Alu fossil relics--distribution and insertion polymorphism.

130

139

The insertion of mobile elements into the genome represents a new class of genetic markers for the study of human evolution. Long interspersed elements (LINEs) have amplified to a copy number of about 100,000 over the last 100 million years of mammalian evolution and comprise ∼15% of the human genome. The majority of LINE-1 (L1) elements within the human genome are 5Ј truncated copies of a few active L1 elements that are capable of retrotransposition. Some of the young L1 elements have inserted into the human genome so recently that populations are polymorphic for the presence of an L1 element at a particular chromosomal location. L1 insertion polymorphisms offer several advantages over other types of polymorphisms for human evolution studies. First, they are typed by rapid, simple, polymerase chain reaction (PCR)-based assays. Second, they are stable polymorphisms that rarely undergo deletion. Third, the presence of an L1 element represents identity by descent, because the probability is negligible that two different young L1 repeats would integrate independently between the exact same two nucleotides. Fourth, the ancestral state of L1 insertion polymorphisms is known to be the absence of the L1 element, which can be used to root plots/trees of population relationships. Here we report the development of a PCR-based display for the direct identification of dimorphic L1 elements from the human genome. We have also developed PCR-based assays for the characterization of six polymorphic L1 elements within the human genome. PCR analysis of human/rodent hybrid cell line DNA samples showed that the polymorphic L1 elements were located on several different chromosomes. Phylogenetic analysis of nonhuman primate DNA samples showed that all of the recently integrated "young" L1 elements were restricted to the human genome and absent from the genomes of nonhuman primates. Analysis of a diverse array of human populations showed that the allele frequencies and level of heterozygosity for each of the L1 elements was variable. Polymorphic L1 elements represent a new source of identical-by-descent variation for the study of human evolution.

Section: Discussionsupporting

confidence: 70%

Reading between the LINEs: Human Genomic Variation Induced by LINE-1 Retrotransposition

Sheen¹,

Sherry²,

Risch³

et al. 2000

130

139

“…phic loci will be biased (Tachida and Iizuka 1993). Random screening of human-specific Alu elements indicates that ∼20% are polymorphic (Arcot et al 1996); hence, we estimate that for the 8 polymorphic loci in our study, we need to include 32 monomorphic loci in the genetic distance calculation. The resulting average genetic distance between African and non-African populations is 0.0246, which from equation 33 of Tachida and Iizuka (1993) corresponds to an effective separation time of 137,000 ‫ע‬ 15,000 years ago.…”

Section: Figurementioning

confidence: 99%

“…Be-cause both the Ya5 and Ya8 Alu subfamilies share a number of diagnostic mutations we refer to this lineage collectively as Ya5/8 . The Ya5/8 Alu subfamily lineage is comprised of 500-2000 elements that are restricted to the human genome (Arcot et al 1996), although a few Ya5 Alu family members have been found in chimpanzees (for review, see Deininger and Batzer 1995). In parallel, a second subfamily that is an independent derivative of the Y lineage of Alu sequences, termed Yb8, has also expanded to ∼500 copies within the human genome (Batzer et al 1995(Batzer et al , 1996a.…”

mentioning

confidence: 99%

AluInsertion Polymorphisms and Human Evolution: Evidence for a Larger Population Size in Africa

