位点83 个。在328 个个体中共检测出91 种单倍型,平均单倍型多样性(Hd)、平均核苷酸多样性(π)分别为0. 884、0.010 27,显示西藏牦牛具有丰富的遗传多样性。8 个类群间平均遗传距离为0.011;日多牦牛与错那牦牛间遗传距离最小(0. 006);类乌 齐牦牛与隆子牦牛间遗传距离最大(0.015)。系统进化分析显示西藏牦牛可分为两大类,错那牦牛是较纯的牦牛类群,其它牦牛类群在进化过程中出现相互交流的情况。     

Haplotypes That Are Mosaic for Wild-Type and T Complex-Specific Alleles in Wild Mice

Two outstanding problems pertaining to the population dynamics and evolution of the t complex in mice concern the frequency of t haplotypes in the wild and the degree to which these haplotypes recombine with their wild-type homologs. To address these problems, the frequency and distribution of several t complex-associated restriction fragment variants in wild mice were estimated. Sixty-four versions of chromosome 17 from wild-derived Mus musculus musculus and Mus musculus domesticus were examined with DNA probes for six loci within the t complex that exhibit restriction fragment variation. All six probes detect variants that have heretofore been found exclusively associated with the t complex. Haplotype analysis of wild-derived chromosomes revealed a high frequency (45.3%) of "mosaic" haplotypes with a mixture of t-specific and wild-type variants and only one haplotype with t-specific variants at all six loci. When 12 well-characterized t haplotypes isolated from diverse geographic regions were analyzed, only three had a complete set of t-specific restriction fragments for the six loci examined. The preponderance of mosaic haplotypes in both groups of mice can be explained by any one of the following hypotheses: genetic recombination between t haplotypes and their wild-type homologs, the persistence in wild populations of haplotypes that have descended from ancestral partial t haplotypes, or that the restriction fragment variants fixed in the ancestral t haplotype were also fixed in some wild-type haplotypes. There is evidence to support all three of these hypotheses in our data. The allelic composition of some mosaic haplotypes indicates that they may have been formed by segmental recombination, either double crossing over or gene conversion, rather than by simple single crossovers. The occurrence of indistinguishable mosaic haplotypes in both M. m. musculus and M. m. domesticus suggests that these haplotypes are ancestral rather than recently derived.