Stoneking

Fontius²,

Clifford³

et al. 1997

286

247

Alu insertion polymorphisms (polymorphisms consisting of the presence/absence of an Alu element at a particular chromosomal location) offer several advantages over other nuclear DNA polymorphisms for human evolution studies. First, they are typed by rapid, simple, PCR-based assays; second, they are stable polymorphisms-newly inserted Alu elements rarely undergo deletion; third, the presence of an Alu element represents identity by descent-the probability that different Alu elements would independently insert into the exact same chromosomal location is negligible; and fourth, the ancestral state is known with certainty to be the absence of an Alu element. We report here a study of 8 loci in 1500 individuals from 34 worldwide populations. African populations exhibit the most between-population differentiation, and the population tree is rooted in Africa; moreover, the estimated effective time of separation of African versus non-African populations is 137,000 ± 15,000 years ago, in accordance with other genetic data. However, a principal coordinates analysis indicates that populations from Sahul (Australia and New Guinea) are nearly as close to the hypothetical ancestor as are African populations, suggesting that there was an early expansion of tropical populations of our species. An analysis of heterozygosity versus genetic distance suggests that African populations have had a larger effective population size than non-African populations. Overall, these results support the African origin of modern humans in that an earlier expansion of the ancestors of African populations is indicated.The Alu family of short interspersed elements is one of the most successful mobile genetic elements, having arisen to a copy number in excess of 500,000 within primate genomes in the last 65 million years (for recent reviews, see Okada 1991;Schmid and Maraia 1992; Batzer 1993, 1995). Alu repeats are thought to be ancestrally derived from the 7SL RNA gene and mobilize through an RNA polymerase III-derived transcript in a process termed retroposition. Each Alu sequence is ∼300bp in length; therefore, Alu repeats comprise ∼5% of the human genome.Alu sequences can be divided into different subfamilies or clades of related elements based on commonly shared diagnostic mutations. Here, we use the new standardized nomenclature to refer to various Alu subfamilies (Batzer et al. 1996a). Two of the most recently formed subfamilies of Alu elements within the human genome have been termed Ya5 and Ya8 (Batzer et al. 1990;. Members of the Ya8 Alu subfamily are characterized by all five of the Ya5 diagnostic mutations, as well as three additional diagnostic mutations. Be- GENOME RESEARCH 1061Cold Spring Harbor Laboratory Press on May 12, 2018 -Published by genome.cshlp.org Downloaded from cause both the Ya5 and Ya8 Alu subfamilies share a number of diagnostic mutations we refer to this lineage collectively as Ya5/8 (Batzer et al. 1996b). The Ya5/8 Alu subfamily lineage is comprised of 500-2000 elements that are restricted to the human genome (Arco...

“…PCR products were directly visualized using UV fluorescence. The sequences of the oligonucleotide primers, annealing temperatures, PCR product sizes, and chromosomal locations for the loci have been reported previously (Arcot et al 1996(Arcot et al , 1998Stoneking et al 1997). …”

Section: Dna Samples and Alu Genotypingmentioning

confidence: 99%

Patterns of Human Diversity, within and among Continents, Inferred from Biallelic DNA Polymorphisms

Romualdi¹,

Balding²,

Nasidze³

et al. 2002

199

123

Previous studies have reported that about 85% of human diversity at Short Tandem Repeat (STR) and Restriction Fragment Length Polymorphism (RFLP) autosomal loci is due to differences between individuals of the same population, whereas differences among continental groups account for only 10% of the overall genetic variance. These findings conflict with popular notions of distinct and relatively homogeneous human races, and may also call into question the apparent usefulness of ethnic classification in, for example, medical diagnostics. Here, we present new data on 21 Alu insertions in 32 populations. We analyze these data along with three other large, globally dispersed data sets consisting of apparently neutral biallelic nuclear markers, as well as with a ␤-globin data set possibly subject to selection. We confirm the previous results for the autosomal data, and find a higher diversity among continents for Y-chromosome loci. We also extend the analyses to address two questions: (1) whether differences between continental groups, although small, are nevertheless large enough to confidently assign individuals to their continent on the basis of their genotypes; (2) whether the observed genotypes naturally cluster into continental or population groups when the sample source location is ignored. Using a range of statistical methods, we show that classification errors are at best around 30% for autosomal biallelic polymorphisms and 27% for the Y chromosome. Two data sets suggest the existence of three and four major groups of genotypes worldwide, respectively, and the two groupings are inconsistent. These results suggest that, at random biallelic loci, there is little evidence, if any, of a clear subdivision of humans into biologically defined groups.In various areas of applied genetics, it is customary to regard the human species as divided in distinct and objectively recognizable groups. Forensic scientists compare DNA profiles from the place of a crime with databases from the general population, usually grouped into broad racial categories (for instance, African-American, European-American, Asian, and Hispanic), to estimate the probability that an unrelated individual would have the identical DNA profile. The markers chosen for DNA profiling are considered to be essentially uniform across populations of the same category. Although the existence of problems with group definition has been acknowledged (e.g., Weir 2001), the fact that some individuals may not be easy to allocate to any such group is usually regarded as unimportant (National Research Council 1992;Lander and Budowle 1994;Morton 1994;Roeder 1994;Gill and Evett 1995). In clinical practice, a correlation of racial affiliation, as assessed from skin color, facial characteristics, hair texture, and so forth, with disease pathology and drug response is widely believed to exist. A PubMed search with the keywords "human races" (January 10, 2002) In contrast, population studies have suggested that genetic variation is essentially continuous through space amon...